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Treating pediatric acute promyelocytic leukemia in india – key challenges and lessons learned
No full textAcute promyelocytic leukemia (APML) is an uncommon subtype of acute myeloid leukemia (AML) among children with scarce literature available on treatment outcomes. In this regard, the recent article by Srinivasan et al. published in IJP presents important data on the outcome of pediatric APML treated at a tertiary care centre in India [1]. APML is known to be uniquely sensitive to differentiating agents like all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). The use of ATO in APML has been derived from research conducted based on the traditional knowledge of Chinese medicine. This is one of the examples which highlights how knowledge derived from traditional and complementary medicine may augment modern healthcare research. Systematic and rigorous studies on traditional remedies may open up newer options of treatment in medicine. Indeed, the coronavirus disease-19 pandemic offered a unique situation when research on traditional and complementary medicine was extensively conducted in countries like India and China [2].
Chemotherapy free regimens are often emphasized as the way forward in APML at least in low-risk disease, unlike the traditional chemotherapy-based regimens for AML which use anthracyclines, cytosine arabinoside and/or etoposide [3]. In this study, the authors used ATRA and ATO alternatively along with oral and intravenous chemotherapeutic agents, with uniform use of steroids prophylactically during induction to prevent differentiation syndrome. Even then, the results show that nearly 40% of the children did require anthracyclines as cytoreductive therapy due to the differentiation syndrome. Additionally, the requirement of cytoreductive therapy was expectedly significantly higher (81%) in high-risk disease. Hence, at least for children with high-risk disease, it may be prudent to consider ATRA-chemotherapy based treatment to prevent such higher proportion of differentiation syndrome and related morbidities. Furthermore, the daily administration of ATO needs stringent cardiac and electrolyte monitoring, which remains often challenging in resource-challenged settings. Hence, the appropriate risk-stratification and treatment adaptations needs to be prospectively studied among children, especially in low-middle income countries.
APML is notoriously well known to have significantly high proportion of early death even prior to initiation of definitive therapy in the community. This is driven mainly by bleeding manifestations, especially intracranial bleeds. In this study conducted in low-middle income country (LMIC) setting, the observed early mortality rate was 5.5% with the overall mortality rate of 10%. In contrast, the early mortality rate of APML observed in national cancer databases even in resource-rich countries like United States is 7.2%, and other studies conducted in LMICs reporting estimates exceeding 30%. Hence, this study does not capture the true mortality or burden of this disease from a community or epidemiological perspective, and likely underestimates the early mortality of childhood APML in India. The data recorded in cancer registries also does not capture incidence and mortality of this uncommon yet important disease as a separate category [4]. Collaborative research groups like Indian Pediatric Oncology Group (InPOG) working on multi-centre studies on childhood cancer should lead studies to capture treatment patterns and survival outcomes of childhood APML across the country [5]
Radiologists' rating for comparative qualitative assessment of intravoxel incoherent motion using novel analysis methods
No full textObjective
The objective was to assess qualitative interpretability and quantitative precision and reproducibility of intravoxel incoherent motion (IVIM) parametric images evaluated using novel IVIM analysis methods for diagnostic accuracy.
Methods
Intravoxel incoherent motion datasets of 55 patients (male/female = 41:14; age = 17.8 ± 5.5 years) with histopathology-proven osteosarcoma were analyzed. Intravoxel incoherent motion parameters—diffusion coefficient (D), perfusion fraction (f), and perfusion coefficient (D∗)—were estimated using 5 IVIM analysis methods—(i) biexponential (BE) model, (ii) BE-segmented fitting 2-parameter (BESeg-2), (iii) BE-segmented fitting 1-parameter (BESeg-1), (iv) BE model with total variation penalty function (BE + TV), and (v) BE model with Huber penalty function (BE + HPF). Qualitative scoring in a 5-point Likert scale (uninterpretable: 1; poor: 2; fair: 3; good: 4; excellent: 5) was performed by 2 radiologists for 4 criteria: (a) tumor shape and margin, (b) morphologic correlation, (c) noise suppression, and (d) overall interpretability. Interobserver agreement was evaluated using Spearman rank-order correlation (rs). Precision and reproducibility were evaluated using within-subject coefficient of variation (wCV) and between-subject coefficient of variation (bCV).
