PubMed Daily Triage — 2026-10-24

Run ID: 2026-10-24-attempt1-20261024T090000Z
CRDT Window: 2026-10-23T09:00:00Z → 2026-10-24T09:00:00Z
Articles scored: 22 | HIGH: 8 | STANDARD: 9 | LOW: 5

🔴 HIGH PRIORITY (8 articles)

1. Sequential diagnosis with language models

PMID: 42912144 | Journal: Science | Date: 2026-10-22 | Score: 9/10 | 🔒 Paywalled
Topics: ai_ml_clinical_diagnostics
DOI: 10.1126/science.aeh7930
Design: Benchmark study | Model: computational | Maturity: emerging
Score breakdown: novelty=3/3, relevance=3/3, design_quality=2/2, population_need=1/2

Key finding: A frontier AI physician-panel simulator achieved 83.2% diagnostic accuracy on NEJM CPC cases and 80.3% on MIMIC-IV ED admissions, substantially outperforming generalist physicians (36.1% and 46.8%), by iteratively acquiring information and selecting cost-effective tests.

Summary: A Microsoft research team developed an AI system that simulates a physician panel in iterative sequential diagnosis, incrementally acquiring clinical information and selecting cost-effective tests to reach differential diagnoses. Evaluated on two independent benchmarks—NEJM clinicopathological conference cases and real emergency department admissions from MIMIC-IV—the system achieved 83.2% and 80.3% accuracy, substantially exceeding generalist physician performance (36.1% and 46.8%).

Triage reason: High-impact Science publication demonstrating frontier language model performance in sequential diagnostic reasoning surpassing specialist physicians across two independent benchmarks; immediately applicable to clinical AI decision-support system design and deployment.

Confidence: high
Authors: Nori H, Daswani M, Kelly C, Lundberg S, Ribeiro MT, Wilson M...

2. Ravulizumab in IgA Nephropathy - Interim Analysis of a Phase 3 Trial

PMID: 42912700 | Journal: N Engl J Med | Date: 2026-10-23 | Score: 9/10 | 🔒 Paywalled
Topics: rare_diseases_high_unmet_need
DOI: 10.1056/NEJMoa2607544
Design: Phase 3 RCT (interim analysis) | Model: human | Maturity: mature
Score breakdown: novelty=3/3, relevance=2/3, design_quality=2/2, population_need=2/2

Key finding: Ravulizumab (C5 complement inhibitor, IV every 8 weeks) produced a 43.4% greater reduction in 24-hour urinary protein-to-creatinine ratio vs placebo at Week 34 in adults with IgA nephropathy (P<0.001), with fewer serious adverse events (4.6% vs 9.0%) and no meningococcal infections.

Summary: In a Phase 3 RCT (I CAN trial, n=485) of adults with IgA nephropathy and persistent proteinuria on standard therapy, ravulizumab—a long-acting terminal complement C5 inhibitor administered IV every 8 weeks—was compared to placebo. At the prespecified Week 34 interim analysis, ravulizumab produced a 43.4% greater geometric mean reduction in urinary protein-to-creatinine ratio (P<0.001), with a favorable safety profile and no meningococcal infections or deaths.

Triage reason: High-impact NEJM Phase 3 interim analysis demonstrating significant complement C5 inhibition efficacy in IgA nephropathy—a rare progressive kidney disease with high unmet need—representing a potentially practice-changing mechanism-based treatment supported by robust RCT data.

Confidence: high
Authors: Barratt J, Farag YMK, Rice K, Cammett TJ, Inker LA, Trimarchi H...

3. CD8 T-cell exhaustion linked with CAR T-cell failure can be mitigated by a non-alpha IL2 receptor agonist

PMID: 42913488 | Journal: Blood | Date: 2026-10-23 | Score: 9/10 | 🔒 Paywalled
Topics: hematologic_malignancies, novel_therapeutics
DOI: 10.1182/blood.2026033885
Design: Preclinical (scRNA-seq, in vitro, patient-derived in vivo model) | Model: mixed | Maturity: emerging
Score breakdown: novelty=3/3, relevance=3/3, design_quality=1/2, population_need=2/2

Key finding: scRNA-seq of post-CART19 progressive tumors revealed clonally expanded but transcriptionally exhausted CART19 cells with reduced IL2 signaling; pegenzileukin (non-alpha IL2R agonist) prevented dysfunction in vitro and achieved complete tumor eradication, including CNS relapse clearance, in a patient-derived in vivo model.

Summary: Single-cell RNA-sequencing of tumors from CART19 non-responders revealed clonally expanded but transcriptionally exhausted CART19 cells with chronic stimulation features and reduced IL2 signaling as a key failure mechanism in relapsed/refractory large B-cell lymphoma. Pegenzileukin, a non-alpha IL2 receptor agonist developed by Sanofi, prevented this dysfunction in vitro and achieved complete tumor eradication—including CNS relapse—in a patient-derived in vivo model where CART19 alone produced only transient responses.

