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Structural and physicochemical stability of 3D-printed bolus materials used in radiotherapy
Abstract In radiotherapy, boluses ensure dose buildup at the skin and adapt to complex anatomy, requiring stable, well-conforming materials. This study aimed to investigate the effect of ionising radiation (70 Gy, 6 MV) on changes in the physicochemical properties of two materials used for 3D printing bolus materials for radiotherapy: acrylonitrile butadiene styrene ABS and thermoplastic copolyester TPC. Surface roughness, tribological parameters, hardness, dimensional stability, Fourier transform infrared spectra FTIR, and differential scanning calorimetry DSC data were assessed. After irradiation, small statistically significant changes in roughness parameters were observed for both materials, with ABS exhibiting greater surface degradation. In tribological tests, ABS demonstrated a 70% reduction in coefficient of friction, while TPC remained stable. FTIR spectra revealed changes characteristic of ABS degradation and oxidation (decreases in the intensity of butadiene bands, CH₂ shifts, and increases in carbonyl bands). Subtle chemical stability and potential cross-linking were observed in TPC. DSC suggests no changes in TPC and a decrease in the glass transition temperature of ABS, suggesting slight structural degradation. A slight increase in hardness was observed in ABS and TPC after irradiation, with only minimal dimensional changes in ABS. Based on the data obtained, X-ray radiation affected the tested materials differently. Although both retain their function after exposure to therapeutic doses, TPC exhibits greater chemical and mechanical resistance. Combined with its greater flexibility, this may result in improved clinical adhesion and reproducibility during radiotherapy. Further studies will include analysis of adhesion and dose distribution (Part 2).
The post-BCMA playbook: RD118 GPRC5D CAR T cells for myeloma
A lattice oxygen-free design for efficient and stable photothermal methane dry reforming
Author Correction: Forced oscillation technique in progressive pulmonary fibrosis in a single-center retrospective study
Insights from single-cell omics: cellular heterogeneity as a foundation of clinical outcome in chronic myeloid leukemia
Abstract The BCR::ABL1 tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML) represent a paradigm for molecularly targeted therapy. However, clinical outcomes (rate/depth of response, treatment-free remission [TFR], progression to blast crisis [BC]) and adverse events vary among patients. While additional somatic mutations have been invoked to explain varying clinical outcomes, we here propose a complementary perspective based on single-cell omics (sc-omics) approaches that have enabled unprecedented resolution of the cellular ecosystems, including their composition, interactions, and activity. In patients who were treatment-naïve and in chronic phase (CP), this has revealed differences in the growth-rate of BCR::ABL1+ clones, ratio of TKI-insensitive leukemic stem cells (LSC) to residual hematopoietic stem cells (HSC), and immune cell composition, factors that collectively contribute to variability in therapy efficacy. Together these findings suggest that cellular heterogeneity serves as a foundation of clinical outcome in CML. Patients who remain in CP exhibit an erythroid signature in LSC, while those progressing to BC manifest an inflammatory profile, additional mutations, and expansion of early progenitors. Deep responders with active natural killer, and regulatory T cells are more likely to sustain TFR. Similarly, the outcomes of donor lymphocyte infusion after allogeneic stem cell transplant are heterogeneous, and reflect differences in preexisting T-cell clonotypes, their expansion, and interaction with leukemic cells in responders vs nonresponders. Here, we summarize key insights from sc-omics in CML, and propose an actionable road map to further leverage these technologies. This includes mechanistically explaining heterogeneity, predicting therapy response and BC, tracking leukemogenic clones longitudinally, targeting TKI-insensitive LSC, and restoring hematopoiesis from residual HSCs.