Results
BE + TV and BE + HPF produced significantly (P < 10−3) higher qualitative scores for D (fair–good [3.3–3.8]) than BE (poor [2.3]) and for D* (poor–fair [2.2–2.7]) and f (fair–good [3.2–3.8]) than BE, BESeg-2, and BESeg-1 (D∗: uninterpretable–poor [1.3–1.9] and f: poor–fair [1.5–3]). Interobserver agreement for qualitative scoring was rs = 0.48–0.59, P < 0.009. BE + TV and BE + HPF showed significantly (P < 0.05) improved reproducibility in estimating D (wCV: 24%–31%, bCV: 21%–31% improvement) than the BE method and D* (wCV: 4%–19%, bCV: 5%–19% improvement) and f (wCV: 25%–49%, bCV: 25%–47% improvement) than BE, BESeg-2, and BESeg-1 methods.
Conclusions
BE + TV and BE + HPF demonstrated qualitatively and quantitatively improved IVIM parameter estimation and may be considered for clinical use further
Tweaking photo CO<sub>2</sub> reduction by altering Lewis acidic sites in metalated‐porous organic polymer for adjustable H<sub>2</sub>/CO ratio in syngas production
No full textHerein, we have specifically designed two metalated porous organic polymers (Zn-POP and Co-POP) for syngas (CO+H2) production from gaseous CO2. The variable H2/CO ratio of syngas with the highest efficiency was produced in water medium (without an organic hole scavenger and photosensitizer) by utilizing the basic principle of Lewis acid/base chemistry. Also, we observed the formation of entirely different major products during photocatalytic CO2 reduction and water splitting with the help of the two catalysts, where CO (145.65 μmol g−1 h−1) and H2 (434.7 μmol g−1 h−1) production were preferentially obtained over Co-POP & Zn-POP, respectively. The higher electron density/better Lewis basic nature of Co-POP was investigated further using XPS, XANES, and NH3-TPD studies, which considerably improve CO2 activation capacity. Moreover, the structure–activity relationship was confirmed via in situ DRIFTS and DFT studies, which demonstrated the formation of COOH* intermediate along with the thermodynamic feasibility of CO2 reduction over Co-POP while water splitting occurred preferentially over Zn-POP
Metal deficiency tailored by the 18-electron rule stabilizes metal-based inorganic compounds
No full textThe 18-electron (18-e-) rule is typically restricted to predicting the stability of transition-metal-based complexes. Herein, we report the use of the 18-e- to predict the stability in a family of intermetallics MNiSn (M = V, Cr, Fe, and Co) crystallizing in the Co1.75Ge structure type. Site deficiencies at the M site obtained from single-crystal X-ray diffraction are understood as attaining a stable noble gas electronic configuration. The density functional theory -based structure calculation confirms that the deficient structure is more stable than the ideal occupation available at the crystal lattice. MnNiSn, which crystallizes in the half-Heusler crystal structure, depicts the role of covalent radii of the constituent elements in determining the crystal structure. Using X-ray absorption spectroscopy and X-ray photoelectron spectroscopy, the local structure of the above-mentioned compounds was also elucidated, supporting the role of deficiency tuned valence fluctuation to attain a 18-e- configuration that eventually leads to the formation of stable compounds
Virtual Reality in Preoperative Planning of Complex Cranial Surgery
No full textObjective
Changing paradigms of neurosurgical training and limited operative exposure during the residency period have made it necessary to evaluate newer technologies for training. Virtual reality (VR) technology provides three-dimensional reconstruction of routine imaging, along with the ability to see as well as interact. The application of VR technology in operative planning, which is an important part of neurosurgical training, has been incompletely studied so far.
Methods
Sixteen final-year residents, post-M.Ch. (magister chirurgiae) residents, and fellows were included as study participants. They were divided into 2 groups based on their seniority for further analysis. Five complex cranial cases were selected and a multiple-choice question-based test was prepared by the authors, with 5 questions for each of the cases. The pretest score was determined based on performance on the test after participants accessed routine preoperative imaging. The posttest score was calculated after use of the VR system (ImmersiveTouch VR System, ImmersiveTouch Inc.). Analysis was performed by the investigators, who were blinded to the identity of the participant. Subanalysis based on the type of case and type of question was performed. Feedback was obtained from each participant regarding VR use.