Triage reason: Mechanistically rigorous Blood paper from MD Anderson defining T-cell exhaustion as a tractable CART19 failure mechanism with preclinical proof-of-concept for a clinically available agent (pegenzileukin), directly informing combination clinical trial design for relapsed/refractory B-cell lymphoma.

Confidence: high
Authors: Arita K, Dai E, Li X, Sheikh IN, Reville PK, Henderson J...

4. A novel CD123xVdelta2 bispecific T cell engager induces potent and tumor selective Vgamma9Vdelta2-T cell activity against CD123 expressing acute myeloid leukemia and myelodysplastic syndrome

PMID: 42918561 | Journal: Clin Immunol | Date: 2026-10-23 | Score: 9/10 | 🔒 Paywalled
Topics: hematologic_malignancies, novel_therapeutics
DOI: 10.1016/j.clim.2026.110786
Design: Preclinical (in vitro + xenograft + NHP PK); Phase 1 trial initiated | Model: mixed | Maturity: emerging
Score breakdown: novelty=3/3, relevance=3/3, design_quality=1/2, population_need=2/2

Key finding: A humanized half-life-extended CD123xVdelta2 bispecific T-cell engager potently and selectively lysed patient-derived AML/MDS cells via Vgamma9Vdelta2 T cells with lower CRS cytokine induction than CD3-based bispecifics, demonstrated xenograft efficacy with antibody-like PK in primates, and prompted Phase 1 trial initiation (ACTRN12624001214527).

Summary: Researchers developed a CD123xVdelta2 bispecific T-cell engager that redirects Vgamma9Vdelta2 gamma-delta T cells—naturally circulating in blood and bone marrow—against CD123-expressing AML and MDS cells, demonstrating potent tumor-selective lysis even at low effector-to-target ratios and lower CRS-associated cytokines than CD3-based comparators. Efficacy was confirmed in AML xenograft models with antibody-like pharmacokinetics in nonhuman primates, and a Phase 1 clinical trial has been initiated.

Triage reason: Novel gamma-delta T cell-redirecting approach for AML/MDS combining reduced CRS risk with comprehensive preclinical validation including patient-derived cells; Phase 1 initiation signals translational readiness, highly relevant to hematologic malignancy immunotherapy pipeline.

Confidence: high
Authors: Ruben JM, Mousset CM, van de Berg D, Hofman K, de Jong M, Brouwer P...

5. Examining reliance patterns on AI advice in medical imaging: a mixed-methods, randomised, crossover experiment

PMID: 42919730 | Journal: Lancet Digit Health | Date: 2026-10-23 | Score: 9/10 | 🔒 Paywalled
Topics: ai_ml_clinical_diagnostics
DOI: 10.1016/j.landig.2026.101050
Design: Randomized crossover experiment (preregistered) | Model: human | Maturity: developing
Score breakdown: novelty=2/3, relevance=3/3, design_quality=2/2, population_need=2/2

Key finding: In a preregistered randomized crossover study of 125 clinicians reading head CTs, under-reliance on correct AI advice was more detrimental than over-reliance on incorrect advice; explainable AI (scan annotations) improved diagnostic performance vs no advice (OR=1.84, P<0.0001) and was perceived as more useful than basic AI prediction.

Summary: A preregistered mixed-methods randomized crossover experiment enrolled 125 clinicians (50 radiologists, 75 non-radiologist physicians and trainees) who read 50 head CT scans under three conditions: no AI, basic AI prediction, or explainable AI with scan annotations. Under-reliance on correct AI advice had a more detrimental effect on diagnostic performance than over-reliance on incorrect advice; explainable AI significantly improved diagnostic performance (OR=1.84, P<0.0001) and confidence versus no-advice conditions, particularly for difficult hemorrhage cases.

Triage reason: High-quality preregistered Lancet Digital Health RCT identifying under-reliance as the primary AI-clinician risk in radiology and demonstrating explainable AI superiority; findings directly actionable for clinical AI deployment guidelines and human-AI teaming research.

Confidence: high
Authors: Gaube S, Jussupow E, Kokje E, Koch TK, Khan J, Bondi-Kelly E...

6. Gut virome remodeling after fecal microbiota transplantation is associated with virus-bacteria co-variation and metabolic response in obesity and type 2 diabetes

PMID: 42912803 | Journal: Gut Microbes | Date: 2026-10-23 | Score: 8/10 | 🔒 Paywalled
Topics: cardiovascular_metabolic
DOI: 10.1080/19490976.2026.2746820
Design: Randomized Controlled Trial (mechanistic virome sub-study) | Model: human | Maturity: developing
Score breakdown: novelty=2/3, relevance=2/3, design_quality=2/2, population_need=2/2

Key finding: In an FMT RCT in obese adults with T2D, donor-derived viral engraftment occurred in 58.8-64.7% of FMT recipients vs 5.6% sham; post-FMT virome changes predicted LDL response with 84.8% accuracy (comparable to bacteriome 81.4%), implicating Caudoviricetes phages as metabolic mediators.

