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Resistance or intolerance to the available tyrosine kinase inhibitors (TKIs) remains a treatment challenge for patients with chronic myeloid leukaemia. We aimed to report the safety, antileukaemic activity, and pharmacokinetics of oral vodobatinib, a novel selective BCR::ABL1TKI, in patients with Philadelphia chromosome-positive (Ph-positive) chronic myeloid leukaemia who previously received at least three TKIs, including ponatinib and asciminib.

IMPORTANCE: Stereotactic body radiation therapy (SBRT) for spinal metastases improves symptomatic outcomes and local control compared to conventional radiotherapy. Treatment failure most often occurs within the epidural space, where dose is constrained by the risk of radiation myelitis (RM). Current constraints designed to prevent RM after spine SBRT are derived from limited data. OBJECTIVE: To characterize the risk of RM after spine SBRT and to update the dosimetric constraints for preventing it. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted in a single tertiary cancer care center with patients treated for spinal metastases from 2014 to 2023. All included participants had undergone spine SBRT, had a minimum of 1-month follow-up with magnetic resonance imaging (MRI), a maximal cord dose to a voxel (Dmax) greater than 0 Gy, and no overlapping prior radiotherapy. In all, 2051 patients received SBRT to 2835 spinal metastases (levels C1-L2) during the study period. EXPOSURES: Three-fraction spine SBRT to a prescription dose of 27 to 36 Gy. MAIN OUTCOMES AND MEASURES: RM defined as radiographic evidence of spinal cord injury in the treatment field, classified as grade (G) 1 to G4 or G3 to G4 per the Common Terminology Criteria for Adverse Events, version 5.0. Multiple dosimetric parameters of the true spinal cord structure were assessed for an association with risk of RM to determine the important covariates associated with this toxicity. RESULTS: The analysis included 1423 patients (mean [SD] age, 61.6 [12.9] years; 695 [48.8%] females and 728 [51.1%] males) who received SBRT for 1904 spinal metastases. Among them, 30 cases of RM were identified, 19 of which were classified as G3 to G4. Two years after SBRT, the rate of G1 to G4 RM was 1.8% (95% CI, 1.2%-2.5%) and the rate of G3 to G4 RM was 1.1% (95% CI, 0.7%-1.7%). The minimum dose to the 0.1 cm3 of spinal cord receiving the greatest dose (D0.1cc) was the most important covariate on univariable cause-specific hazards regression for RM (for G3 to G4: hazard ratio, 2.14; 95% CI, 1.68-2.72; P < .001). A true cord D0.1cc of 19.1 Gy and Dmax of 20.8 Gy estimated a 1.0% risk (95% CI, 0.3%-1.6% and 0.4%-1.6%, respectively) of G3 to G4 RM 2 years after SBRT. CONCLUSIONS AND RELEVANCE: The findings of this cohort study indicate that a cord (myelogram or MRI-derived) D0.1cc constraint of 19.1 Gy and a Dmax constraint of 20.8 Gy correspond with a 1.0% risk of G3 to G4 RM at 2 years.

In India, currently, there are no standard guidelines for the management of moderate acute malnutrition (MAM). Previous research in Bangladesh has shown that children with MAM have impaired gut microbiota development, and microbiota-directed complementary foods (MDCF) can potentially repair their gut microbiota.

The carbon dioxide (CO2) methanation reaction plays a crucial role in Power-to-Gas (PtG) technology, enabling efficient energy storage and CO2mitigation. The development of highly active, selective, and cost-effective catalysts is critical for improving the efficiency of this process. Here, we explore the role of Mn in Ni-Mn/Al2O3and Ni3Fe-Mn/Al2O3catalysts for the CO2methanation reaction. We synthesize, characterize and test the catalysts for the CO2methanation reaction. Co-impregnation is chosen for synthesis since smaller crystallite sizes are made, and higher activity is achieved. Furthermore, Mn does not integrate into the metallic Ni particles, instead, MnO is formed. Similarly, reduction of Ni3Fe-Mn/Al2O3catalyst results in the formation of MnO along with the Ni3Fe alloy particles. The presence of Mn-oxides also appears to hinder the interaction of NiO with Al2O3, leading to better reducibility. Despite this, Ni3Fe-Mn/Al2O3exhibits a lower percent reduction than Ni-Mn/Al2O3due to the presence of less reducible Fe-oxides. For a 15 wt% Ni loading, the catalyst containing Ni/Mn molar ratio = 3 displays superior catalytic performance due to larger metallic Ni surface area, which results from a combination of better reducibility and smaller particle size. The site time conversion of this optimum catalyst is higher than that of several previously reported Ni-Mn catalysts. The beneficial effects of Mn on Ni/Al2O3do not extend to Ni3Fe/Al2O3, since the increase in alloy surface area is relatively smaller. Furthermore, the Ni particles are more stable than Ni3Fe alloy particles for CO2methanation, irrespective of the presence or absence of Mn.

The most frequent type of breast cancer in women is infiltrating ductal carcinoma, followed by infiltrating lobular carcinoma and triple‐negative breast cancer, which account for 10%–15% of cases. Since this disease is not aggressive in its early stages and thus does not flee with the breast duct with this perspective, Epidermal Growth Factor Receptor (EGFR) was chosen with its relevance in stage 0 breast cancer as a primary target. The study aimed to evaluate the protective effects of 19 flavonoids against breast cancer. In addition, pharmacokinetics investigations, molecular docking, free energy calculations, and molecular dynamics simulations were used to evaluate the molecular interactions, stability, and draggability between the phytoconstituents and the EGFR. The acquired results showed that myricetin, which has been compared to raloxifene, is the top docked score compound from the list of flavonoids; the docking score is −9.26 kcal/mol, and standard raloxifene showed −5.39 kcal/mol against epidermal growth factor receptor. The ADME profile shows the drug‐like properties. MD simulations revealed that the myricetin complex is more stable than the raloxifene complex, and pharmacophore modeling studies validated the hydrogen bonding interactions. The PASS online program predicted the biological spectrum of flavonoids against the breast cancer‐causing enzyme. Key parameters like RMSD, RMSF, RoG, hydrogen bonds, PCA, DCCM, and FEL analysis indicated better stability for myricetin. These results suggest that myricetin is a promising drug candidate against breast cancer.