Characterizing the voxel-based approaches in radioembolization dosimetry with reDoseMC.

BACKGROUND: Yttrium-90 ( 90 Y $^{90}{\rm {Y}}$ ) represents the primary radioisotope used in radioembolization procedures, while holmium-166 ( 166 Ho $^{166}{\rm {Ho}}$ ) is hypothesized to serve as a viable substitute for 90 Y $^{90}{\rm {Y}}$ due to its comparable therapeutic potential and improved quantitative imaging. Voxel-based dosimetry for these radioisotopes relies on activity images obtained through PET or SPECT and dosimetry methods, including the voxel S-value (VSV) and the local deposition method (LDM). However, the evaluation of the accuracy of absorbed dose calculations has been limited by the use of non-ideal reference standards and investigations restricted to the liver. The objective of this study was to expand upon these dosimetry characterizations by investigating the impact of image resolutions, voxel sizes, target volumes, and tissue materials on the accuracy of 90 Y $^{90}{\rm {Y}}$ and 166 Ho $^{166}{\rm {Ho}}$ dosimetry techniques. METHODS: A specialized radiopharmaceutical dosimetry software called reDoseMC was developed using the Geant4 Monte Carlo toolkit and validated by benchmarking the generated 90 Y $^{90}{\rm {Y}}$ kernels with published data. The decay spectra of both 90 Y $^{90}{\rm {Y}}$ and 166 Ho $^{166}{\rm {Ho}}$ were also compared. Multiple VSV kernels were generated for the liver, lungs, soft tissue, and bone for isotropic voxel sizes of 1 mm, 2 mm, and 4 mm. Three theoretical phantom setups were created with 20 or 40 mm activity and mass density inserts for the same three voxel sizes. To replicate the limited spatial resolutions present in PET and SPECT images, image resolutions were modeled using a 3D Gaussian kernel with a Full Width at Half Maximum (FWHM) ranging from 0 to 16 mm and with no added noise. The VSV and LDM dosimetry methods were evaluated by characterizing their respective kernels and analyzing their absorbed dose estimates calculated on theoretical phantoms. The ground truth for these estimations was calculated using reDoseMC. RESULTS: The decay spectra obtained through reDoseMC showed less than a 1% difference when compared to previously published experimental data for energies below 1.9 MeV in the case of 90 Y $^{90}{\rm {Y}}$ and less than 1% for energies below 1.5 MeV for 166 Ho $^{166}{\rm {Ho}}$ . Additionally, the validation kernels for 90 Y $^{90}{\rm {Y}}$ VSV exhibited results similar to those found in published Monte Carlo codes, with source dose depositions having less than a 3% error margin. Resolution thresholds ( FWHM thresh s ${\rm {FWHM}}_\mathrm{thresh}{\rm {s}}$ ), defined as resolutions that resulted in similar dose estimates between the LDM and VSV methods, were observed for 90 Y $^{90}{\rm {Y}}$ . They were 1.5 mm for bone, 2.5 mm for soft tissue and liver, and 8.5 mm for lungs. For 166 Ho $^{166}{\rm {Ho}}$ , the accuracy of absorbed dose deposition was found to be dependent on the contributions of absorbed dose from photons. Volume errors due to variations in voxel size impacted the final dose estimates. Larger target volumes yielded more accurate mean doses than smaller volumes. For both radioisotopes, the radial dose profiles for the VSV and LDM approximated but never matched the reference standard. CONCLUSIONS: reDoseMC was developed and validated for radiopharmaceutical dosimetry. The accuracy of voxel-based dosimetry was found to vary widely with changes in image resolutions, voxel sizes, chosen target volumes, and tissue material; hence, the standardization of dosimetry protocols was found to be of great importance for comparable dosimetry analysis.

Clinical significance of the advanced lung cancer inflammation index in patients with limited-stage small cell lung cancer treated with chemoradiotherapy.