Summary: In a randomized controlled FMT trial in adults with obesity and type 2 diabetes, virus-like particle-enriched metagenomic sequencing of longitudinal fecal samples showed donor-derived viral engraftment in 58.8-64.7% of FMT recipients versus 5.6% of sham controls, with post-FMT virome changes showing 84.8% accuracy in classifying LDL responders—comparable to bacteriome changes (81.4%). FMT induced increased virome diversity, compositional shifts toward donor virome profiles, and coordinated virus-bacteria co-variation involving Roseburia, Bifidobacterium, Escherichia, Blautia, and Enterococcus, identifying gut viruses as complementary ecological mediators of FMT metabolic benefits.

Triage reason: First mechanistic RCT data linking gut virome remodeling to metabolic outcomes in FMT for obesity/T2D, with random-forest classification showing virome predicts metabolic response comparably to bacteriome; novel angle on gut microbiome-cardiometabolic axis with implications for optimizing FMT protocols.

Confidence: high
Authors: Jiang H, Peng Y, Lam B, Yang K, Lin Y, Mak JWY...

7. mChIP-seq for multiplex epigenomic profiling uncovers cancer-specific histone features in cellular and circulating nucleosomes

PMID: 42913642 | Journal: Cell Rep Methods | Date: 2026-10-22 | Score: 8/10 | 🔓 Open
Topics: early_cancer_detection
DOI: 10.1016/j.crmeth.2026.101641
Design: Methods development / proof-of-concept | Model: human | Maturity: emerging
Score breakdown: novelty=3/3, relevance=2/3, design_quality=1/2, population_need=2/2

Key finding: mChIP-seq simultaneously profiles 11 histone modifications across cancer cell lines revealing reduced H2A.Z-H3K4me3 correlation in cancer; extended to cell-free plasma (cf-mChIP-seq), multiplex profiling of H2A.Z, H3K4me3, H3K27ac, and H3K9me3 in circulating nucleosomes distinguished breast cancer from healthy controls.

Summary: The authors developed multiplexed ChIP-seq (mChIP-seq), a technology compatible with cellular and cell-free samples that simultaneously profiles multiple histone modifications using a one-step sample-indexing pool-and-split strategy, profiling 11 marks across nine cancer types and revealing reduced H2A.Z-H3K4me3 promoter correlation in cancer cells versus non-cancerous controls. Applied to plasma as cell-free mChIP-seq, simultaneous profiling of four histone marks in circulating nucleosomes identified distinct cfDNA fragment patterns distinguishing breast cancer patients from healthy controls, establishing a scalable epigenomic liquid biopsy platform.

Triage reason: Novel Cell Reports Methods paper introducing multiplex epigenomic profiling of circulating nucleosomes as a multi-dimensional liquid biopsy approach; technically sound with breast cancer human sample validation and strong potential for pan-cancer early detection and tissue-of-origin inference.

Confidence: high
Authors: Sun C, Zhang Q, Yan J, Wang X, Zhang C, Li Y...

8. Neoadjuvant nivolumab plus gemcitabine-cisplatin followed by postsurgical adjuvant nivolumab versus neoadjuvant gemcitabine-cisplatin in patients with muscle-invasive bladder cancer: final results from the phase III CA017-078 trial

PMID: 42918420 | Journal: Ann Oncol | Date: 2026-10-23 | Score: 8/10 | 🔒 Paywalled
Topics: novel_therapeutics, early_cancer_detection
DOI: 10.1016/j.annonc.2026.10.096
Design: Phase 3 RCT (final analysis) | Model: human | Maturity: mature
Score breakdown: novelty=2/3, relevance=2/3, design_quality=2/2, population_need=2/2

Key finding: Perioperative nivolumab improved pCR (39.1% vs 29.6%) but did NOT significantly improve event-free survival (HR 0.94, P=0.67) in resectable MIBC at 54.5 months median follow-up; ctDNA positivity and persistence were strongly prognostic for EFS and OS.

Summary: The Phase 3 ENERGIZE trial (n=653) compared perioperative nivolumab plus neoadjuvant gemcitabine-cisplatin versus gemcitabine-cisplatin alone in resectable muscle-invasive bladder cancer; at median 54.5 months follow-up, pathological complete response improved with nivolumab (39.1% vs 29.6%), but the co-primary endpoint of event-free survival was not significantly improved (HR 0.94, P=0.67). Exploratory ctDNA analysis confirmed baseline positivity and cycle-4 persistence as strongly prognostic biomarkers for EFS and OS, providing clinically actionable biomarker findings alongside the negative Phase 3 result.

