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MOSUNETUZUMAB DEMONSTRATES DURABLE RESPONSES IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA AND >=2 PRIOR THERAPIES: UPDATED ANALYSIS OF A PIVOTAL PHASE II STUDY B Introduction: b Mosunetuzumab (Mosun) is a CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells. B Conclusion: b Fixed-duration Mosun monotherapy demonstrated a high CR rate at EOT in pts with I R i / I R i FL, with many pts remaining event-free 2 years after EOT. [Extracted from the article]

Reasons for cessation included progressive disease 52%; bridging to other therapy 10%; death 6%; toxicity 4%. 8 pts received up to 2 subsequent lines of therapy, with 2 receiving CAR-T therapy. B Introduction: b RRDLBCL outcomes remain poor despite autologous transplant and CAR-T therapies offering potential cure to a minority. POLATUZUMAB, BENDAMUSTINE & RITUXIMAB EFFICACY IN RELAPSED/REFRACTORY TRIAL-INELIGIBLE LARGE B CELL LYMPHOMA PATIENTS: AN AUSTRALIAN LYMPHOMA REGISTRY (LARDR) STUDY. [Extracted from the article]

Abstract: Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) ineligible for available salvage therapies have limited options for long-term disease control, necessitating novel treatments. Previously, magrolimab (anti-cluster-of-differentiation-47 antibody) plus rituximab (M+R) demonstrated ability to induce complete responses (CR) in R/R DLBCL. Here, we report 3-year follow-up data from this phase 1b/2 study assessing long-term safety and efficacy of M+R, and initial safety and efficacy of M+R plus gemcitabine-oxaliplatin (M+R-GemOx), in R/R DLBCL. After magrolimab priming, 4 groups of patients received M+R, 10 to 45 mg/kg magrolimab with 375 mg/m2 rituximab; patients receiving M+R-GemOx received 30 or 45 mg/kg magrolimab with 375 mg/m2 rituximab, 1000 mg/m2 gemcitabine, and 100 mg/m2 oxaliplatin. Primary end points were treatment-emergent adverse events (TEAEs) and objective response rate (ORR). Secondary end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Of 132 patients treated, 99 received M+R and 33 received M+R-GemOx. Most common any-grade TEAEs were fatigue (M+R, 40%; M+R-GemOx, 70%), infusion-related reactions (M+R, 39%), or anemia (M+R-GemOx, 70%). Treatment-related TEAEs led to magrolimab discontinuation in 7% (M+R) and 6% (M+R-GemOx). One death was considered treatment related (M+R-GemOx, colitis). M+R ORR was 24% (CR, 12%), and median DOR was 9.3 months. Median PFS and OS were 1.8 and 9.2 months, respectively. M+R-GemOx ORR was 52% (CR, 39%); 12-month DOR rate was 66.6% (95% confidence interval, 33.1-86.1). Median PFS and OS were 3.9 months and not reached, respectively. These results demonstrate that M+R with/without GemOx is well tolerated, and M+R-GemOx has clinical activity in patients with R/R DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT02953509., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)

Mantle cell lymphoma (MCL) is a clinically heterogeneous B-cell neoplasm with unique clinicopathological features, accounting for 5% of all non-Hodgkin lymphoma. Although for many chemoimmunotherapy can lead to durable remissions, those with poor baseline prognostic factors, namely blastoid morphology, TP53 aberrancy and Ki67 >30%, will have less durable responses to conventional therapies. With this in mind, clinical trials have focused on novel targeted therapies to improve outcomes. This review details the recent advances in the understanding of MCL biology and outlines the recommended diagnostic strategies and evidence-based approaches to treatment., (© 2024 Royal Australasian College of Physicians.)