The aim of the study was to investigate the prognostic significance of the advanced lung cancer inflammation index (ALI) in patients with limited-stage small-cell lung cancer (LS-SCLC) undergoing definite chemo-radiotherapy (CRT). We included 87 patients with LS-SCLC from South Korea, treated between 2005 and 2019 with definite CRT. ALI was calculated using body mass index, serum albumin, and neutrophil-lymphocyte ratio. We categorized 38 patients into the high ALI group (ALI ≥ 44.3) and 48 into the low ALI group (ALI < 44.3). Patients in the high ALI group exhibited longer overall survival (OS) than patients in the low ALI group. In multivariate analysis, prophylactic cranial irradiation (hazard ratio [HR] = 0.366, 95% confidence interval [CI] 0.20-0.66, P = 0.0008), and high ALI (HR = 0.475, 95% CI 0.27-0.84, P = 0.0103) were identified as independent prognostic factors for predicting better OS. Notably, a high ALI score was particularly indicative of longer survival in patients treated with the combination of etoposide and cisplatin. In conclusion, this study demonstrated that a high pretreatment ALI was significantly associated with better OS in patients with LS-SCLC undergoing definite CRT. This suggests that ALI could be a useful tool for predicting prognosis and guiding chemotherapy regimen selections in clinical practice for LS-SCLC.

Distinct CT imaging features of new liver metastases from primary genitourinary cancers.

PURPOSE: To apply natural language processing (NLP) to a large volume of structured radiology reports in the investigation of CT imaging features of new liver metastases from primary genitourinary cancers. METHODS: In this retrospective study, a previously reported NLP model was applied to consecutive structured CT reports from 2016 to 2022 to predict those patients with primary genitourinary cancer who developed liver metastasis. Pathology or imaging follow-up served as the reference standard for validating NLP predictions. Subsequently, diagnostic CTs of the identified patients were qualitatively assessed by two radiologists, whereby several imaging features of new liver metastasis were assessed. Proportions of the assessed imaging features were compared between primary genitourinary cancers using the Chi-square or Fisher's exact test. RESULTS: In 112 patients (mean age = 72 years; 83 males), the majority of new liver metastases were hypovascular (73.2%), well defined (76.6%), homogenous (66.9%), and without necrotic/cystic component (73.2%). There was a higher proportion of iso- to hyperdense liver metastases for primary kidney cancer vs other primary genitourinary cancers (42.5% in kidney cancer; 2.3% in ureter/bladder cancer, 8% in prostate cancer, and 0% in testicular cancer; p < 0.05) and a higher proportion of new liver metastases with ill-defined margin for primary prostate cancer vs other primary genitourinary cancers (44.0% in prostate cancer, 15.0% in kidney cancer, 18.6% in ureter/bladder cancer, and 25.0% in testicular cancer; p < 0.05). CONCLUSION: New liver metastases from primary genitourinary cancers tend to be hypovascular and show several distinct imaging features between different primary genitourinary cancers.

Association of baseline factors with 1-year outcomes in the SB11-ranibizumab equivalence trial: A post hoc analysis.

PURPOSE: To identify baseline factors associated with 1-year outcomes when treating neovascular age-related macular degeneration (nAMD) with ranibizumab biosimilar SB11 or reference ranibizumab (rRBZ), and to compare efficacy of the two products within subgroups judged to be clinically relevant. DESIGN: Post hoc analysis of a prospective, equivalence phase 3 randomized clinical trial (RCT) METHODS: 705 patients with nAMD were randomized 1:1 to receive SB11 or rRBZ for 48 weeks. Pooled and randomized groups were used to identify baseline factors associated with clinical outcomes at Week 52 using multiple linear regression models. Significant factors identified in regression analyses were confirmed in analyses of variance. Subgroup analyses comparing best-corrected visual acuity (BCVA) changes between SB11 and rRBZ were conducted. RESULTS: 634 (89.9%) participants completed the 52-week visit. Regression analyses showed that younger age, lower BCVA, and smaller total lesion area at baseline were associated with greater BCVA gain at Week 52, while older age, lower BCVA, and thicker central subfield thickness (CST) at baseline were predictors of greater CST reduction in the pooled group. Subgroup analyses demonstrated that BCVA outcomes appeared comparable for the SB11 and rRBZ groups. CONCLUSION: Post hoc analyses of the SB11-rRBZ equivalence study showed that baseline age, BCVA, CST, and total lesion area were prognostic factors for visual or anatomical outcomes of nAMD, while subgroup analyses demonstrated comparable results for SB11 and rRBZ. Collectively, the results appear comparable to similar RCTs of anti-vascular endothelial growth factor reference products for nAMD and strengthen confidence in the biosimilarity of SB11.

