PubMed Daily Triage Digest — 2026-08-13
Run ID: 2026-08-13-attempt3-20260813T094813Z NCBI window: CRDT 2026-08-12 → 2026-08-13 | Attempt: 3 of 3 (schema repair) Screened: 133 candidates across 9 watchlist topics + sentinel Emitted: 26 articles — 10 HIGH | 13 STANDARD | 3 LOW Run status: SUCCESS
🔴🟠 HIGH PRIORITY (8+) — Best Finds by Topic
Precision Oncology / Genomics
[PMID 42586783] Chen C, Zhu J et al. — J Med Genet (2026-08-12) Actionable genotypes beyond the coding sequence and their association with lifespan — UK Biobank (N=490,086) Score: 9/10 🟢 Near-term implementable | Abstract only | Prospective cohort genomics | Validated
Coding ACMG actionable genotypes (3.4% prevalence) increase all-cause mortality HR 1.42 (F) and 1.31 (M). Functionally verified promoter variants with downregulating activity in cancer genes additionally predict mortality (HR ~1.13) via saturation mutagenesis + MPRA — first large-scale non-coding actionable variant mortality demonstration. Reshapes secondary genomic findings policy. doi:10.1136/jmg-2026-111659
AI/ML in Clinical Diagnostics and Imaging
[PMID 42585992] Song B, Maurya H et al. — Eur J Cancer (2026-08-07) Stromal-immune computational pathology signature for prognosis and ICI response in urothelial carcinoma — 5 cohorts, N=884 Score: 9/10 🟢 Near-term implementable | Abstract only | Multicenter retrospective | Validated
Automated H&E-based TLS density + tumor-stroma ratio (TSR) integrated signature predicts PFS across 5 independent UC cohorts and identifies ICI responders (AUC 0.745). Outperforms individual biomarkers (C-index 0.65–0.69); pathologist-independent ICI selection biomarker for bladder/urothelial cancer. doi:10.1016/j.ejca.2026.116979
Early Cancer Detection (Liquid Biopsy / ctDNA / cfDNA)
[PMID 42585615] Beijert IJ, Wever BMM et al. — JCO Precis Oncol (2026-08-12) iSECURE: integrated methylation + copy number cfDNA for noninvasive bladder cancer detection in home-collected urine — AUC 0.94 Score: 9/10 🔴 Early cancer detection | Abstract only | Prospective diagnostic cohort | Validated
Single urine cfDNA library for both SCNA profiling and 3-gene methylation (GALR1/HAND2/NRN1). AUC 0.94, 88% sensitivity, 94% specificity; LOOCV in 89 subjects (30 primary BC, 28 recurrent, 31 hematuria controls). Home-collected urine; potential cystoscopy replacement for low-risk surveillance. doi:10.1200/PO-25-00882
[PMID 42584731] Xu Y, Wang S et al. (Geneseeq) — Mol Biomed (2026-08-12) 🟢 Open Fragmentia-AI WGS: pan-cancer cfDNA detection from ULP-WGS via transformer MIL — 17 cancer types, AUC 0.930 Score: 8/10 🔴 Early cancer detection | PMC full text | Retrospective multicenter | Validated
Sequential fine-tuning across TF strata improved low-TF AUC 35.6%. External cross-platform validation AUC 0.929 (sensitivity 0.78, specificity 0.92). Model-negative status associated with improved PFS in NSCLC chemoimmunotherapy (HR 0.49, 95% CI 0.29–0.82). Industry authorship (Geneseeq) warrants independent replication. doi:10.1186/s43556-026-00538-w
Hematologic Malignancies (AML, MDS, CLL, MPN, Lymphoma)
[PMID 42585304] Mapperley C, Georges E et al. — Sci Adv (2026-08-14) 🟢 Open RNA terminal uridylyl transferases TUT4/7 are druggable AML vulnerabilities, sparing normal hematopoiesis Score: 9/10 🟠 Novel treatment | PMC full text | Mechanistic preclinical | Exploratory
TUT4/7 genetic deletion suppresses AML growth in mouse models via mevalonate/cholesterol pathway; synergizes with venetoclax in primary patient samples. Normal hematopoiesis and full lifespan preserved in Tut4/7-deficient mice. Redona Therapeutics co-authorship signals clinical program. doi:10.1126/sciadv.aec3399
[PMID 42585696] Song C, Liu W et al. — Drug Resist Updat (2026-08-12) ZBED6-driven nucleotide metabolic reprogramming as anti-PD1 resistance mechanism in NK/T-cell lymphoma Score: 8/10 🟠 Novel treatment | Abstract only | Mechanistic preclinical | Exploratory
ZBED6 downregulation enables NKTL cells to scavenge thymidine via SLC29A1/E2F1-RRM2/DPYD axis, creating immunosuppressive TME. Validated by 280-day 5-round resistance induction with humanized PBMC reconstitution + transcriptomics/proteomics/metabolomics + clinical NKTL samples. doi:10.1016/j.drup.2026.101466
Novel Therapeutics: Immunotherapy / CAR-T / Targeted Therapy
[PMID 42586608] Wang Y, Peng C et al. — J Immunother Cancer (2026-08-12) 🟢 Open PGE2-mediated NK cell reprogramming drives acquired PD-1 resistance in lung adenocarcinoma — CRISPR screen identifies COX-2 Score: 8/10 🟠 Novel treatment | PMC full text | Mechanistic preclinical | Exploratory