Triage reason: Final Phase 3 results from a high-profile Ann Oncol trial reporting a negative EFS primary endpoint despite improved pCR with perioperative nivolumab in MIBC, plus novel ctDNA prognostic data; important null finding with direct implications for standard-of-care and biomarker-stratified trial design.

Confidence: high
Authors: Sonpavde G, van der Heijden MS, Gupta S, Galsky MD, Steinberg G, Gschwend JE...

🟡 STANDARD PRIORITY (9 articles)

1. Frontline Bruton tyrosine kinase inhibitors are associated with improved response and PFS in primary CNS lymphoma

PMID: 42913449 | Journal: Blood Adv | Date: 2026-10-23 | Score: 7/10 | 🔓 Open
Topics: hematologic_malignancies
DOI: 10.1182/bloodadvances.2026020093
Design: Retrospective cohort with IPTW adjustment | Model: human | Maturity: developing
Score breakdown: novelty=2/3, relevance=2/3, design_quality=1/2, population_need=2/2

Key finding: BTKi-based frontline therapy in 85 newly diagnosed PCNSL patients was associated with improved PFS (HR 0.57, 95% CI 0.32-1.00, P=0.048) and higher complete response rates (OR 5.50, P<0.001) vs conventional HD-MTX immunochemotherapy after IPTW-balanced comparison.

Summary: This retrospective study of 131 newly diagnosed primary CNS lymphoma patients compared frontline BTK inhibitor-based therapy (n=85) versus conventional high-dose methotrexate immunochemotherapy (n=46) using multiple imputation and inverse probability of treatment weighting to adjust for baseline differences. BTKi-based therapy was associated with improved PFS (HR 0.57, P=0.048) and higher complete response rates (OR 5.50, P<0.001), though OS differences were not statistically significant, reflecting residual confounding inherent to retrospective design.

Triage reason: Well-adjusted retrospective Blood Advances study from Sun Yat-sen supporting BTKi as frontline PCNSL therapy; relevant to the growing evidence base for BTK inhibition in CNS lymphoma and PCNSL treatment algorithm refinement.

Confidence: high
Authors: Wang X, Bai B, Yu S, Wen L, Shi X, Huang H

2. Acute Erythroid Leukemia Associated With Myeloid Neoplasms: Clinicopathologic Features and Evidence of Clonal Continuity

PMID: 42918306 | Journal: Mod Pathol | Date: 2026-10-23 | Score: 7/10 | 🔒 Paywalled
Topics: hematologic_malignancies
DOI: 10.1016/j.modpat.2026.101107
Design: Retrospective multi-institutional cohort | Model: human | Maturity: developing
Score breakdown: novelty=2/3, relevance=3/3, design_quality=1/2, population_need=1/2

Key finding: In 116 AEL cases arising from myeloid neoplasms (68 MDS, 33 MPN), 100% of 58 cases with longitudinal data shared >=1 genetic aberration between precursor MN and AEL, confirming clonal continuity; both MDS- and MPN-transformed AEL converge on complex karyotype/TP53 mutations with dismal OS of ~1.4-1.5 months.

Summary: Through multi-institutional collaboration characterizing 116 cases of acute erythroid leukemia (AEL) arising from myeloid neoplasms (predominantly MDS 59% and MPN 28%), researchers confirmed direct clonal continuity in 100% of 58 cases with longitudinal molecular data. MDS-transformed AEL showed faster progression (7.6 vs 82.4 months), higher initial TP53 mutations (98% vs 11%), and complex karyotype rates (76% vs 8%), while both groups ultimately converged on adverse genomic landscapes with dismal median OS of approximately 1.4-1.5 months.

Triage reason: Largest multi-institutional AEL cohort to date (n=116) providing definitive clonal continuity evidence and detailed molecular pathway characterization for MDS-vs MPN-derived transformation; relevant to AEL diagnostics, prognosis, and understanding leukemic evolution.

Confidence: high
Authors: Fitzpatrick MJ, Yuan J, Akuma DC, Allbee AW, Bledsoe JR, Capa I...

3. Nivolumab plus relatlimab with platinum-doublet chemotherapy versus nivolumab with platinum-doublet chemotherapy in stage IV or recurrent non-small cell lung cancer: clinical, translational, and patient-reported outcomes results from the phase II RELATIVITY-104 study

PMID: 42918419 | Journal: Ann Oncol | Date: 2026-10-23 | Score: 7/10 | 🔒 Paywalled
Topics: novel_therapeutics
DOI: 10.1016/j.annonc.2026.10.103
Design: Phase 2 RCT | Model: human | Maturity: developing
Score breakdown: novelty=2/3, relevance=2/3, design_quality=2/2, population_need=1/2

Key finding: RELATIVITY-104 Part 2 did not meet its primary ORR endpoint (51.3% vs 45.0%) for nivolumab+relatlimab+chemotherapy vs nivolumab+chemotherapy in NSCLC, but showed OS HR 0.60 and ORR 58.0% vs 39.6% in the PD-L1>=1% nonsquamous subgroup, supporting Phase 3 RELATIVITY-1093.