Validation of the 2022 European LeukemiaNet risk stratification for acute myeloid leukemia.

This study aimed to validate the 2022 European LeukemiaNet (ELN) risk stratification for acute myeloid leukemia (AML). A total of 624 newly diagnosed AML patients from 1998 to 2014 were included in the analysis. Genetic profiling was conducted using targeted deep sequencing of 45 genes based on recurrent driver mutations. In total, 134 (21.5%) patients had their risk classification reassessed according to the 2022 ELN risk stratification. Among those initially classified as having a favorable risk in 2017 (n = 218), 31 and 3 patients were reclassified as having intermediate risk or adverse risk, respectively. Among the three subgroups, the 2022 ELN favorable-risk group showed significantly longer survival outcomes than the other groups. Within the 2017 ELN intermediate-risk group (n = 298), 21 and 46 patients were reclassified as having favorable risk or adverse risk, respectively, and each group showed significant stratifications in survival outcomes. Some patients initially classified as having adverse risk in 2017 were reclassified into the intermediate-risk group (33 of 108 patients), but no prognostic improvements were observed in this group. A multivariable analysis identified the 2022 ELN risk stratification, age, and receiving allogeneic hematopoietic cell transplantation as significant prognostic factors for survival. The 2022 ELN risk stratification enables more precise decisions for proceeding with allogeneic hematopoietic cell transplantation for AML patients.

Corrigendum: A single-institution experience with 177Lu RPT workflow improvements and qualifying the SPECT/CT imaging for dosimetry.

[This corrects the article DOI: 10.3389/fonc.2024.1331266.].

Association of Lateral Pelvic Lymph Nodes with Disease Recurrence and Organ Preservation in Patients with Distal Rectal Adenocarcinoma Treated with Total Neoadjuvant Therapy.

OBJECTIVE: Assess the significance of enlarged lateral lymph nodes (LLN) for disease recurrence, metastasis, and organ preservation in patients with rectal cancer. BACKGROUND: Optimal treatment of rectal adenocarcinoma involving LLN is subject to debate. METHODS: A post hoc analysis of the OPRA trial, a multicenter study of patients with rectal cancer treated with total neoadjuvant therapy (TNT) followed by total mesorectal excision or watch-and-wait management. We analyzed the association of visible LLN (LLN+), LLN≥7 mm (short axis) on baseline MRI, and LLN≥4 mm on restaging MRI with recurrence, metastasis, and rectum preservation. RESULTS: At baseline, 57 out of 324 (18%) patients had LLN+. In 30 (53%) of 57 patients with LLN+ on baseline MRI, the LLN disappeared after TNT. Disease recurrence in LLN was rare (3.5% of patients with LLN+ and 0.4% of patients with LLN-). All patients with recurrence in LLN also had distant metastasis. The rate of organ preservation was significantly lower in patients with LLN≥4 mm on restaging MRI (P=0.013). We found no significant differences in rates of local recurrence or metastasis between patients with LLN+ vs. LLN- and in patients with LLN≥7 vs.<7 mm on baseline MRI. LLN dissection was performed in 3 patients; 2 of them died of distant metastasis. CONCLUSIONS: LLN involvement is not associated with disease recurrence or metastasis, but persistence of LLN≥4 mm after TNT is negatively associated with rectum preservation in patients with locally advanced rectal cancer treated with TNT. Dissection of lateral nodes likely benefits few patients.

Increased Risk of Incident Chronic Obstructive Pulmonary Disease and Related Hospitalizations in Tuberculosis Survivors: A Population-Based Matched Cohort Study.