Treatments for idiopathic pulmonary fibrosis are on the horizon
Geographic spillover of antimicrobial resistance from mass distribution of azithromycin
Abstract Large-scale, placebo-controlled, cluster-randomized trials in high-mortality settings in sub-Saharan Africa demonstrated a 14–18% reduction in childhood mortality following twice-annual mass drug administration (MDA) of azithromycin among children aged 1–59 months. Azithromycin MDA also selected for antimicrobial resistance (AMR), particularly macrolide resistance. It is unknown whether the AMR from azithromycin MDA could spill over to neighboring untreated populations. If present, such geographic spillover effects could lead trials to underestimate AMR risks. We assess between-village geographic spillover effects of genotypic macrolide resistance using metagenomic deep sequencing in rectal swabs collected from 300 children in 30 monitoring villages in Niger after two years of MDA in 594 surrounding villages. Conditional permutation tests assess associations between proximal azithromycin treatment intensity and resistance gene abundance. We find no evidence of geographic spillover of macrolide resistance in untreated villages, as the genetic load of AMR remains at baseline levels in placebo-treated villages regardless of surrounding azithromycin treatment intensity (Spearman ρ = −0.05, P = 0.83). Sensitivity analyses confirm robustness across metrics, and no spillover effects are detected for other antibiotic classes. Azithromycin MDA-induced macrolide resistance appears localized to treated villages, mitigating some concerns about geographic spillover of AMR to nearby untreated villages at 24 months.
Clinical features and inflammatory signatures of patients with persistent gastrointestinal long COVID two years after severe SARS-CoV-2 infection
Abstract Persistent gastrointestinal (GI) symptoms are increasingly recognized as part of long COVID, yet their underlying mechanisms remain poorly defined. We conducted an exploratory case-series study of 80 adults hospitalized with severe COVID-19 in March-May 2020 in Manaus, Brazil. Two years post-infection, participants underwent structured clinical interviews and longitudinal cytokine analysis (IL-1β, IL-6, IL-8, IL-10, IL-12, and TNF-α). Overall, 30 participants reported ongoing GI symptoms (GI group) predominantly gastroesophageal reflux (63%), abdominal pain (43%), and diarrhea (37%). Compared with participants without GI symptoms (nGI group, n = 50), the GI group reported a higher burden of additional long COVID symptoms, including palpitations, headache, and arthralgia. They also exhibited distinct clinical and laboratory features, including lower baseline creatinine and ferritin levels and altered platelet indices. Although IL-6 levels were lower during the acute hospitalization phase, they became significantly elevated at four months post-infection (D120, p = 0.005), suggesting delayed inflammatory response. Ascendent biomarker analysis identified TNF-α as highly expressed in a large proportion of GI group. The findings suggest GI problems can persist two years after severe COVID-19, and long-term inflammatory dysregulation may underlie the pathogenesis of these GI manifestations in long COVID. Prolonged gastrointestinal surveillance in COVID-19 survivors is necessary.
The fully human anti-GPRC5D CAR T-cell therapy RD118 induces durable remissions in relapsed/refractory multiple myeloma
Abstract GPRC5D has emerged as a promising therapeutic target in relapsed/refractory multiple myeloma (R/R MM), particularly following progression after B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T-cell (CAR-T) therapies. RD118 is a novel CAR-T therapy incorporating a fully human single-domain antibody fragment targeting GPRC5D. In this phase 1 study, 18 R/R patients (17 with MM and 1 with a history of primary plasma cell leukemia) received a single infusion of RD118 at 1.0 × 106, 2.0 × 106, or 3.0 × 106 CAR+ T cells per kg. At a median follow-up of 17.0 months, the overall response rate (ORR) was 94.4%, including 72.2% complete or stringent complete responses. Among the 7 patients previously exposed to BCMA-directed CAR-T therapy, ORR reached 85.7%. Median progression-free survival (PFS) was 18.2 months (95% confidence interval, 14.4 to not estimable), with 12-month PFS and overall survival rates of 82.1% and 93.3%, respectively. Cytokine release syndrome occurred in 88.9% of the patients, primarily grade 1 to 2. One patient developed grade 3 immune effector cell–associated neurotoxicity, which resolved within 72 hours. No cerebellar toxicities or treatment-related deaths were reported. These findings support that RD118 is a highly effective and safe therapeutic option for heavily pretreated R/R MM. This trial was registered at www.clinicaltrials.gov as #NCT05759793 and #NCT05219721.