Summary: Part 2 of RELATIVITY-104, the first randomized Phase II study to evaluate dual PD-1/LAG-3 blockade (nivolumab plus relatlimab) added to platinum-doublet chemotherapy versus nivolumab plus chemotherapy alone in stage IV/recurrent NSCLC, did not meet its primary ORR endpoint in the all-randomized population (51.3% vs 45.0%). Clinically meaningful benefit trends in patients with PD-L1 >=1% nonsquamous histology (ORR 58.0% vs 39.6%; OS HR 0.60) provide hypothesis-generating data supporting the ongoing Phase 3 RELATIVITY-1093 investigation in this enriched subgroup.

Triage reason: Phase 2 Ann Oncol RCT providing null primary but positive subgroup signal data on LAG-3+PD-1 dual blockade in NSCLC; informs biomarker-selected trial design for nivolumab+relatlimab and identifies PD-L1>=1% nonsquamous as a potentially responsive population.

Confidence: high
Authors: Girard N, Burotto M, Paz-Ares LG, Schenker M, Lingua A, Orlandi F...

4. Capivasertib plus abiraterone in PTEN-deficient de novo metastatic hormone-sensitive prostate cancer: updated survival analysis from CAPItello-281

PMID: 42918424 | Journal: Ann Oncol | Date: 2026-10-23 | Score: 7/10 | 🔒 Paywalled
Topics: precision_oncology, rare_diseases_high_unmet_need
DOI: 10.1016/j.annonc.2026.10.097
Design: Phase 3 RCT (updated survival analysis) | Model: human | Maturity: developing
Score breakdown: novelty=2/3, relevance=2/3, design_quality=2/2, population_need=1/2

Key finding: Updated survival analysis from CAPItello-281 evaluates capivasertib (AKT inhibitor) plus abiraterone in PTEN-deficient de novo metastatic hormone-sensitive prostate cancer, targeting PI3K/AKT pathway in a poor-prognosis genomically defined subgroup.

Summary: CAPItello-281 is a randomized trial evaluating capivasertib, an oral pan-AKT inhibitor, combined with abiraterone in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer—a biomarker-selected population with inferior outcomes to PTEN-intact disease. This updated survival analysis in Ann Oncol reports long-term efficacy data on AKT pathway inhibition as a precision oncology strategy, with full results available in the publication.

Triage reason: Updated survival data from a Phase 3 Ann Oncol trial on a precision AKT inhibitor+abiraterone combination in PTEN-deficient prostate cancer; relevant to biomarker-guided treatment selection in precision oncology and the growing portfolio of PI3K/AKT-targeted agents.

Confidence: medium
Authors: Fizazi K, Clarke NW, De Santis M, Uemura H, Fay AP, Karadurmus N...

5. 12-month weight-loss trajectories and predictors of response to tirzepatide under individualized dosing: A multicenter real-world study

PMID: 42908672 | Journal: Obes Pillars | Date: 2026-10-12 | Score: 6/10 | 🔓 Open
Topics: cardiovascular_metabolic
DOI: 10.1016/j.obpill.2026.100344 PMC: PMC13683030
Design: Retrospective real-world multicenter observational | Model: human | Maturity: developing
Score breakdown: novelty=1/3, relevance=2/3, design_quality=1/2, population_need=2/2

Key finding: In 249 self-funded Greek patients on individualized tirzepatide, 68.3% remained on treatment at 12 months with mean 19.9% weight loss; 50% achieved >=20% loss, and 6-month response predicted 12-month >=20% loss (OR 1.34/percentage point, AUC 0.760).

Summary: In a multicenter retrospective real-world study of 249 adults with obesity treated with tirzepatide across 13 Greek obesity practices under fully self-funded, individualized dosing conditions, 68.3% remained on treatment at 12 months with a mean weight loss of 19.9% +/-8.6%. Six-month weight-loss response was associated with achieving >=20% cumulative weight loss at 12 months (adjusted OR 1.34 per additional percentage point, P<0.001, AUC 0.760), providing real-world persistence and dose-response trajectory data for this dual GIP/GLP-1 co-agonist.

Triage reason: Real-world 12-month multicenter tirzepatide data from a self-funded cohort provides ecological validity; early-response prediction rule (6-month AUC 0.76) is clinically useful, though limited by retrospective design, COI (Lilly relationships), and Greece-specific practice context.

Confidence: high
Authors: Angelopoulos N, Fousteris E, Zianni D, Androulakis I, Paparodis R, Florakis D...