BACKGROUND: Tuberculosis (TB) survivors have an increased risk of developing chronic obstructive pulmonary disease (COPD). This study assessed the risk of COPD development and COPD-related hospitalization in TB survivors compared to controls. METHODS: We conducted a population-based cohort study of TB survivors and 1:1 age- and sex-matched controls using data from the Korean National Health Insurance Service database collected from 2010 to 2017. We compared the risk of COPD development and COPD-related hospitalization between TB survivors and controls. RESULTS: Of the subjects, 9.6% developed COPD, and 2.8% experienced COPD-related hospitalization. TB survivors had significantly higher COPD incidence rates (36.7/1,000 vs. 18.8/1,000 person-years, P < 0.001) and COPD-related hospitalization (10.7/1,000 vs. 4.3/1,000 person-years, P < 0.001) than controls. Multivariable Cox regression analyses revealed higher risks of COPD development (adjusted hazard ratio [aHR], 1.63; 95% confidence interval [CI], 1.54-1.73) and COPD-related hospitalization (aHR, 2.03; 95% CI, 1.81-2.27) in TB survivors. Among those who developed COPD, the hospitalization rate was higher in individuals with post-TB COPD compared to those with non-TB COPD (10.7/1,000 vs. 4.9/1,000 person-years, P < 0.001), showing an increased risk of COPD-related hospitalization (aHR, 1.84; 95% CI, 1.17-2.92). CONCLUSION: TB survivors had higher risks of incident COPD and COPD-related hospitalization compared to controls. These results suggest that previous TB is an important COPD etiology associated with COPD-related hospitalization.

Enhanced Postsurgical Cancer Treatment Using Methacrylated Glycol Chitosan Hydrogel for Sustained DNA/Doxorubicin Delivery and Immunotherapy.

Background: Cancer recurrence and metastasis are major contributors to treatment failure following tumor resection surgery. We developed a novel implantable drug delivery system utilizing glycol chitosan to address these issues. Glycol chitosan is a natural adjuvant, inducing dendritic cell activation to promote T helper 1 cell immune responses, macrophage activation, and cytokine production. Effective antigen production by dendritic cells initiates T-cell-mediated immune responses, aiding tumor growth control. Methods: In this study, we fabricated multifunctional methacrylated glycol chitosan (MGC) hydrogels with extended release of DNA/doxorubicin (DOX) complex for cancer immunotherapy. We constructed the resection model of breast cancer to verify the anticancer effects of MGC hydrogel with DNA/DOX complex. Results: This study demonstrated the potential of MGC hydrogel with extended release of DNA/DOX complex for local and efficient cancer therapy. The MGC hydrogel was implanted directly into the surgical site after tumor resection, activating tumor-related immune cells both locally and over a prolonged period of time through immune-reactive molecules. Conclusions: The MGC hydrogel effectively suppressed tumor recurrence and metastasis while enhancing immunotherapeutic efficacy and minimizing side effects. This biomaterial-based drug delivery system, combined with cancer immunotherapy, can substantial improve treatment outcomes and patient prognosis.

A single-institution experience with 177Lu RPT workflow improvements and qualifying the SPECT/CT imaging for dosimetry.

Background and purpose: Implementing any radiopharmaceutical therapy (RPT) program requires a comprehensive review of system readiness, appropriate workflows, and training to ensure safe and efficient treatment delivery. A quantitative assessment of the dose delivered to targets and organs at risk (OAR) using RPT is possible by correlating the absorbed doses with the delivered radioactivity. Integrating dosimetry into an established RPT program demands a thorough analysis of the necessary components and system fine-tuning. This study aims to report an optimized workflow for molecular radiation therapy using 177Lu with a primary focus on integrating patient-specific dosimetry into an established radiopharmaceutical program in a radiation oncology setting. Materials and methods: We comprehensively reviewed using the Plan-Do-Check-Act (PDCA) cycle, including efficacy and accuracy of delivery and all aspects of radiation safety of the RPT program. The GE Discovery SPECT/CT 670DR™ system was calibrated per MIM protocol for dose calculation on MIM SurePlan™ MRT software. Jaszcak Phantom with 15-20 mCi of 177Lu DOTATATE with 2.5 µM EDTA solution was used, with the main energy window defined as 208 keV ±10% (187.6 to 229.2 keV); the upper scatter energy window was set to 240 keV ±5% (228 to 252 keV), while the lower scatter energy window was 177.8 keV ±5% (168.9 to 186.7 keV). Volumetric quality control tests and adjustments were performed to ensure the correct alignment of the table, NM, and CT gantry on SPECT/CT. A comprehensive end-to-end (E2E) test was performed to ensure workflow, functionality, and quantitative dose accuracy. Results: Workflow improvements and checklists are presented after systematically analyzing over 400 administrations of 177Lu-based RPT. Injected activity to each sphere in the NEMA Phantom scan was quantified, and the MIM Sureplan MRT reconstruction images calculated activities within ±12% of the injected activity. Image alignment tests on the SPECT/CT showed a discrepancy of more than the maximum tolerance of 2.2 mm on any individual axis. As a result of servicing the machine and updating the VQC and COR corrections, the hybrid imaging system was adjusted to achieve an accuracy of <1 mm in all directions. Conclusion: Workflows and checklists, after analysis of system readiness and adequate training for staff and patients, are presented. Hardware and software components for patient-specific dosimetry are presented with a focus on hybrid image registration and correcting any errors that affect dosimetric quantification calculation. Moreover, this manuscript briefly overviews the necessary quality assurance requirements for converting diagnostic images into dosimetry measurement tools and integrating dosimetry for RPT based on 177Lu.