Results
There was an overall improvement in scores from pretest to posttest, which was also noted in the analysis based on the participants’ seniority. This improvement was noted to be more for the vascular cases (15.89%) compared with the tumor cases (7.84%). Participants also fared better in questions related to surgical anatomy and surgical approach, compared with questions based on the diagnosis. There was overall positive feedback from participants regarding VR use, and most participants wanted VR to become a routine part of operative planning.
Conclusions
Our study shows that there is improvement in understanding of surgical aspects after use of this VR system
Protumorigenic role of the atypical cadherin FAT1 by the suppression of PDCD10 via RelA/miR221‐3p/222‐3p axis in glioblastoma
No full textThe atypical cadherin FAT1 function either as a pro or antitumorigenic in tumors of different tissue origins. Our group previously demonstrated the protumorigenic nature of FAT1 signaling in glioblastoma (GBM). In this study, we investigated how FAT1 influences the expression of clustered oncomiRs (miR-221-3p/miR-222-3p) and their downstream effects in GBM. Through several experiments involving the measurement of specific gene/microRNA expression, gene knockdowns, protein and cellular assays, we have demonstrated a novel oncogenic signaling pathway mediated by FAT1 in glioma. These results have been verified using antimiRs and miR-mimic assays. Initially, in glioma-derived cell lines (U87MG and LN229), we observed FAT1 as a novel up-regulator of the transcription factor NFκB-RelA. RelA then promotes the expression of the clustered-oncomiRs, miR-221-3p/miR-222-3p, which in turn suppresses the expression of the tumor suppressor gene (TSG), PDCD10 (Programmed cell death protein10). The suppression of PDCD10, and other known TSG targets (PTEN/PUMA), by miR-221-3p/miR-222-3p, leads to increased clonogenicity, migration, and invasion of glioma cells. Consistent with our in-vitro findings, we observed a positive expression correlation of FAT1 and miR-221-3p, and an inverse correlation of FAT1 and the miR-targets (PDCD10/PTEN/PUMA), in GBM tissue-samples. These findings were also supported by publicly available GBM databases (The Cancer Genome Atlas [TCGA] and The Repository of Molecular Brain Neoplasia Data [Rembrandt]). Patients with tumors displaying high levels of FAT1 and miR-221-3p expression (50% and 65% respectively) experienced shorter overall survival. Similar results were observed in the TCGA-GBM database. Thus, our findings show a novel FAT1/RelA/miR-221/miR-222 oncogenic-effector pathway that downregulates the TSG, PDCD10, in GBM, which could be targeted therapeutically in a specific manner
MatNLI: An open-source MATLAB-based solver for the non-linear inversion in elastography
No full textElastography has emerged as one of the most promising non-invasive clinical tools. In elastography, a stiffness map or elastogram is generated by solving an inverse problem of elasticity utilizing the tissue motion data acquired using magnetic resonance imaging or ultrasound. Among various inverse algorithms devoted to elastography, non-linear inversion coupled with the finite element method has demonstrated excellent applicability in extracting complex physics of the tissue. The development and implementation of such an inverse algorithm are challenging and often unavailable to clinicians. In the present work, we offer an open-source parallel MATLAB implementation of an efficient non-linear inversion algorithm based on the finite element method for different isotropic material models, viz., linear elastic and viscoelastic materials in the regime of compressible and nearly incompressible materials. Additionally, the framework has been extended to account for anisotropy by assuming transversely isotropic material. For the optimization module, the gradient of the objective function to the model parameters has been computed using the Adjoint method. Different case studies involving smooth variations and piece-wise discontinuities in the material property distribution are explored, and the efficacy of the inversion algorithm in reconstructing the stiffness map is discussed. In addition, noise is added to the synthetic data to depict a realistic setup, i.e., to prevent inverse crimes, and enhance the numerical stability and robustness of the current implementation. The present framework with general-purpose computer implementation could be beneficial for academic and clinical uses and may aid researchers in strengthening their existing frameworks and developing new algorithmic ideas
Defects tune the strong metal–support interactions in copper supported on defected titanium dioxide catalysts for CO<sub>2</sub> reduction