Central nervous system germ cell tumors (CNS-GCT) are malignant neoplasms that arise predominantly during adolescence and young adulthood. These tumors are typically sensitive to treatment, but resulting long-term health deficits are common. Additional clinical challenges include surgical risks associated with tumor biopsy, and need to determine treatment response for adapting radiotherapy protocols. The aim of this study was to establish the detectability of circulating-tumor DNA (ctDNA) from cerebrospinal fluid (CSF) of children with CNS-GCT as a potential biomarker. We obtained CSF from patients with CNS-GCT by lumbar puncture or intra-operatively. Cell-free DNA (cfDNA) was extracted and subjected to low-pass whole genome sequencing (LP-WGS). Copy-number alterations (CNAs) were inferred and served as a marker of measurable residual disease (MRD). Comparisons with imaging findings and tumor marker levels were made. A total of 29 CSF samples from 21 patients (16 with germinoma, 5 with non-germinomatous GCT) were sequenced. Twenty samples from 19 patients were collected at diagnosis, and 9 samples from 7 patients were collected during or after therapy. Among the diagnostic samples, CNAs were detected in samples from 17/19 patients (89%), which included 8 with marker-negative tumors. Specific clinical scenarios suggested that serial cfDNA analysis may carry utility in tracking treatment responses as well as clarifying indeterminate imaging findings. Our results provide evidence for the high-sensitivity in detecting ctDNA from CSF of CNS-GCT patients using LP-WGS, with potential utility for non-invasive diagnosis and disease monitoring in upcoming CNS-GCT studies., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Hospital for Sick Children Research Ethical Board (REB # 1000071241) and the Hong Kong Children’s Hospital Research Ethics Committee (HKCH-REC-2020-068). Written informed consent was obtained from all patients, their parents or guardians. Consent for publication: Written informed consent for the publication was obtained from all patients participants, their parents or guardians. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Glofitamab monotherapy induces durable remission in patients with relapsed or refractory diffuse large B-cell lymphoma after two or more previous therapies, but has not previously been assessed as a second-line therapy. We investigated the efficacy and safety of glofitamab plus gemcitabine-oxaliplatin (Glofit-GemOx) versus rituximab (R)-GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma., Methods: The phase 3, randomised, open-label STARGLO trial was done at 62 centres in 13 countries in Asia and Australia, Europe, and North America. We recruited transplant-ineligible patients (aged ≥18 years) with histologically confirmed relapsed or refractory diffuse large B-cell lymphoma after one or more previous therapies. Patients were randomly assigned in permuted blocks (block size of six) via an interactive voice or web response system (2:1; stratified by 1 vs ≥2 previous lines of therapy and relapsed vs refractory status) to Glofit-GemOx (intravenous gemcitabine 1000 mg/m 2 and oxaliplatin 100 mg/m 2 plus glofitamab step-up dosing to 30 mg; for a total of eight cycles, plus four additional cycles of glofitamab monotherapy) or R-GemOx (intravenous gemcitabine 1000 mg/m 2 and oxaliplatin 100 mg/m 2 plus rituximab 375 mg/m 2 ; for a total of eight cycles). The trial independent review committee, which evaluated all response-based endpoints, was masked to treatment assignment. The primary endpoint was overall survival. Efficacy analyses were by intention to treat in all randomly assigned patients. We present results from both the primary analysis (cutoff: March 29, 2023) and updated analysis after all patients had completed study therapy (cutoff: Feb 16, 2024). Safety analyses included all patients who received any study treatment. This study is registered with ClinicalTrials.gov, NCT04408638, and is ongoing (closed to recruitment)., Findings: From Feb 23, 2021, to March 14, 2023, 274 patients were enrolled and randomly assigned to receive Glofit-GemOx (n=183) or R-GemOx (n=91). 158 (58%) patients were male and 116 (42%) were female; median age was 68 years (IQR 58-74). At the primary analysis after a median follow-up of 11·3 months (95% CI 9·6-12·7), overall survival was significantly improved with Glofit-GemOx versus R-GemOx (median not estimable [NE; 95% CI 13·8 months-NE] vs 9·0 months [7·3-14·4]; hazard ratio [HR] 0·59 [95% CI 0·40-0·89]; p=0·011). At the updated analysis after a median follow-up of 20·7 months (19·9-23·3), a consistent improvement in overall survival was observed with Glofit-GemOx versus R-GemOx (median 25·5 months [18·3-NE] vs 12·9 months [7·9-18·5]; HR 0·62 [0·43-0·88]). In the safety sets, 180 (100%) patients in the Glofit-GemOx group and 84 (96%) of 88 patients in the R-GemOx group had at least one adverse event during the study period. Cytokine release syndrome occurred in 76 (44%) of 172 glofitamab-exposed patients and was predominantly low grade. Deaths related to glofitamab or rituximab occurred in five (3%) patients in the Glofit-GemOx group and in one (1%) patient in the R-GemOx group., Interpretation: Glofit-GemOx had a significant overall survival benefit compared with R-GemOx, supporting its use in transplant-ineligible patients with relapsed or refractory diffuse large B-cell lymphoma after one or more previous lines of therapy., Funding: F Hoffmann-La Roche., Competing Interests: Declaration of interests JSA has received grants or contracts from BMS, Cellectis, Merck, Mustang Bio, Regeneron, and Seagen; consulting fees from AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, BMS, Celgene, Cellectar, Caribou Biosciences, Century Therapeutics, Celgene, Epizyme, Foresight Diagnostics, Genentech, Gilead, Interius, Lilly, F Hoffmann-La Roche, Seagen, and Takeda; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, AstraZeneca, BMS, Incyte, Janssen, MorphoSys, Novartis, and Regeneron. MKu has received grants or contracts and consulting fees from and participated on a data safety monitoring board or advisory board for F Hoffmann-La Roche; a grant from BeiGene; and consulting fees from AbbVie. MH has received grants from Janssen and F Hoffmann-La Roche; consulting fees from Takeda, F Hoffmann-La Roche, Otsuka, AbbVie, and Gilead; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Takeda, F Hoffmann-La Roche, Otsuka, AbbVie, Gilead, and Pfizer; and participated on a data safety monitoring board or advisory board for Takeda, F Hoffmann-La Roche, Otsuka, AbbVie, and Gilead. CPF has received grants or contracts from BeiGene, F Hoffmann-La Roche, Genmab, and AbbVie; consulting fees from AbbVie, AstraZeneca, Atarabio, BMS, Genmab, Gilead, Kite, Incyte, Janssen, Lilly, Morphosys, Ono, F Hoffmann-La Roche, SERB, and SOBI; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, AstraZeneca, Atarabio, BMS, GenMab, Gilead, Kite, Incyte, Janssen, Lilly, Morphosys, Ono, F Hoffmann-La Roche, SERB, SOBI, and Takeda; and participated on a data safety monitoring board or advisory board for AbbVie, AstraZeneca, Atarabio, BMS, GenMab, Gilead, Kite, Incyte, Janssen, Lilly, Morphosys, Ono, F Hoffmann-La Roche, SERB, and SOBI. DHY has received grants or contracts from AbbVie, BeiGene, Boryung, Celltrion, Kyowa Kirin, Janssen, Samyang, and Sanofi; consulting fees from Abclon, BeiGene, BMS, GI Cell, GC Cell, Verismo, Janssen, Novartis, F Hoffmann-La Roche, and Pharos Bio; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, Antengene, BMS, Boryung, GSK, Kyowa Kirin, Novartis, F Hoffmann-La Roche, Takeda, and Janssen; and participated on a data safety monitoring board or advisory board for Abclon, BeiGene, BMS, GI Cell, GC Cell, Verismo, Janssen, Novartis, F Hoffmann-La Roche, and Pharos Bio. HA has received grants or contracts from Morphosys, Genentech, Novartis, BMS, Epizyme, and Pfizer; consulting fees from Amgen, Genentech, Morphosys, Novartis, BMS, AstraZeneca, Acrotech, ADC Therapeutics, and AbbVie; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Genentech; and participated on a data safety monitoring board or advisory board for Amgen, Genentech, Morphosys, Novartis, BMS, AstraZeneca, Acrotech, ADC Therapeutics, and AbbVie. WT has received grants or contracts and support for attending meetings or travel from F Hoffmann-La Roche; consulting fees from and participated on a data safety monitoring board or advisory board for F Hoffmann-La Roche, Takeda, AbbVie, Sobi, and Gilead; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from F Hoffmann-La Roche, Takeda, Gilead, and AbbVie; and is grateful for and acknowledges funding and support from the University College London Hospitals NHS Foundation Trust Biomedical Research Centre. CH has received grants or contracts from Takeda; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from F Hoffmann-La Roche, Janssen-Cilag, AbbVie, and Gilead; and support for attending meetings or travel from Janssen-Cilag, AbbVie, and F Hoffmann-La Roche. JMZ has received consulting fees from and participated on a data safety monitoring board or advisory board for Pierre Fabre, Takeda, BMS, Gilead, Novartis, Pfizer, Amgen, F Hoffmann-La Roche, AstraZeneca, and AbbVie; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Takeda, F Hoffmann-La Roche, and AbbVie; and support for attending meetings or travel from F Hoffmann-La Roche and AbbVie. CYC has received grants or contracts from BMS, F Hoffmann-La Roche, AbbVie, MSD, and Lilly; consulting fees from F Hoffmann-La Roche, Janssen, Gilead, AstraZeneca, Lilly, BeiGene, Menarini, Dizal, AbbVie, Genmab, and BMS; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from F Hoffmann-La Roche, Janssen, Gilead, AstraZeneca, Lilly, BeiGene, Menarini, Dizal, AbbVie, Genmab, and BMS; and participated on a data safety monitoring board or advisory board for F Hoffmann-La Roche, Janssen, Gilead, AstraZeneca, Lilly, BeiGene, Menarini, Dizal, AbbVie, Genmab, and BMS. HG has received consulting fees from F Hoffmann-La Roche, BMS, and Takeda; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Gilead, F Hoffmann-La Roche, BMS, AbbVie, and Takeda. SS is an employee of and has received grants or contracts from Genentech; and has stock or stock options with F Hoffmann-La Roche. VO-N is an employee of Genentech and has provided all support for the present manuscript for Genentech and F Hoffmann-La Roche. RT is an employee of Genentech and has provided all support for the present manuscript for, has received support for attending meetings or travel from, and has stock or stock options with Genentech and F Hoffmann-La Roche. JR is an employee of and has received grants or contracts from F Hoffmann-La Roche, and has stock or stock options with F Hoffmann-La Roche. MD is an employee of, has provided all support for the present manuscript for, and has stock or stock options with F Hoffmann-La Roche. MKa is an employee of F Hoffmann-La Roche, and has received grants or contracts from Roche Diagnostics International and F Hoffmann-La Roche. EM is an employee of, has received grants or contracts from, has received support for attending meetings or travel from, and has stock or stock options with F Hoffmann-La Roche. HH is an employee of F Hoffmann-La Roche. LL is an employee of, has received grants or contracts from, has received royalties or licences from, has patents planned, issued or pending with, and has stock or stock options with F Hoffmann-La Roche. GPG has received grants or contracts from BeiGene and Merck; consulting fees from Merck, Gilead, Novartis, BMS, Clinigen, F Hoffmann-La Roche, and Prelude Therapeutics; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Gilead and F Hoffmann-La Roche; and participated on a data safety monitoring board or advisory board for Merck, Gilead, Novartis, BMS, Clinigen, F Hoffmann-La Roche and Prelude Therapeutics. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Rationale: Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are an emerging model for determining drug effects and modeling disease. Specialized devices can generate Extracellular Field Potential (EFP) measurements from these cells, analogous to the ventricular complex of the electrocardiogram., Objective: The objective of this study was to develop an easy-to-use, easy-to-teach, reproducible software tool to measure EFPs., Methods-Results: We present the EFP-Analyzer (EFPA), a semi-automized analyzer for EFP traces, which identifies and averages beats, identifies landmarks, and calculates intervals. We evaluated the tool in an analysis of 358 EFP traces from 22 patient-derived lines. We analyzed spontaneously beating iPSC-CMs, as well as optically paced iPSC-CMs through channelrhodopsin. We developed stringent quality criteria and measured EFP intervals, including Field Potential Duration (FPD). FPD from optically paced iPSC-CMs were shorter than those of spontaneously beating iPSC-CMs (283.7.0±54.2 vs. 293.0±47.5, p: 0.32, respectively). We further analyzed the usability and data replicability of EFPA through an inter-intra observer analysis. Correlation coefficient for inter-reader tangent and threshold measurements for these FPD ranged between r: 0.93-1.00. Bland-Altman plots comparing inter observer results for spontaneously beating and paced iPSC-CMs showed 95% limits of agreement (-13.6 to 19.4ms and -13.2 to 15.3ms, respectively). The EFP-analyzer could accurately detect FPD prolongation due to drug (moxifloxacin) or pathogenic loss of function mutations ( CACNA1C N639T). This program is available for download at https://github.com/kroncke-lab/EFPA . The instructions will be available at the same listed website under the README section of the Github main page., Conclusions: The EFP-Analyzer tool is a useful tool that enables the efficient use of iPSC-CMs as a model to study drug effects and disease.