MRI imaging features for predicting macrotrabecular-massive subtype hepatocellular carcinoma: a systematic review and meta-analysis.

PURPOSE: To identify significant MRI features associated with macrotrabecular-massive hepatocellular carcinoma (MTM-HCC), and to assess the distribution of Liver Imaging Radiology and Data System (LI-RADS, LR) category assignments. METHODS: PubMed and EMBASE were searched up to March 28, 2023. Random-effects model was constructed to calculate pooled diagnostic odds ratios (DORs) and 95% confidence intervals (CIs) for each MRI feature for differentiating MTM-HCC from NMTM-HCC. The pooled proportions of LI-RADS category assignments in MTM-HCC and NMTM-HCC were compared using z-test. RESULTS: Ten studies included 1978 patients with 2031 HCCs (426 (20.9%) MTM-HCC and 1605 (79.1%) NMTM-HCC). Six MRI features showed significant association with MTM-HCC: tumor in vein (TIV) (DOR = 2.4 [95% CI, 1.6-3.5]), rim arterial phase hyperenhancement (DOR =2.6 [95% CI, 1.4-5.0]), corona enhancement (DOR = 2.6 [95% CI, 1.4-4.5]), intratumoral arteries (DOR = 2.6 [95% CI, 1.1-6.3]), peritumoral hypointensity on hepatobiliary phase (DOR = 2.2 [95% CI, 1.5-3.3]), and necrosis (DOR = 4.2 [95% CI, 2.0-8.5]). The pooled proportions of LI-RADS categories in MTM-HCC were LR-3, 0% [95% CI, 0-2%]; LR-4, 11% [95% CI, 6-16%]; LR-5, 63% [95% CI, 55-71%]; LR-M, 12% [95% CI, 6-19%]; and LR-TIV, 13% [95% CI, 6-22%]. In NMTM-HCC, the pooled proportions of LI-RADS categories were LR-3, 1% [95% CI, 0-2%]; LR-4, 8% [95% CI, 3-15%]; LR-5, 77% [95% CI, 71-82%]; LR-M, 5% [95% CI, 3-7%]; and LR-TIV, 6% [95% CI, 2-11%]. MTM-HCC had significantly lower proportion of LR-5 and higher proportion of LR-M and LR-TIV categories. CONCLUSIONS: Six MRI features showed significant association with MTM-HCC. Additionally, compared to NMTM-HCC, MTM-HCC are more likely to be categorized LR-M and LR-TIV and less likely to be categorized LR-5. CLINICAL RELEVANCE STATEMENT: Several MR imaging features can suggest macrotrabecular-massive hepatocellular carcinoma subtype, which can assist in guiding treatment plans and identifying potential candidates for clinical trials of new treatment strategies. KEY POINTS: • Macrotrabecular-massive hepatocellular carcinoma is a subtype of HCC characterized by its aggressive nature and unfavorable prognosis. • Tumor in vein, rim arterial phase hyperenhancement, corona enhancement, intratumoral arteries, peritumoral hypointensity on hepatobiliary phase, and necrosis on MRI are indicative of macrotrabecular-massive hepatocellular carcinoma. • Various MRI characteristics can be utilized for the diagnosis of the macrotrabecular-massive hepatocellular carcinoma subtype. This can prove beneficial in guiding treatment decisions and identifying potential candidates for clinical trials involving novel treatment approaches.