How ‘forest bathing’ keeps lungs healthy
Photothermal effects control ultrafast charge transport in titanium carbide MXenes
Abstract Titanium carbide MXene (Ti₃C₂T ₓ ) is an emerging metallic material with promise for (opto)electronics and thermal management. Yet how photoexcitation—particularly via photogenerated thermal energy—modifies its charge carrier dynamics remains poorly understood. By combining time-resolved terahertz spectroscopy and transient reflectance measurements, we reveal a long-lived, photo-induced suppression of conductivity, which we attribute to efficient lattice heating and slow heat dissipation in Ti₃C₂T x . A systematic variation of pump photon energy reveals that this ‘negative’ photoconductivity can equivalently be induced by lattice temperature increases, indicating a thermal origin. Repetition-rate-dependent transient reflectance measurements further show residual heat persisting over 100 ns, substantially longer than in conventional metals. Our work presents a unified understanding of photothermal effects in Ti₃C₂T ₓ and their influence on non-equilibrium charge transport, underscoring its potential for photothermal electronics and light-to-thermal energy storage applications.
Reliability-based assessment of road design features and crash risk using a socio-economic index for safety prioritization
Abstract This study investigates the relationship between road design features and crash risk on a 186 km segment of Highway No. 36 in Iran. A socio-economic risk index was developed by integrating Empirical Bayes crash predictions, severity-based social crash costs, and construction cost estimates. This index was incorporated into a reliability framework, where limit-state functions and Monte Carlo simulation were used to compute the exceedance probability of crash risk. Geometric data were collected through field surveys, and traffic and crash data were obtained from the Khorasan Razavi Road Maintenance and transportation organization’s database (2019–2023). The results show that horizontal curves have the highest crash risk, while segments longer than 4 km exhibit the lowest values. Crash risk also increases with wider lanes, gravel shoulders, greater shoulder widths, and embankment slopes steeper than 4%. Grades between 0 and 3% reduce risk, whereas steeper grades elevate it. Guardrails demonstrate mixed effects, reducing risk at lower levels but not consistently at higher ones. The reliability-based probabilistic framework integrates crash data, societal costs with severity, and construction costs to systematically prioritize safety interventions, offering a clear methodological advantage over deterministic approaches.
Targeting proteostasis addiction in AML
Funding cuts could put research into emerging threats to lung health at risk
Machine-learning-guided tungsten single atoms promote oxyhydroxides for noble-metal-free water electrolysis
Green zinc oxide nanoparticles improve zinc bioavailability and mitigate high temperature stress in rice
The proteostasis network is a therapeutic target in acute myeloid leukemia
Abstract Oncogenic growth places great strain and dependence on protein homeostasis (proteostasis). This has made proteostasis pathways attractive therapeutic targets in cancer, but efforts to drug these pathways have yielded disappointing clinical outcomes. One exception is proteasome inhibitors, which are approved for the frontline treatment of multiple myeloma. However, proteasome inhibitors are largely ineffective for the treatment of other cancers at tolerable doses, including acute myeloid leukemia (AML), although reasons for these differences are unknown. Here, we determined that proteasome inhibitors are ineffective in AML due to their inability to disrupt proteostasis. In response to proteasome inhibition, AML cells activated HSF1 and increased autophagic flux to preserve proteostasis. Genetic inactivation of HSF1 sensitized AML cells to proteasome inhibition, marked by accumulation of unfolded protein, activation of the protein kinase R (PKR)–like endoplasmic reticulum kinase (PERK)–mediated integrated stress response, severe reductions in protein synthesis, proliferation and cell survival, and significant slowing of disease progression and extension of survival in vivo. Similarly, combined autophagy and proteasome inhibition suppressed proliferation, synergistically killed human AML cells, and significantly reduced AML burden and extended survival in vivo. Furthermore, autophagy and proteasome inhibition preferentially suppressed protein synthesis and colony formation and induced apoptosis in cells from patients with primary AML, including AML stem/progenitor cells, compared with normal hematopoietic stem/progenitor cells. Combined autophagy and proteasome inhibition activated a terminal integrated stress response, which was surprisingly PKR. These studies unravel how proteostasis pathways are coopted to promote AML growth, progression and drug resistance and reveal that disabling the proteostasis network is a promising strategy to therapeutically target AML.