Mosunetuzumab, a CD20xCD3 T-cell engaging bispecific antibody, redirects T cells to eliminate malignant B cells. We present updated efficacy and safety data of a pivotal phase 1/2 study after a median follow-up of 37.4 months in 90 patients with relapsed/refractory (R/R) follicular lymphoma (FL) and ≥2 prior lines of therapy treated with fixed-duration mosunetuzumab. Investigator-assessed complete response (CR) rate and objective response rate (ORR) were 60.0% (95% confidence interval [CI], 49.1-70.2) and 77.8% (95% CI, 67.8-85.9), respectively. Among 70 responders, median duration of response was 35.9 months (95% CI, 20.7-not estimable [NE]). Among 54 patients who achieved CR, 49 remained in CR at the end of treatment; median duration of complete response was not reached (NR) (95% CI, 33.0-NE); Kaplan-Meier-estimated 30-month remission rate was 72.4% (95% CI, 59.2-85.6). Estimated 36-month overall survival (OS) rate was 82.4% (95% CI, 73.8-91.0); median OS was NR (95% CI, NE-NE). Median progression-free survival was 24.0 months (95% CI, 12.0-NE). Median time to CD19+ B-cell recovery was 18.4 months (95% CI, 12.8-25.0) following 8 cycles of mosunetuzumab treatment. No new cytokine release syndrome events or fatal, serious, or Grade ≥3 adverse events were reported. With extended follow-up, mosunetuzumab demonstrated high response rates, durable remissions and manageable safety with no long-term concerns. This supports outpatient mosunetuzumab administration as an off-the-shelf, fixed-duration, safe and effective treatment for patients with R/R FL, including those with high-risk disease. Trial registration: www.clinicaltrials.gov (NCT02500407)., (Copyright © 2024 American Society of Hematology.)