Synergistic Effect of Electrical and Biochemical Stimulation on Human iPSC-Derived Neural Differentiation in a Microfluidic Electrode Array Chip.

Neural differentiation is crucial for advancing our understanding of the nervous system and developing treatments for neurological disorders. The advanced methods and the ability to manipulate the alignment, proliferation, and differentiation of stem cells are essential for studying neuronal development and synaptic interactions. However, the utilization of human induced pluripotent stem cells (iPSCs) for disease modeling of neurodegenerative conditions may be constrained by the prolonged duration and uncontrolled cell differentiation required for functional neural cell differentiation. Here, we developed a microfluidic chip to enhance the differentiation and maturation of specific neural lineages by placing aligned microelectrodes on the glass surface to regulate the neural differentiation of human iPSCs. The utilization of electrical stimulation (ES) in conjunction with neurotrophic factors (NF) significantly enhanced the efficiency in generating functional neurons from human iPSCs. We also observed that the simultaneous application of NF and ES to human iPSCs promoted their differentiation and maturation into functional neurons while increasing synaptic interactions. Our research demonstrated the effect of combining NF and ES on human iPSC-derived neural differentiation.

Long-Term Impacts of COVID-19 on Severe Exacerbation and Mortality in Adult Asthma: A Nationwide Population-Based Cohort Study.

BACKGROUND: In adults with asthma, the long-term impact of previous coronavirus disease 2019 (COVID-19) on severe exacerbations and mortality is unclear. OBJECTIVE: We evaluated the long-term risk of severe exacerbation and mortality in adults with asthma who recovered from COVID-19. METHODS: Using the Korean National Health Insurance claim-based database, we compared the risk of severe exacerbations (emergency room visits or hospitalization) and mortality in adults with asthma aged greater than 20 years who had recovered from COVID-19 between October 8, 2020, and December 16, 2021 (COVID-19 cohort, n = 10,739) with 1:1 propensity score-matched controls (n = 10,739). RESULTS: During a median follow-up of 87 days (range, 15-448 days), the incidence rate of severe exacerbations in the COVID-19 cohort and the matched cohort was 187.3 and 119.3 per 10,000 person-years, respectively. The COVID-19 cohort had a higher risk of severe exacerbation compared with the matched cohort (hazard ratio = 1.57; 95% CI, 1.06-2.32). During a median follow-up of 360 days (range, 15-721 days), the incidence rate of death in the COVID-19 and matched cohorts was 128.3 and 73.5 per 10,000 person-years, respectively. The COVID-19 cohort had a higher risk of death (hazard ratio = 1.76; 95% CI, 1.33-2.30) compared with the matched cohort. When further analyzed by COVID-19 severity, severe COVID-19 was associated with a 5.12-fold (95% CI, 3.27-8.01) and 7.31-fold (95% CI, 5.41-9.88) increased risk of severe exacerbation and death, respectively, but non-severe COVID-19 was not. CONCLUSIONS: Our study shows that severe COVID-19 is associated with an increased long-term risk of severe exacerbation and mortality among individuals with asthma.

Mutations in myeloid transcription factors and activated signaling genes predict chronic myeloid leukemia outcomes.

ABSTRACT: Advancements in genomics are transforming the clinical management of chronic myeloid leukemia (CML) toward precision medicine. The impact of somatic mutations on treatment outcomes is still under debate. We studied the association of somatic mutations in epigenetic modifier genes and activated signaling/myeloid transcription factors (AS/MTFs) with disease progression and treatment failure in patients with CML after tyrosine kinase inhibitor (TKI) therapy. A total of 394 CML samples were sequenced, including 254 samples collected at initial diagnosis and 140 samples taken during follow-up. Single-molecule molecular inversion probe (smMIP)-based next-generation sequencing (NGS) was conducted targeting recurrently mutated loci in 40 genes, with a limit of detection of 0.2%. Seventy mutations were detected in 57 diagnostic samples (22.4%), whereas 64 mutations were detected in 39 of the follow-up samples (27.9%). Carrying any mutation at initial diagnosis was associated with worse outcomes after TKI therapy, particularly in AS/MTF genes. Patients having these mutations at initial diagnosis and treated with imatinib showed higher risks of treatment failure (hazard ratio, 2.53; 95% confidence interval, 1.13-5.66; P = .0239). The adverse prognostic impact of the mutations was not clear for patients treated with second-generation TKIs. The multivariate analysis affirmed that mutations in AS/MTF genes independently serve as adverse prognostic factors for molecular response, failure-free survival, and progression risk. Additionally, there was an observable nonsignificant trend indicating a heightened risk of progression to advanced disease and worse overall survival. In conclusion, mutations in the AS/MTF genes using smMIP-based NGS can help identify patients with a potential risk of both treatment failure and progression and may help upfront TKI selection.

