Mapi Research Trust

BackgroundEarly identification of septic patients who will require vasopressor support could provide a critical window for hemodynamic optimisation, yet current bedside cues often appear only when shock is imminent.ObjectiveWe aimed to develop and validate an interpretable electronic health record (EHR)–based machine-learning model that predicts vasopressor initiation several hours before therapy in intensive care unit (ICU) patients with sepsis.MethodsWe conducted a retrospective study using the MIMIC-IV v2.2 database (2008–2019). We screened adult Sepsis-3 ICU stays and labeled the patients who commenced continuous vasopressor infusions 6 to 48 hours after admission as cases; we defined controls as sepsis patients with ICU stays ≥48 hours and no vasopressor exposure. We performed one to one nearest neighbour matching on age, sex, Charlson index, SOFA score with the cardiovascular component removed, weight, and early lactate/hematocrit availability to minimise confounding. We engineered demographic, physiological, and laboratory features measured from −6 to −2 hours relative to vasopressor initiation (or a matched time point) under multiple parameter combinations. We trained seven algorithms with Monte Carlo cross validation and evaluated performance on an independent validation set. We assessed model interpretability with Shapley values.ResultsWe analyzed 1,539 cases and 1,431 controls; the independent validation set comprised 751 stays (~25%). A Random Forest classifier achieved an area under the receiver operating characteristic (AUROC) of 0.75 (95% CI, 0.72–0.79), a sensitivity of 0.74 (95% CI, 0.69–0.78), a specificity of 0.65 (95% CI, 0.60–0.70), a precision of 0.70 (95% CI, 0.66–0.74) and a F1 score of 0.72 (95% CI, 0.68–0.75) at the Youden’s index threshold. The model outperformed simple surrogates—mean blood pressure (AUROC, 0.68; 95% CI, 0.64–0.72) and modified shock index (AUROC, 0.65; 95% CI, 0.62–0.69)—and a reproduced bidirectional LSTM (AUROC, 0.73; 95% CI, 0.70–0.77). Key predictors included declining mean blood pressure at − 2 to −4 hours, elevated lactate ( > 2.5 mmol/L), and hematocrit outside 30–37%. Model alerts would occur two to four hours before vasopressor initiation, providing actionable lead time for clinicians.ConclusionsThis proof-of-concept study shows that routinely collected ICU data can predict impending vasopressor initiation with clinically interpretable outputs. However, these findings reflect internal validation only and should be interpreted with caution. External validation on multi-center retrospective cohorts, followed by silent-mode prospective evaluation, is warranted to confirm generalisability and to assess the real-world impact on time-to-vasopressor, fluid balance, and patient outcomes.Supplementary informationThe online version contains supplementary material available at 10.1186/s12911-025-03274-3.

In the ICARUS project, European partners collaborate to develop and scale innovative technologies for recovering and refining secondary raw materials from silicon photovoltaic (PV) manufacturing. The production of photovoltaic modules generates significant quantities of waste, particularly silicon kerf, graphite, and silica residues from ingot and wafer manufacturing. ICARUS aims to transform these waste streams into high‐value secondary materials suitable for reintegration into the PV value chain and other industrial applications. Four industrial pilot‐scale processes are developed, targeting the purification and reuse of these materials. Results from the pilots demonstrate both the technical feasibility and economic potential of substituting these recovered materials for virgin and critical raw materials. This work provides a viable pathway toward a more resource‐efficient and circular PV manufacturing industry.

ABSTRACT This study aimed to evaluate specific psychometric properties of a latent-factor conceptualisation of mental well-being using the Short Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS) in Singapore. We also examined measurement invariance and concurrent validity. A secondary self-report cross-sectional dataset (n = 3,043) was used. Results of confirmatory factor analysis indicated the SWEMWBS’s high internal consistency and unidimensional factor structure. Full invariance (i.e. configural, metric, and scalar) was observed across all demographic groups (i.e. gender, education, religiosity, and employment status), except race and marital status. Overall, as hypothesised, Singaporeans with higher SWEMWBS scores reported greater present and future life satisfaction and subjective health, and lower psychological distress. Altogether, the findings suggest that the SWEMWBS is a reliable, valid, and practical measurement tool which can be used to study mental well-being and evaluate programmes and interventions which seek to track and improve mental well-being in Singapore, where mental health is a national priority.