Schizophrenia (SCZ) is a neuropsychiatric disorder, caused by a combination of genetic and environmental factors. The etiology behind the disorder remains elusive although it is hypothesized to be associated with the aberrant response to neurotransmitters, such as dopamine and glutamate. Therefore, investigating the link between dysregulated metabolites and distorted neurodevelopment holds promise to offer valuable insights into the underlying mechanism of this complex disorder. In this study, we aimed to explore a presumed correlation between the transcriptome and the metabolome in a SCZ model based on patient-derived induced pluripotent stem cells (iPSCs). For this, iPSCs were differentiated towards cortical neurons and samples were collected longitudinally at various developmental stages, reflecting neuroepithelial-like cells, radial glia, young and mature neurons. The samples were analyzed by both RNA-sequencing and targeted metabolomics and the two modalities were used to construct integrative networks in silico. This multi-omics analysis revealed significant perturbations in the polyamine and gamma-aminobutyric acid (GABA) biosynthetic pathways during rosette maturation in SCZ lines. We particularly observed the downregulation of the glutamate decarboxylase encoding genes GAD1 and GAD2, as well as their protein product GAD65/67 and their biochemical product GABA in SCZ samples. Inhibition of ornithine decarboxylase resulted in further decrease of GABA levels suggesting a compensatory activation of the ornithine/putrescine pathway as an alternative route for GABA production. These findings indicate an imbalance of cortical excitatory/inhibitory dynamics occurring during early neurodevelopmental stages in SCZ. Our study supports the hypothesis of disruption of inhibitory circuits to be causative for SCZ and establishes a novel in silico approach that enables for integrative correlation of metabolic and transcriptomic data of psychiatric disease models., (© 2024. The Author(s).)

This study focused on addressing the challenges associated with the incompatibility between sulfide solid electrolytes and Ni-rich cathode active materials (CAMs) in all-solid-state lithium-ion batteries. To resolve these issues, protective layers have been explored for Ni-rich materials. Lithium lanthanum titanate (LLTO), a perovskite-type material, is recognized for its excellent chemical stability and ionic conductivity, which render it a potential protective layer in CAMs. However, traditional methods of achieving the perovskite structure involve temperatures exceeding 700 °C, resulting in challenges such as LLTO agglomeration, secondary phase formation between LLTO and CAM, and cation mixing within the CAM. In this study, a rapid technique known as flash-light sintering (FLS) was employed to fabricate a uniform and pure perovskite protective layer without inducing cation mixing within the CAM. The LLTO-coated LiNi 0.8 Co 0.1 Mn 0.1 O 2 (NCM811) with FLS treatment demonstrated minimal cation mixing and formed a fully covered dense layer. This resulted in a high initial capacity and effectively addressed the incompatibility issues between the sulfide electrolytes and CAM. The rapid FLS method not only streamlines the fabrication of LLTO-coated NCM811 but also provides opportunities for its broader application to materials that were previously deemed impractical because of high sintering temperatures.

Background: Dysregulation of iron metabolism is implicated in malignant transformation, cancer progression, and therapeutic resistance. Here, we demonstrate that iron regulatory protein 2 (IRP2) preferentially regulates iron metabolism and promotes tumor growth in colorectal cancer (CRC)., Methods: IRP2 knockdown and knockout cells were generated using RNA interference and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 methodologies, respectively. Cell viability was evaluated using both CCK-8 assay and cell counting techniques. Furthermore, IRP2 inhibition was determined by surface plasmon resonance (SPR) and RNA immunoprecipitation (IP). The suppressive effects of IRP2 were also corroborated in both organoid and mouse xenograft models, providing a comprehensive validation of IRP2's role., Results: We have elucidated the role of IRP2 as a preferential regulator of iron metabolism, actively promoting tumorigenesis within CRC. Elevated levels of IRP2 expression in patient samples are correlated with diminished overall survival, thereby reinforcing its potential role as a prognostic biomarker. The functional suppression of IRP2 resulted in a pronounced delay in tumor growth. Building on this proof of concept, we have developed IRP2 inhibitors that significantly reduce IRP2 expression and hinder its interaction with iron-responsive elements in key iron-regulating proteins, such as ferritin heavy chain 1 (FTH1) and transferrin receptor (TFRC), culminating in iron depletion and a marked reduction in CRC cell proliferation. Furthermore, these inhibitors are shown to activate the AMPK-ULK1-Beclin1 signaling cascade, leading to cell death in CRC models., Conclusions: Collectively, these findings highlight the therapeutic potential of targeting IRP2 to exploit the disruption of iron metabolism in CRC, presenting a strategic advancement in addressing a critical area of unmet clinical need., (© 2024. The Author(s).)

REBa 2 Cu 3 O 7 - x (REBCO, RE = rare earth)-coated conductor is a competitive option in terms of current-carrying capacity and high-stress durability in developing high-field magnets for nuclear magnetic resonance (NMR) research. Meanwhile, a technical challenge in utilizing a stand-alone REBCO NMR magnet is an unexpected difference in the field uniformity between the designed and measured values after being constructed and charged, i.e., harmonic errors. Bortot et al., and Li et al., reported analytic evidence of the related issue. However, sufficient research has not yet been conducted, so evidence should be supplemented further. Here we report harmonic errors due to screening current and inconsistent conductor thickness, confirmed by a 400 MHz 1 H NMR magnet development project. The magnet was first charged up to its operating current, and then multiple overcharge-discharge cycles were applied, which was an empirically optimized operation protocol. A field mapping device obtained magnetic fields at designated locations in the room-temperature bore. The result showed over 100 ppm field uniformity difference between designed and measured values. A simulation model was developed considering screening current and inconsistent conductor thickness for reproducing the field distribution. Comparison of voltages and fields between simulation and measurement validated the model. Further analysis of the overcharge-discharge effect on harmonic errors demonstrated that even and odd-order harmonics are mainly attributed to screening current and geometric inconsistency while confirming the limitation of the screening current mitigation effect. Hence, we concluded that the desirable requirement of the sub-ppm level field uniformity generation might be barely possible with the current REBCO NMR magnet design approach., (© 2024. The Author(s).)