Nanoengineered Polymeric RNA Nanoparticles for Controlled Biodistribution and Efficient Targeted Cancer Therapy.

RNA nanotechnology, including rolling circle transcription (RCT), has gained increasing interest as a fascinating siRNA delivery nanoplatform for biostable and tumor-targetable RNA-based therapies. However, due to the lack of fine-tuning technologies for RNA nanostructures, the relationship between physicochemical properties and siRNA efficacy of polymeric siRNA nanoparticles (PRNs) with different sizes has not yet been fully elucidated. Herein, we scrutinized the effects of size/surface chemistry-tuned PRNs on the biological and physiological interactions with tumors. PRNs with adjusted size and surface properties were prepared using sequential engineering processes: RCT, condensation, and nanolayer deposition of functional biopolymers. Through the RCT process, nanoparticles of three sizes with a diameter of 50-200 nm were fabricated and terminated with three types of biopolymers: poly-l-lysine (PLL), poly-l-glutamate (PLG), and hyaluronic acid (HA) for different surface properties. Among the PRNs, HA-layered nanoparticles with a diameter of ∼200 nm exhibited the most effective systemic delivery, resulting in superior anticancer effects in an orthotopic breast tumor model due to the CD44 receptor targeting and optimized nanosized structure. Depending on the type of PRNs, the in vivo siRNA delivery with protein expression inhibition differed by up to approximately 20-fold. These findings indicate that the types of layered biopolymers and the PRNs size mediate efficient polymeric siRNA delivery to the targeted tumors, resulting in high RNAi-induced therapeutic efficacy. This RNA-nanotechnology-based size/surface editing can overcome the limitations of siRNA therapeutics and represents a potent built-in module method to design RNA therapeutics tailored for targeted cancer therapy.

Prognostic analysis according to European LeukemiaNet 2022 risk stratification for elderly patients with acute myeloid leukemia treated with decitabine.

OBJECTIVES: This study aimed to evaluate the prognostic significance of the revised European LeukemiaNet (ELN)-2022 risk stratification model for 123 elderly acute myeloid leukemia (AML) patients treated with decitabine chemotherapy. RESULTS: Based on the ELN-2022 risk stratification, 15 (12.2%), 51 (41.5%), and 57 (46.3%) patients were classified as having favorable, intermediate, and high-risk AML, respectively. In comparison with the ELN-2017 risk stratification, the ELN-2022 risk stratification re-assigned 26 (21.1%) and three (2.4%) patients to the adverse and favorable risk groups, respectively. Survival analysis revealed distinctive overall survival (OS) outcomes among the ELN-2022 risk groups (6-month OS rate: 73.3%, 52.9%, and 47.7% for favorable, intermediate, and adverse risk, respectively; P = 0.101), with a parallel trend observed in the event-free survival (EFS) (6-month EFS rate: 73.3%, 52.9%, and 45.6% for favorable, intermediate, and adverse risk, respectively; P = 0.049). Notably, both OS and EFS in the favorable risk group were significantly superior in comparison to that of the adverse risk group (OS: P = 0.040, EFS: P = 0.030). Although the ELN-2022 C-index (0.559) was greater than the ELN-2017 C-index (0.539), the result was not statistically significant (P = 0.059). Based on the event net reclassification index, we consistently observed significant improvements in the ELN-2022 risk stratification for overall survival (0.21 at 6 months). CONCLUSION: In conclusion, the revised ELN-2022 risk stratification model may have improved the risk classification of elderly AML patients treated with hypomethylating agents compared to the ELN-2017 risk stratification model.

Impacts of regular physical activity on hospitalisation in chronic obstructive pulmonary disease: a nationwide population-based study.