6. Development and Evaluation of a Two-Stage Machine Learning Multivariable Model to Support Clinical Decision-Making in Thrombophilia Management

PMID: 42913722 | Journal: Thromb Haemost | Date: 2026-10-22 | Score: 6/10 | 🔒 Paywalled
Topics: ai_ml_clinical_diagnostics
DOI: 10.1055/a-2979-5588
Design: Retrospective single-center ML model development | Model: human | Maturity: developing
Score breakdown: novelty=2/3, relevance=2/3, design_quality=1/2, population_need=1/2

Key finding: A two-stage XGBoost ML model trained on 496 thrombophilia patients achieved 91.9% macro-averaged sensitivity when adjacent-class predictions accepted, with antiphospholipid antibody status as the most influential feature; physician concordance was 79.6%, though external validation is needed.

Summary: A two-stage machine learning model (XGBClassifier plus ordinal-specific XGBOrdinalV2) was trained on clinical and laboratory data from 496 patients undergoing complete thrombophilia work-up at University Hospital Bonn (2019-2024) to predict thrombophilia risk category and anticoagulation recommendation. Exact-class sensitivity was 58% for diagnosis, improving to 91.9% when adjacent-class predictions were accepted; antiphospholipid antibody status, age at first thrombosis, and unprovoked thrombosis were the most influential features, with 79.6% concordance with physician decisions.

Triage reason: Single-center ML model for thrombophilia management with reasonable physician concordance; limited by retrospective single-site design and need for external validation, but demonstrates ML feasibility in a complex hematology clinical decision task.

Confidence: high
Authors: McRae HL, Kahl F, Kapsecker M, Ruhl H, Jonas SM, Potzsch B

7. Sintilimab plus eribulin and carboplatin in patients with metastatic triple-negative breast cancer (SECURE): a phase II, multicenter trial

PMID: 42919625 | Journal: J Immunother Cancer | Date: 2026-10-23 | Score: 6/10 | 🔓 Open
Topics: novel_therapeutics, precision_oncology
DOI: 10.1136/jitc-2026-016269
Design: Phase 2 multicenter trial | Model: human | Maturity: developing
Score breakdown: novelty=1/3, relevance=2/3, design_quality=1/2, population_need=2/2

Key finding: SECURE evaluated the triplet combination of sintilimab (PD-1 inhibitor), eribulin, and carboplatin as a novel chemo-immunotherapy regimen in metastatic triple-negative breast cancer in a multicenter Phase 2 setting.

Summary: The SECURE trial was a Phase II multicenter study evaluating sintilimab (a PD-1 checkpoint inhibitor) combined with eribulin and carboplatin as a novel chemotherapy-immunotherapy triplet in patients with metastatic triple-negative breast cancer. Full efficacy, safety, and biomarker data are reported in this JITC open-access publication; the PubMed abstract was not yet populated at time of indexing, and complete results require full-text access.

Triage reason: Phase 2 multicenter JITC trial of a novel PD-1 plus chemotherapy doublet in metastatic TNBC—a high-unmet-need indication; scored conservatively as title-only at indexing, warrants review upon abstract availability for full scoring.

Confidence: low
Authors: Ni M, Zhou L, Zhang L, Su Y, Shi H, Chen M...

8. Molecular filler-enhanced DNA nanomachines enable one-step multiplex quantification of ctDNA for mutation analysis and metastasis-associated assessment

PMID: 42919761 | Journal: Sci Bull (Beijing) | Date: 2026-10-12 | Score: 6/10 | 🔒 Paywalled
Topics: early_cancer_detection
DOI: 10.1016/j.scib.2026.10.018
Design: Methods development / analytical validation | Model: human | Maturity: emerging
Score breakdown: novelty=2/3, relevance=2/3, design_quality=1/2, population_need=1/2

Key finding: Methylene blue molecular filler-enhanced DNA nanomachines enable simultaneous amplification-free electrochemical detection of EGFR L858R and T790M ctDNA mutations at attomolar LOD (5.2 and 6.0 amol/L) with AUC 0.96 vs qPCR, and show preliminary metastasis-associated signal differences.

Summary: A homogeneous electrochemical platform using metal-ion-mediated DNA self-assembly enhanced by methylene blue molecular fillers enabled simultaneous, amplification-free detection of dual ctDNA biomarkers, achieving 100-fold sensitivity enhancement and 2.5-fold SNR improvement over unfilled controls. Applied to EGFR L858R and T790M mutations in NSCLC with AUCs of 0.96 versus qPCR and attomolar detection limits, the platform also demonstrated applicability to BRAF V600E in thyroid cancer and preliminary differences in ctDNA signals between metastatic and non-metastatic cases.

Triage reason: Novel DNA nanomachine ctDNA detection platform from West China Hospital with strong analytical performance (attomolar LOD, AUC 0.96) and multiplexing capability; promising early-stage technology though limited by small NSCLC cohort and need for prospective clinical validation.