With the success of immunotherapy in cancer, understanding the tumor immune microenvironment (TIME) has become increasingly important; however in pediatric brain tumors this remains poorly characterized. Accordingly, we developed a clinical immune-oncology gene expression assay and used it to profile a diverse range of 1382 samples with detailed clinical and molecular annotation. In low-grade gliomas we identify distinct patterns of immune activation with prognostic significance in BRAF V600E-mutant tumors. In high-grade gliomas, we observe immune activation and T-cell infiltrates in tumors that have historically been considered immune cold, as well as genomic correlates of inflammation levels. In mismatch repair deficient high-grade gliomas, we find that high tumor inflammation signature is a significant predictor of response to immune checkpoint inhibition, and demonstrate the potential for multimodal biomarkers to improve treatment stratification. Importantly, while overall patterns of immune activation are observed for histologically and genetically defined tumor types, there is significant variability within each entity, indicating that the TIME must be evaluated as an independent feature from diagnosis. In sum, in addition to the histology and molecular profile, this work underscores the importance of reporting on the TIME as an essential axis of cancer diagnosis in the era of personalized medicine., (© 2024. The Author(s).)

Purpose: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and large international cooperative efforts are needed to evaluate the significance of clinical risk factors and immunoarchitectural patterns (IAPs) for all stages of pediatric and adult patients with NLPHL., Methods: Thirty-eight institutions participated in the Global nLPHL One Working Group retrospective study of NLPHL cases from 1992 to 2021. We measured progression-free survival (PFS), overall survival (OS), transformation rate, and lymphoma-specific death rate. We performed uni- and multivariable (MVA) Cox regression stratified by management to select factors for the lymphocyte-predominant international prognostic score (LP-IPS) validated by five-fold cross-validation., Results: We identified 2,243 patients with a median age of 37 years (IQR, 23-51). The median follow-up was 6.3 years (IQR, 3.4-10.8). Most had stage I to II (72.9%) and few B symptoms (9.9%) or splenic involvement (5.4%). IAP was scored for 916 (40.8%). Frontline management included chemotherapy alone (32.4%), combined modality therapy (30.5%), radiotherapy alone (24.0%), observation after excision (4.6%), rituximab alone (4.0%), active surveillance (3.4%), and rituximab and radiotherapy (1.1%). The PFS, OS, transformation, and lymphoma-specific death rates at 10 years were 70.8%, 91.6%, 4.8%, and 3.3%, respectively. On MVA, IAPs were not associated with PFS or OS, but IAP E had higher risk of transformation (hazard ratio [HR], 1.81; P < .05). We developed the LP-IPS with 1 point each for age ≥45 years, stage III-IV, hemoglobin <10.5 g/dL, and splenic involvement. Increasing LP-IPS was significantly associated with worse PFS (HR, 1.52) and OS (HR, 2.31) and increased risk of lymphoma-specific death (HR, 2.63) and transformation (HR, 1.41)., Conclusion: In this comprehensive study of all ages of patients with NLPHL, we develop the LP-IPS to identify high-risk patients and inform upcoming prospective clinical trials evaluating de-escalation of therapy for patients with low LP-IPS scores (<2).

Background: Despite recent advances, optimal therapeutic approaches applicable to subpopulations with primary central nervous system (CNS) lymphoma outside of clinical trials remain to be determined., Methods: We performed a retrospective study of immunocompetent, adult patients with histologically confirmed diffuse large B-cell lymphoma of the CNS (PCNSL). 190/204 (93%) patients (median age: 65) received one of five high-dose methotrexate (HD-MTX) containing chemotherapy regimens: MPV/Ara-C (HD-MTX, procarbazine, and vincristine, followed by cytarabine [Ara-C]) ( n  = 94, 50%), MATRix (HD-MTX, Ara-C, thiotepa, and rituximab) ( n  = 19, 10%), HD-MTX/Ara-C ( n  = 31, 16%), HD-MTX monotherapy ( n  = 35, 18%) and MBVP (HD-MTX, carmustine, teniposide, prednisolone) ( n  = 11, 6%)., Results: Cumulative median HD-MTX and Ara-C doses were 17 g/m 2 (range: 1-64 g/m 2 ) and 12 g/m 2 (0-32 g/m 2 ) respectively. Using 14 g/m 2 as the reference dose, the median HD-MTX relative dose intensity (HD-MTX-RDI) was 1.25 (0.27-4.57) with 84% receiving > 0.75. The overall response rate (ORR) was 72% (complete response: 50%) after completing HD-MTX. At a median follow-up of 3.41 years (0.06-9.42), progression-free survival (PFS) and overall survival (OS) were different between chemotherapy cohorts, with the best outcomes achieved in the MPV/Ara-C cohort (2-year PFS 74%, 2-year OS 82%; p  = 0.0001 and p  = 0.0024 respectively). On multivariate analysis, MPV/Ara-C administration and HD-MTX-RDI > 0.75 were associated with longer PFS and OS., Conclusion: Sequential, response-adapted approaches can improve outcomes, even in older patients who are ineligible for a high-intensity concurrent chemotherapy approach and do not undergo traditional consolidative strategies., Competing Interests: Katharine Louise Lewis: Consultancy/Honoraria: Jansen Roche. Trial steering committee: Loxo/Lilly. Advisory: IQVIA and MSD; Pietro R. Di Ciaccio: Honoraria/travel funding: Janssen, Astra Zeneca, and Gilead/Kite; Chan Y. Cheah: Research funding: Beigene. Advisory: Janssen Cilag. Joel Wight: Honoraria: Janssen, MDI, Beigene, MSD, and Abbvie. Travel support: Kite/Gilead. Jake Shortt: Consultancy: BMS, Otsuka, Pfizer, and Astellas. Speaker's Bureau: Mundipharma and Novartis. Research funding: Astex. Dipti Talaulikar: Consultancy/Advisory/Honoraria: Roche, Janssen, Beigene, Novartis, Amgen, Antengene, CSL, EUSA, BMS, and Takeda. Research funding: Roche, Janssen, and Takeda. Tara Cochrane: Research funding: Beigene. Advisory: Janssen Cilag. Eliza A. Hawkes: Consultancy/Advisory: AstraZeneca, Janssen Oncology, Merck Sharpe & Dohme, Gilead Sciences, Bristol Myers Squibb, Novartis, Beigene, Link Healthcare, and Regeneron. Speaker's Bureau: Roche/Genentech, Regeneron, and Abbvie. Research funding: AstraZeneca, Celgene, Merck KGaA, Janssen‐Cilag, Gilead Sciences, Mundipharma, Bristol‐Myers Squibb, and Roche/Genentech. Travel: AstraZeneca., (© 2024 The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