INTRODUCTION: Studies that comprehensively evaluate the association between physical activity (PA) levels, particularly by quantifying PA intensity, and healthcare use requiring emergency department (ED) visit or hospitalisation in patients with chronic obstructive pulmonary disease (COPD) are limited in Korea. METHODS: The risk of all-cause and respiratory ED visit or hospitalisation according to the presence or absence of COPD and the level of PA was evaluated in a retrospective nationwide cohort comprising 3308 subjects with COPD (COPD cohort) and 293 358 subjects without COPD (non-COPD cohort) from 2009 to 2017. RESULTS: The COPD group exhibited a higher relative risk of all-cause and respiratory ED visit or hospitalisation across all levels of PA compared with the highly active control group (≥1500 metabolic equivalents (METs)-min/week). Specifically, the highest risk was observed in the sedentary group (adjusted HR (aHR) (95% CI) = 1.70 (1.59 to 1.81) for all-cause ED visit or hospitalisation, 5.45 (4.86 to 6.12) for respiratory ED visit or hospitalisation). A 500 MET-min/week increase in PA was associated with reductions in all-cause and respiratory ED visit or hospitalisation in the COPD cohort (aHR (95% CI) = 0.92 (0.88 to 0.96) for all-cause, 0.87 (0.82 to 0.93) for respiratory cause). CONCLUSIONS: Compared with the presumed healthiest cohort, the control group with PA>1500 METs-min/week, the COPD group with reduced PA has a higher risk of ED visit or hospitalisation.

Crystallographic and Photophysical Analysis on Facet-Controlled Defect-Free Blue-Emitting Quantum Dots.

The burgeoning demand for commercializing self-luminescing quantum dot (QD) light-emitting diodes (LEDs) has stimulated extensive research into environmentally friendly and efficient QD materials. Hydrofluoric acid (HF) additive improves photoluminescence (PL) properties of blue-emitting ZnSeTe QDs, ultimately reaching a remarkable quantum yield (QY) of 97% with an ultranarrow peak width of 14 nm after sufficient HF addition. The improvement in optical properties of the QDs is accompanied by a morphology change of the particles, forming cubic-shaped defect-free ZnSeTe QDs characterized by a zinc blende (ZB) crystal structure. This treatment improves the QD-emitting properties by facilitating facet-specific growth, selectively exposing stabilized (100) facets, and reducing the lattice disorders. The facet-specific growth process gives rise to defect-free monodispersed cubic dots that exhibit remarkably narrow and homogeneous PL spectra. Meticulous time-resolved spectroscopic studies allow an understanding of the correlation between ZnSeTe QDs' particle shape and performance following HF addition. These investigations shed light on the intricacies of the growth mechanism and the factors influencing the PL efficiency of the resulting QDs. The findings significantly contribute to understanding the role of HF treatment in tailoring the optical properties of ZnSeTe QDs, thereby bringing it closer to the realization of highly efficient and bright QD-LEDs for various practical applications.

Recent Advances in Electrochemical Detection of Cell Energy Metabolism.

Cell energy metabolism is a complex and multifaceted process by which some of the most important nutrients, particularly glucose and other sugars, are transformed into energy. This complexity is a result of dynamic interactions between multiple components, including ions, metabolic intermediates, and products that arise from biochemical reactions, such as glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), the two main metabolic pathways that provide adenosine triphosphate (ATP), the main source of chemical energy driving various physiological activities. Impaired cell energy metabolism and perturbations or dysfunctions in associated metabolites are frequently implicated in numerous diseases, such as diabetes, cancer, and neurodegenerative and cardiovascular disorders. As a result, altered metabolites hold value as potential disease biomarkers. Electrochemical biosensors are attractive devices for the early diagnosis of many diseases and disorders based on biomarkers due to their advantages of efficiency, simplicity, low cost, high sensitivity, and high selectivity in the detection of anomalies in cellular energy metabolism, including key metabolites involved in glycolysis and mitochondrial processes, such as glucose, lactate, nicotinamide adenine dinucleotide (NADH), reactive oxygen species (ROS), glutamate, and ATP, both in vivo and in vitro. This paper offers a detailed examination of electrochemical biosensors for the detection of glycolytic and mitochondrial metabolites, along with their many applications in cell chips and wearable sensors.