No full textA highly active and stable Cu-based catalyst for CO2 to CO conversion was demonstrated by creating a strong metal–support interaction (SMSI) between Cu active sites and the TiO2-coated dendritic fibrous nano-silica (DFNS/TiO2) support. The DFNS/TiO2–Cu10 catalyst showed excellent catalytic performance with a CO productivity of 5350 mmol g–1 h–1 (i.e., 53,506 mmol gCu–1 h–1), surpassing that of almost all copper-based thermal catalysts, with 99.8% selectivity toward CO. Even after 200 h of reaction, the catalyst remained active. Moderate initial agglomeration and high dispersion of nanoparticles (NPs) due to SMSI made the catalysts stable. Electron energy loss spectroscopy confirmed the strong interactions between copper NPs and the TiO2 surface, supported by in situ diffuse reflectance infrared Fourier transform spectroscopy and X-ray photoelectron spectroscopy. The H2-temperature programmed reduction (TPR) study showed α, β, and γ H2-TPR signals, further confirming the presence of SMSI between Cu and TiO2. In situ Raman and UV–vis diffuse reflectance spectroscopy studies provided insights into the role of oxygen vacancies and Ti3+ centers, which were produced by hydrogen, then consumed by CO2, and then again regenerated by hydrogen. These continuous defect generation–regeneration processes during the progress of the reaction allowed long-term high catalytic activity and stability. The in situ studies and oxygen storage complete capacity indicated the key role of oxygen vacancies during catalysis. The in situ time-resolved Fourier transform infrared study provided an understanding of the formation of various reaction intermediates and their conversion to products with reaction time. Based on these observations, we have proposed a CO2 reduction mechanism, which follows a redox pathway assisted by hydrogen
Insights into the CO<sub>2</sub> capture characteristics within the hierarchical pores of carbon nanospheres using small-angle neutron scattering
No full textUnderstanding adsorption processes at the molecular level has transformed the discovery of engineered materials for maximizing gas storage capacity and kinetics in adsorption-based carbon capture applications. In this work, we studied the molecular mechanism of gas (CO2, H2, methane, and ethane) adsorption inside an interconnected porous network of carbon. This was achieved by synthesizing novel macro–meso–microporous carbon (M3C) nanospheres with interconnected pore structures. The M3Cs showed a CO2 capture capacity of 5.3 mmol/g at atmospheric CO2 pressure, with excellent kinetics. This was due to fast CO2 adsorption within the interconnected hierarchical macro–meso–microporous M3C. In situ small-angle neutron scattering (SANS) under various CO2 pressures indicated that the macro- and mesopores of M3C enable fast diffusion of CO2 molecules inside the micropores, where adsorbed CO2 molecules densify into a liquid-like state. This strong densification of CO2 molecules causes fast CO2 diffusion in the macro- and mesopores of M3C, restarting the adsorption cycle for fresh CO2 molecules until all pores are completely filled. Notably, M3C also showed good capture capacities for hydrogen and various hydrocarbons, with excellent selectivity toward ethane over methane
Increasing risk of simultaneous occurrence of flash drought in major global croplands
No full textSimultaneous occurrence of flash drought in major croplands can pose challenges for global food security. However, drivers of flash drought co-occurrence in the observed and future climate remain unrecognized. Using observations and climate model simulations, we examine the simultaneous occurrence of flash droughts in 16 major global croplands that grow wheat, rice, and maize. We show that significant warming combined with decreasing precipitation led to an increased frequency of flash droughts in several major croplands during the observed climate (1981–2020). The simultaneous occurrence of flash drought in many croplands in the same year has significantly (p-value = 0.007) increased during 1981–2020 and is likely to continue. Nine out of 16 major global croplands are projected to witness an increased frequency of flash droughts under the warming climate. The observed and projected rise in flash droughts in global croplands is mainly driven by vapor pressure deficit. The positive phase of El Nino Southern Oscillation influences flash drought co-occurrence in 10 out of 16 major cropland regions and remains a dominating factor of flash droughts co-occurrence in the future. Enhanced climate warming and increased frequency of El Nino events can further enhance the occurrence of simultaneous flash droughts in several major croplands, with substantial implications for food productio