In the early COVID-19 pandemic with urgent need for countermeasures, we aimed at developing a replicating viral vaccine using the highly efficacious measles vaccine as vector, a promising technology with prior clinical proof of concept. Building on our successful pre-clinical development of a measles virus (MV)-based vaccine candidate against the related SARS-CoV, we evaluated several recombinant MV expressing codon-optimized SARS-CoV-2 spike glycoprotein. Candidate V591 expressing a prefusion-stabilized spike through introduction of two proline residues in HR1 hinge loop, together with deleted S1/S2 furin cleavage site and additional inactivation of the endoplasmic reticulum retrieval signal, was the most potent in eliciting neutralizing antibodies in mice. After single immunization, V591 induced similar neutralization titers as observed in sera of convalescent patients. The cellular immune response was confirmed to be Th1 skewed. V591 conferred long-lasting protection against SARS-CoV-2 challenge in a murine model with marked decrease in viral RNA load, absence of detectable infectious virus loads, and reduced lesions in the lungs. V591 was furthermore efficacious in an established non-human primate model of disease (see companion article [S. Nambulli, N. Escriou, L. J. Rennick, M. J. Demers, N. L. Tilston-Lunel et al., J Virol 98:e01762-23, 2024, https://doi.org/10.1128/jvi.01762-23]). Thus, V591 was taken forward into phase I/II clinical trials in August 2020. Unexpected low immunogenicity in humans (O. Launay, C. Artaud, M. Lachâtre, M. Ait-Ahmed, J. Klein et al., eBioMedicine 75:103810, 2022, https://doi.org/10.1016/j.ebiom.2021.103810) revealed that the underlying mechanisms for resistance or sensitivity to pre-existing anti-measles immunity are not yet understood. Different hypotheses are discussed here, which will be important to investigate for further development of the measles-vectored vaccine platform.IMPORTANCESARS-CoV-2 emerged at the end of 2019 and rapidly spread worldwide causing the COVID-19 pandemic that urgently called for vaccines. We developed a vaccine candidate using the highly efficacious measles vaccine as vector, a technology which has proved highly promising in clinical trials for other pathogens. We report here and in the companion article by Nambulli et al. (J Virol 98:e01762-23, 2024, https://doi.org/10.1128/jvi.01762-23) the design, selection, and preclinical efficacy of the V591 vaccine candidate that was moved into clinical development in August 2020, 7 months after the identification of SARS-CoV-2 in Wuhan. These unique in-human trials of a measles vector-based COVID-19 vaccine revealed insufficient immunogenicity, which may be the consequence of previous exposure to the pediatric measles vaccine. The three studies together in mice, primates, and humans provide a unique insight into the measles-vectored vaccine platform, raising potential limitations of surrogate preclinical models and calling for further refinement of the platform., Competing Interests: J. Brunet, Z.C., M.G., H.S.-M., M.M., P.C., L. Majlessi, C.G., A.M., and N.E. are inventors of a patent application describing measles-vectored vaccine candidates against SARS-CoV-2. All other authors declare no financial or non-financial competing interests.

Resting-state alpha brain rhythms provide a foundation for basic as well as higher-order brain processes. Research suggests atypical maturation of the peak frequency of resting-state alpha activity (= PAF) in autism spectrum disorder (ASD). The present study examined resting-state alpha activity in young school-aged children, obtaining magnetoencephalographic (MEG) eyes-closed resting-state data from 47 typically developing (TD) males and 45 ASD males 6.0 to 9.3 years old. Results confirmed a higher PAF in ASD versus TD, and demonstrated that alpha power differences between groups were linked to the shift of PAF in ASD. Additionally, a higher PAF was associated with better cognitive performance in TD but not ASD. Finding thus suggested functional consequences of group differences in resting-state alpha activity., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