Confidence: high
Authors: Wang Y, Yang H, Li J, Miao Q, Luo H, Lin F...

9. Adverse impact of deletion of the chromosome 6 on clinical outcomes after allogeneic hematopoietic transplantation

PMID: 42913459 | Journal: Blood Adv | Date: 2026-10-23 | Score: 5/10 | 🔓 Open
Topics: hematologic_malignancies
DOI: 10.1182/bloodadvances.2026021320
Design: Registry analysis | Model: epidemiological | Maturity: developing
Score breakdown: novelty=1/3, relevance=2/3, design_quality=1/2, population_need=1/2

Key finding: Chromosome 6p deletion (del6p) at hematological malignancy diagnosis was independently associated with increased allo-HCT relapse risk (HR 1.30, P=0.036), with the effect more pronounced in HLA-mismatched settings, suggesting del6p attenuates graft-versus-leukemia effect through HLA gene loss.

Summary: Using a Japanese national hematopoietic cell transplantation registry, investigators assessed the impact of chromosome 6 short arm deletion (del6p) at hematological malignancy diagnosis on allo-HCT outcomes across a large cohort. Del6p was associated with significantly higher 2-year relapse incidence (48.3% vs 25.7%) and was an independent relapse risk factor in multivariate analysis (HR 1.30, P=0.036), particularly in HLA-mismatched recipients, consistent with del6p-mediated attenuation of graft-versus-leukemia effect through HLA locus loss.

Triage reason: Japanese national registry analysis identifying del6p as an independent allo-HCT relapse risk factor via putative HLA-mediated GVL attenuation; hypothesis-generating for cytogenetic risk stratification in allo-HCT patient selection and conditioning intensity.

Confidence: high
Authors: Tamaki M, Zaimoku Y, Kawamura S, Fukushima K, Yanagisawa R, Hirayama M...

⚪ LOW PRIORITY (5 articles)

1. Deep learning-based identification of Plasmodium vivax and Plasmodium falciparum species and life-cycle stages from thin blood smear images

PMID: 42910861 | Journal: J Appl Microbiol | Date: 2026-10-22 | Score: 4/10 | 🔒 Paywalled
Topics: cbc_diagnostics_ml_hematology
DOI: 10.1093/jambio/lxag261
Design: Proof-of-concept deep learning model | Model: human | Maturity: emerging
Score breakdown: novelty=1/3, relevance=1/3, design_quality=1/2, population_need=1/2

Key finding: YOLOv8n trained on 16,675 annotated blood cell images from 35 malaria-positive patients achieved mAP@0.5 of 0.673 and 99% accuracy distinguishing infected vs uninfected cells, with F1>0.90 for 8/11 Plasmodium life-cycle stage classes.

Summary: A YOLOv8n deep learning framework was trained on 16,675 annotated peripheral blood cell images from 35 malaria-confirmed patients to classify P. vivax and P. falciparum across 11 life-cycle stage classes, achieving an overall mAP@0.5 of 0.673 and 99% accuracy for infected vs uninfected cell discrimination. The proof-of-concept study demonstrated high accuracy for WBC (98.1%) and platelet (99.3%) detection alongside parasite identification, though performance varied across less common life-cycle stages.

Triage reason: Proof-of-concept DL malaria blood smear classifier; limited by very small sample (n=35), same-slide hold-out evaluation, and moderate mAP on uncommon parasite stages—relevant to T2 CBC/ML hematology but primarily a global health DL tool at early development stage.

Confidence: high
Authors: Kaura T, Kumari K, Garg N, Grover GS, Mewara A

2. Arid1a and Arid1b maintain B cell lineage fidelity and constrain myeloid transformation in mice

PMID: 42918388 | Journal: Exp Hematol | Date: 2026-10-23 | Score: 4/10 | 🔒 Paywalled
Topics: hematologic_malignancies
DOI: 10.1016/j.exphem.2026.105956
Design: Preclinical (mouse conditional knockout) | Model: animal | Maturity: emerging
Score breakdown: novelty=2/3, relevance=2/3, design_quality=0/2, population_need=0/2

Key finding: Combined CD19-Cre-mediated Arid1a/Arid1b deletion in mice caused a paradoxical lethal transplantable myeloid leukemia rather than B-cell malignancy, mediated through MPP3 expansion and aberrant erythroid/megakaryocyte-erythroid transcriptional activation in multipotent progenitors.

Summary: Using CD19-Cre-mediated conditional deletion, combined loss of Arid1a and Arid1b—canonical BAF complex subunits recurrently mutated in B-cell malignancies—caused B-cell differentiation failure and paradoxically resulted in a lethal, transplantable myeloid leukemia. CD19-Cre lineage tracing identified BAF complex activity in multipotent progenitors, where combined deletion drove MPP3 expansion and aberrant erythroid/megakaryocyte-erythroid gene programs, revealing BAF complexes as essential guardians of hematopoietic lineage fidelity that constrain malignant transformation.