PurposeTumor imaging or therapy using cancer specific carriers combined with a radioisotope has huge potential. In radiopharmaceutical development, it is important to ensure target specificity and minimal binding to normal tissues for both tumor detection and treatment. In previous studies, we identified CAPRIN-1 as a cancer-specific antigen, which is widely expressed on the cell surface membrane in many types of solid cancers, and created TRK-950, a humanized monoclonal antibody raised against CAPRIN-1, followed by conducting clinical development. In this proof-of-concept study, we prepared radiolabeled form of TRK-950 and investigated their potential as tumor imaging or therapeutic agents.MethodsAn [111In]In-DOTA-TRK-950 was prepared and administered to tumor-bearing mice, and its tumor accumulation and pharmacokinetics were evaluated with SPECT/CT imaging. Next, the anti-tumor effect of a [177Lu]Lu-DOTA-TRK-950 was evaluated. Additionally, radiolabeled TRK-950-F(ab’)2, an antibody fragment of TRK-950, was similarly evaluated for their potential.ResultsAt 72 h after administration of [111In]In-DOTA-TRK-950, tumor accumulation was high at 24.8% IA/g for 4T1 and 18.9% IA/g for HT-29, both of which are CAPRIN-1-high cancer cells, while tumor accumulation remained low at 7.5% IA/g for MNNG/HOS, which are CAPRIN-1-low cancer cells. Regarding therapeutic evaluations, strong anti-tumor effects and prolonged survival were observed after administration of [177Lu]Lu-DOTA-TRK-950 to 4T1 and HT-29 tumor-bearing mice. Furthermore, these results were also observed in the 4T1 tumor-bearing model with radiolabeled TRK-950-F(ab’)2, which has shorter pharmacokinetics.ConclusionThis study demonstrates that radiopharmaceuticals targeting CAPRIN-1, including radiolabeled TRK-950 and TRK-950-F(ab’)2, have high potential as radiopharmaceuticals.

393 Background: Metastatic pancreatic cancer (mPC) and its treatments significantly impact patients’ (pts) health-related quality of life (HRQoL). POLO, a randomized, double-blind, placebo-controlled phase 3 trial evaluated the efficacy of olaparib as maintenance therapy in mPC pts who had not progressed during ≥16 weeks of first-line platinum-based chemo. HRQoL was assessed in POLO using EORTC QLQ-C30. To enhance the interpretation of HRQoL scores in POLO, we derived EORTC QLQ-C30 reference (ref) values for mPC from the literature, as these had not been previously established. Methods: A systematic literature review was conducted to identify existing baseline values in published data. EORTC QLQ-C30 ref values were calculated by deriving mean scores based on studies meeting all inclusion criteria. EORTC QLQ-C30 mean values were calculated for POLO using pooled baseline data from both study arms (olaparib; placebo). Results: Out of 186 studies identified, 4 met all inclusion criteria. Depending on respective EORTC QLQ-C30 subscale, the final sample sizes ranged from n=466 to n=639. Compared to the newly derived EORTC QLQ-C30 ref values based on the literature, POLO pts reported markedly better HRQoL scores at baseline across most subscales, with eight subscales showing differences of >15 points (table). Conclusions: This is the first study to systematically derive EORTC QLQ-C30 ref values for mPC. We found that mPC pts enrolled in POLO had better HRQoL scores compared with those reported in the literature and often close to or better than general population norm data, possibly due to positive effects of prior platinum-based first-line treatment, resolution of chemotherapy-related symptoms, response shift, or a combination. These newly derived ref values enhance the interpretation of patients’ HRQoL trajectory within a maintenance treatment setting. [Table: see text]

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