Background: Highly emetogenic chemotherapy (HEC) is known to induce nausea and vomiting (CINV) in approximately 90% of cancer patients undergoing this regimen unless proper prophylactic antiemetics are administered. This study aimed to analyze the use of a three-drug prophylactic antiemetic regimen during the first cycle of chemotherapy and assess the compliance rate with the National Comprehensive Cancer Network (NCCN) guidelines., Methods: This retrospective study utilized data from the National Inpatient Sample database from 2016 to 2020 provided by the Health Insurance Review and Assessment Service. The claims data encompassed 10 to 13% of inpatients admitted at least once each year. Patients with solid cancers treated with two HEC regimens, namely anthracycline + cyclophosphamide (AC) and cisplatin-based regimens, were selected as the study population. We evaluated the use of a three-drug prophylactic antiemetic regimen, including a neurokinin-1 receptor antagonist, a 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone and compliance with the NCCN guidelines. Multiple logistic regression was conducted to estimate the influence of variables on guideline adherence., Results: A total of 3119 patients were included in the analysis. The overall compliance rate with the NCCN guidelines for prophylactic antiemetics was 74.3%, with higher rates observed in the AC group (87.9%) and lower rates in the cisplatin group (60.4%). The AC group had a 6.37 times higher likelihood of receiving guideline-adherent antiemetics than the cisplatin group. Further analysis revealed that, compared to 2016, the probability of complying with the guidelines in 2019 and 2020 was 0.72 times and 0.76 times lower, respectively., Conclusion: This study showed that a considerable proportion of HEC-treated patients received guideline-adherent antiemetic therapies. However, given the variations in adherence rates between different chemotherapy regimens (AC vs. cisplatin), efforts to improve adherence and optimize antiemetic treatment remain essential for providing the best possible care for patients experiencing CINV., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Polatuzumab vedotin (Pola) is an approved therapy in combination with rituximab and bendamustine for relapsed or refractory diffuse large B-cell lymphoma (RR-DLBCL) based on positive results of the landmark phase II randomised G029365 trial. However, trial results for many approved novel therapies in RR-DLBCL have not been replicated in routine care cohorts, as RR-DLBCL patient populations are heterogeneous and trial eligibility is increasingly restrictive. We evaluated outcomes from pola ± bendamustine and rituximab in patients with RR-DLBCL enrolled in a compassionate access program with no alternative treatment options identified via the Australasian Lymphoma and Related Diseases Registry according to their eligibility for the original phase II published study. Of 58 eligible patients, 74% met the criteria deeming them ineligible for the G029365 original study at the time of pola's commencement. Median progression-free survival and overall survival in our cohort were 2.3 and 3.5 months, respectively. In contrast to the landmark trial cohort, more of our patients ceased therapy prior to completion, the majority due to progressive disease and only 8/58 received any subsequent treatment. Dismal outcomes in this Australian real-world population demonstrate trial eligibility is challenging to meet, and newer treatments can be difficult to deliver in routine care. Clinically applicable results from therapeutic studies require trial cohorts to reflect representative clinical populations wherever possible, and more research is required to address the benefit of novel agents in the increasing majority who are ineligible for modern studies., Competing Interests: Briony Shaw, Eliza Chung, Edward Yoo, Rory Bennett, Callum Birks, Jock Simpson, Sumita Ratnasingam, Tasman Armytage, Denise Lee, Colm Keane, Stephanie Wallwork all declare no conflicts of interest. Anna Johnston: Consulting or advisory role, honoraria: Merck Sharpe & Dohme, Roche, Link, BeiGene, Sanofi, EUSA Pharma, Novartis, Chan Y Cheah: Consulting or advisory role, honoraria: Roche, Janssen, Gilead, AstraZenecca, Lilly, TG therapeutics, BeiGene, Novartis, Menarini, Dizal, AbbVie, Genmab, Bristol Myers Quibb; Research funding: Bristol Myers Quibb, Roche, AbbVie, Merck Sharpe & Dohme, Lilly, Nada Hamad: Honoraria: Roche, Janssen, Gilead, AstraZenecca, BeiGene, Novartis, AbbVie, Genmab, Bristol Myers Quibb, Takeda, Jazz Pharmaceuticals, Incyte, Pfizer, Mallinckrodt Pharmaceuticals, Terumo, Allison Barraclough: Honoraria: Roche, Gilead, Novartis, BeiGene, Matthew Ku: Roche, Antengene, Genor BioPharma, Nicholas Viiala: Honoraria and advisory board: Novartis, Tara Cochrane: Consulting or advisory role: Janssen; Honoraria: Celgene (in 2019); Research funding: BeiGene, Geoffrey Chong: Research funding: Bristol Myers Quibb, Merck, AstraZeneca, Pharmacyclics, Regeneron, Hutchmed, Bayer, Incyte, Amgen, Kate Manos: Advisory/honoraria: AbbVie; Research funding: Roche, Stephen Opat: Honoraria: AbbVie, BeiGene, AstraZeneca, Bristol Myers Quibb, CSL Behring, Gilead, Janssen, Merck, Roche, Takeda; Research funding: AbbVie, BeiGene, AstraZeneca, CSL Behring, Gilead, Janssen, Merck, PharmaCytics, Roche, Takeda, Eliza A. Hawkes: Consulting or advisory role: Roche, Merck Sharpe & Dohme, AstraZeneca, Gilead, Antengene, Novartis, Regeneron, Janssen, Specialised Therapeutics; Research funding: Roche, Bristol Myers Squibb, Merck KGaA, AstraZeneca, Merck, (© 2024 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