Triage reason: Mouse model study revealing a surprising myeloid transformation phenotype from B-cell-targeted BAF complex deletion, mechanistically interesting for leukemogenesis but currently limited to animal models without direct human translation evidence.

Confidence: high
Authors: Lin PN, Zimmerman SM, Park J, Kang YA, Souroullas GP

3. Risk Factors for Admission to the Intensive Care Unit and Mortality in Allogeneic Hematopoietic Cell Transplant Recipients with Acute Myeloid Leukemia

PMID: 42918577 | Journal: Transplant Cell Ther | Date: 2026-10-23 | Score: 4/10 | 🔒 Paywalled
Topics: hematologic_malignancies
DOI: 10.1016/j.jtct.2026.10.037
Design: Retrospective single-institution cohort | Model: human | Maturity: developing
Score breakdown: novelty=1/3, relevance=2/3, design_quality=1/2, population_need=0/2

Key finding: Among 1,265 AML/MDS allo-HCT recipients (2006-2023), ICU admission occurred in 9.2% by day +100; HCT-comorbidity index, TRM score, and HLA-mismatched donor were independent ICU risk factors; 43% of ICU patients died within 100 days.

Summary: A retrospective analysis of 1,265 adults with AML/MDS undergoing allogeneic HCT at Fred Hutchinson Cancer Center (2006-2023) found a 9.2% cumulative incidence of ICU admission by day +100, with HCT-comorbidity index, TRM score, and HLA-mismatched donors independently associated with ICU admission. Within 100 days of ICU admission, 43% of patients died, with poor performance status, higher TRM score, and secondary AML independently associated with ICU mortality.

Triage reason: Single-institution retrospective cohort providing ICU risk factor characterization in AML allo-HCT; useful for pre-transplant counseling and preventive strategy testing but limited by single-center design and relatively standard risk factors identified.

Confidence: high
Authors: Orvain C, Othus M, Halpern AB, Basom RS, Davis C, Sandmaier BM...

4. Implementing polygenic risk scores for breast cancer prevention: protocol for a feasibility study in a real-world clinical setting

PMID: 42919576 | Journal: BMJ Open | Date: 2026-10-23 | Score: 4/10 | 🔓 Open
Topics: precision_oncology
DOI: 10.1136/bmjopen-2026-121783
Design: Study protocol (feasibility) | Model: human | Maturity: emerging
Score breakdown: novelty=1/3, relevance=1/3, design_quality=0/2, population_need=2/2

Key finding: Protocol for a real-world feasibility study assessing integration of polygenic risk scores for breast cancer prevention into clinical practice at an Italian tertiary academic center.

Summary: This is a BMJ Open study protocol paper describing a feasibility study for implementing polygenic risk scores (PRS) for breast cancer prevention in a real-world Italian clinical setting at Fondazione Policlinico Universitario Gemelli IRCCS. The protocol details the methodology for integrating PRS into breast cancer prevention pathways, patient selection, and clinical workflow assessment; no study results are available, as this is a study design publication.

Triage reason: Protocol-only paper describing PRS implementation feasibility for breast cancer prevention; scored conservatively as no results are available at indexing, relevant to precision oncology policy and genomic prevention but lacking evidence to score higher.

Confidence: medium
Authors: Farina S, Causio FA, Risuleo PE, Verduchi A, Pascucci E, Sabatelli A...

5. From DNA damage to systemic immunity: Interaction networks in radio-immunotherapy

PMID: 42908903 | Journal: Cell Insight | Date: 2026-09-12 | Score: 3/10 | 🔓 Open
Topics: novel_therapeutics
DOI: 10.1016/j.cellin.2026.100360 PMC: PMC13683422
Design: Review | Model: human | Maturity: mature
Score breakdown: novelty=1/3, relevance=1/3, design_quality=0/2, population_need=1/2

Key finding: Comprehensive narrative review synthesizing molecular interaction networks (protein-protein, protein-DNA, gene-drug, protein-drug) governing radio-immunotherapy synergy, covering cGAS-STING sensing, abscopal effects, immunogenic cell death, and clinical evidence across tumor types.

Summary: This single-author narrative review examines the molecular interaction networks governing radiotherapy and immune checkpoint inhibitor synergy, including cGAS-STING-mediated nucleic acid sensing, the abscopal and RadScopal effects, and immunogenic cell death mechanisms. The review also covers clinical evidence for combined radio-immunotherapy across tumor types and discusses future challenges including optimal treatment sequencing, particle choice, the 'badscopal' effect, and biomarker-guided patient selection.

Triage reason: Single-author narrative review in a secondary open-access journal; comprehensive but does not present new data or systematic analysis; included for T6 novel therapeutics topic coverage at LOW priority.

Confidence: high
Authors: Huang R

Per-Topic Coverage

Search Log