In this study, a SiO 2 layer-coated g-C 3 N 4 catalyst was prepared by a sol-gel method to overcome the poor adsorption ability and high recombination rate of charge carriers of pristine g-C 3 N 4 . SEM and TEM images indicated that SiO 2 nanoparticles were coated on the surface of g-C 3 N 4 nanoparticles with a layered structure and the layers were tightly contacted with g-C 3 N 4 . XRD patterns, FTIR spectra, UV-vis spectra and XPS spectra revealed that the structure of g-C 3 N 4 was not destroyed and its photoelectric catalytic properties were not suppressed by the coating of SiO 2 layers. Adsorption experiments revealed that the SiO 2 layers improved the adsorption performance of g-C 3 N 4 and their ratios were adjusted. The molecular weights of the final products of the degradation of RhB and antibiotics were at the micro-molecule level while the amount of g-C 3 N 4 reached 1.2% of the mass fraction, which were more suitable for pollutant degradation compared with those of g-C 3 N 4 due to its poor adsorption ability. The reason for this was likely that the SiO 2 layers were not only beneficial for the adsorption of pollutants and intermediate products but also for prolonging the life time of the separated electrons and holes. Finally, active trapping experiments confirmed that both the holes and superoxide radicals were the main factors in the degradation of RhB and antibiotics, with the superoxides being the most active species., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Despite widespread vaccination rates, we are living with high transmission rates of SARS-CoV-2. Although overall hospitalisation rates are falling, the risk of serious infection remains high for patients who are immunocompromised because of haematological malignancies. In light of the ongoing pandemic and the development of multiple agents for treatment, representatives from the Haematology Society of Australia and New Zealand and infectious diseases specialists have collaborated on this consensus position statement regarding COVID-19 management in patients with haematological disorders. It is our recommendation that both patients with haematological malignancies and treating specialists be educated regarding the preventive and treatment options available and that patients continue to receive adequate vaccinations, keeping in mind the suboptimal vaccine responses that occur in haematology patients, in particular, those with B-cell malignancies and on B-cell-targeting or depleting therapy. Patients with haematological malignancies should receive treatment for COVID-19 in accordance with the severity of their symptoms, but even mild infections should prompt early treatment with antiviral agents. The issue of de-isolation following COVID-19 infection and optimal time to treatment for haematological malignancies is discussed but remains an area with evolving data. This position statement is to be used in conjunction with advice from infectious disease, respiratory and intensive care specialists, and current guidelines from the National COVID-19 Clinical Evidence Taskforce and the New Zealand Ministry of Health and Cancer Agency Te Aho o Te Kahu COVID-19 Guidelines., (© 2023 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma characterised by a heterogeneous clinical course. Patients can often receive sequential treatments, yet these typically yield diminishing periods of disease control, raising questions about optimal therapy sequencing. Novel agents, such as chimeric antigen receptor T-cell therapies and bispecific antibodies, show promise in relapsed MCL, but are often reserved for later treatment lines, which may underserve patients with aggressive disease phenotypes who die early in the treatment journey. To assess the problem of patient attrition from lymphoma-related death limiting sequential treatment, we performed a multicentre retrospective cohort analysis of 389 patients treated at Australian and UK centres over a 10-year period. Deaths from MCL increased after each treatment line, with 7%, 23% and 26% of patients dying from uncontrolled MCL after first, second and third lines respectively. Patients with older age at diagnosis and early relapse after induction therapy were at particular risk of death after second-line treatment. This limitation of sequential treatment by lymphoma-related death provides support for the trial of novel therapies in earlier treatment lines, particularly in high-risk patient populations., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Abstract: Plasmablastic lymphoma (PBL) is a rare and aggressive non-Hodgkin lymphoma associated with immunodeficiency, characterized by uncertain treatment approaches and an unfavorable prognosis. We conducted a multicenter, international, retrospective cohort study, aiming to characterize the clinical features, risk factors, and outcomes of patients with PBL. Data were collected from 22 institutions across 4 countries regarding patients diagnosed with PBL between 1 January 1999 and 31 December 2020. Survival risk factors were analyzed using both univariate and multivariate regression models. Overall survival (OS) was calculated using Kaplan-Meier statistics. First-line treatment regimens were stratified into standard- and higher-intensity regimens, and based on whether they incorporated a proteasome inhibitor (PI). A total of 281 patients (median age, 55 years) were included. Immunodeficiency of any kind was identified in 144 patients (51%), and 99 patients (35%) had HIV-positive results. The 5-year OS for the entire cohort was 36% (95% confidence interval, 30%-42%). In multivariate analysis, inferior OS was associated with Epstein-Barr virus-negative lymphoma, poor performance status, advanced stage, and bone marrow involvement. In an independent univariate analysis, the international prognostic index was associated with OS outcomes. Neither immunosuppression nor HIV infection, specifically, influenced OS. Among patients treated with curative intent (n = 234), the overall response rate was 72%. Neither the intensity of the treatment regimen nor the inclusion of PIs in first-line therapy was associated with OS. In this large retrospective study of patients with PBL, we identified novel risk factors for survival. PBL remains a challenging disease with poor long-term outcomes., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Oncogenic fusion genes may be identified from next-generation sequencing data, typically RNA-sequencing. However, in a clinical setting, identifying these alterations is challenging against a background of nonrelevant fusion calls that reduce workflow precision and specificity. Furthermore, although numerous algorithms have been developed to detect fusions in RNA-sequencing, there are variations in their individual sensitivities. Here this problem was addressed by introducing MetaFusion into clinical use. Its utility was illustrated when applied to both whole-transcriptome and targeted sequencing data sets. MetaFusion combines ensemble fusion calls from eight individual fusion-calling algorithms with practice-informed identification of gene fusions that are known to be clinically relevant. In doing so, it allows oncogenic fusions to be identified with near-perfect sensitivity and high precision and specificity, significantly outperforming the individual fusion callers it uses as well as existing clinical-grade software. MetaFusion enhances clinical yield over existing methods and is able to identify fusions that have patient relevance for the purposes of diagnosis, prognosis, and treatment., Competing Interests: Disclosure Statement None declared., (Copyright © 2023 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Carotenoids, such as lycopene and β-carotene, have been widely recognized for their antioxidant properties and potential health benefits. Accurate quantification of carotenoids in plant extracts is essential for nutritional assessment, quality control, and research investigations. This study introduces an innovative method for quantifying lycopene and β-carotene, in plant extracts and aims to bridge the gap between complex and expensive carotenoid quantification techniques and the need for accessible methods that can be widely adopted. The primary difference between HPLC and HPTLC lies in the medium used for separation. HPLC employs a liquid phase within columns, while HPTLC utilizes a thin layer of adsorbent on a plate. This distinction impacts factors like equipment, cost, and analysis time. The VisionCats software, combined with the CAMAG Visualizer-2, allows the semi-quantification of metabolites using an image-based evaluation method enabling the simultaneous assessment of qualitative and semi-quantitative information from the HPTLC images. Sample preparation involves washing and drying the vegetal material, followed by dichloromethane extraction. HPTLC analysis is performed using the CAMAG Advanced Herbal System, and the validation studies include establishing calibration curves and determining the detection threshold and minimum quantification threshold for lycopene and β-carotene. Specificity and precision were evaluated to ensure accurate identification and repeatability of the method. Data analysis involves selecting the regression method based on the nature of the data and assessing the goodness of fit using the R2 value. The results showed distinct peaks corresponding to lycopene and β-carotene in the chromatograms of the plant extract samples. The visualizer-based method demonstrates good specificity and precision, with no interfering peaks observed and low relative standard deviation. The method shows promising results regarding specificity, precision, and reliability. It has the potential for broader implementation in carotenoid research and rapid monitoring of carotenoid content in various agricultural and food products, particularly in resource-limited settings. Further optimization and validation on a wider range of samples would enhance the applicability of this method in carotenoid research. Sample preparation involves washing and drying the vegetal material, followed by dichloromethane extraction. HPTLC analysis is performed using the CAMAG Advanced Herbal System, and the validation studies include establishing calibration curves and determining the detection threshold and minimum quantification threshold for lycopene and β-carotene. Specificity and precision were evaluated to ensure accurate identification and repeatability of the method. Data analysis involves selecting the regression method based on the nature of the data and assessing the goodness of fit using the R2 value. The results showed distinct peaks corresponding to lycopene and β-carotene in the chromatograms of the plant extract samples. The visualizer-based method demonstrates good specificity and precision, with no interfering peaks observed and low relative standard deviation. The method shows promising results regarding specificity, precision, and reliability. It has the potential for broader implementation in carotenoid research and for rapid screening and monitoring of carotenoid content in various agricultural and food products, particularly in resource-limited settings. Further optimization and validation on a wider range of samples would enhance the applicability of this method in carotenoid research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)