In vivo genome-wide CRISPR screen identified Ptgs2 as dominant acquired PD-1 resistance driver. PGE2 signals via EP2/EP4→cAMP→CREM to suppress NK-cell cytotoxicity. COX-2 inhibitor celecoxib restored NK function and overcame resistance in vivo. Immediately actionable for NSCLC celecoxib + anti-PD-1 combination trial design. doi:10.1136/jitc-2025-014673
[PMID 42586609] Sirini C, Balestrieri C et al. (San Raffaele) — J Immunother Cancer (2026-08-12) 🟢 Open N-glycans on non-malignant TME cells dampen CAR-T function in colorectal and pancreatic cancer — MGAT5 actionable target Score: 8/10 🟠 Novel treatment | PMC full text | Mechanistic preclinical | Exploratory
N-glycan branching on M2 macrophages and hepatic stellate cells limits CAR-T in CRC/PDAC liver mets. Humanized mouse + scRNA-seq: MGAT5 disruption in TME (not tumor) depletes pro-tumor IL1β+ macrophages and restores CAR-T activity. Novel TME glycosylation mechanism; MGAT5 inhibitors tractable. doi:10.1136/jitc-2026-015099
Cardiovascular-Metabolic (GLP-1 / SGLT2 / Cardiometabolic Risk)
[PMID 42586506] Kanbay M, Mizrak B et al. — Diabetes Res Clin Pract (2026-08-12) SGLT2 inhibitors in ADPKD: first systematic review/meta-analysis — 6 studies, N=451 — inconclusive but signals trial urgency Score: 8/10 🟡 Underserved population | Abstract only | Systematic review + meta-analysis | Exploratory
First PRISMA-registered meta-analysis of SGLT2i in ADPKD (excluded from pivotal trials). Modest eGFR attenuation vs. historical slope (MD 0.65 mL/min/1.73m²/yr, p=0.04) but no significant advantage over active comparators, no kidney volume reduction. Urgently calls for dedicated ADPKD RCTs. doi:10.1016/j.diabres.2026.113496
Rare Diseases with High Unmet Need
[PMID 42585307] Zhao W, Hu X et al. — Sci Adv (2026-08-14) 🟢 Open Mito-TEMPO improves survival in NPC1-knockout zebrafish via Sod2-mediated mitophagy — Niemann-Pick type C therapeutic target Score: 8/10 🟠 Novel treatment | PMC full text | Mechanistic preclinical (zebrafish) | Exploratory
Mito-TEMPO (mitochondria-targeted antioxidant) extends survival in npc1−/− zebrafish by reducing mitochondrial oxidative stress and enhancing mitophagy via SOD2 activation. NPC1/Niemann-Pick type C has no disease-modifying treatment; mitochondrial dysfunction is a druggable mechanism. Concept translatable to mammalian NPC1 models. doi:10.1126/sciadv.aee0509
Aging / Longevity / Population Health
No HIGH-priority articles this run (best score: 7/10). See STANDARD section below.
🟢⚪ STANDARD (4–7) — Top by Topic
| PMID | Title (abbreviated) | Topic | Score | Priority Flag | Journal |
|---|---|---|---|---|---|
| 42585095 | Aging-associated GATA4 in articular cartilage impairs chondrocyte regeneration — OA mechanism | T8 Aging | 7 | ⚪ Promising prelim. | eLife 🟢 |
| 42585000 | miR-34a–KLF2–CXCR4/CXCL12 axis drives AMD neovascularization — non-VEGF target | T8 Aging | 7 | ⚪ Promising prelim. | PNAS |
| 42586237 | Clone-by-clone spatial proteomics therapy guidance in luminal breast cancer (tumoroids) | T5 Precision Onc | 7 | ⚪ Promising prelim. | Mol Cell Proteomics |
| 42586900 | AZA-VEN + G-CSF in real-world AML — G-CSF OS benefit in CR/CRi (10.1 vs 20.3 mo, p=0.001) | T1 Heme Malig | 6 | 🟢 Near-term impl. | Clin Lymphoma Myeloma Leuk |
| 42585617 | NLP+EHR AML readmission/mortality risk — AUC 0.67→0.74 with clinical notes | T1/T4 | 6 | 🟢 Near-term impl. | JCO Clin Cancer Inform |
| 42586458 | Obesity-driven HFpEF: SGLT2i + semaglutide/tirzepatide treatment framework | T7 CardioMet | 6 | 🟢 Near-term impl. | Curr Probl Cardiol |
| 42586224 | Claudin18.2 molecular imaging for precision oncology — target accessibility beyond IHC | T5 Precision Onc | 6 | ⚪ Promising prelim. | Pharmacol Res |
| 42586156 | ML for thalassemia detection — critical review, CBC/ML pipeline gaps and recommendations | T2 CBC-ML | 6 | 🟡 Underserved pop. | Prog Biomed Eng 🟢 |
| 42584390 | Fabry disease cardiac remodeling trajectory by renal stage — East Asian cohort | T9 Rare Disease | 6 | 🟡 Underserved pop. | JACC Asia |
| 42586901 | CAR-T geographic/socioeconomic disparities in MM (N=106,593) — drive time + income barriers | T6/T1 | 5 | 🟡 Underserved pop. | Clin Lymphoma Myeloma Leuk |
| 42585667 | TMAO associated with aging, cardiometabolic risk, and brain atrophy in elderly (N=487, MRI) | T8 Aging | 5 | ⚪ Promising prelim. | Aging (Albany NY) 🟢 |
| 42584890 | Retest effects in cognitive aging assessments — RCT methodological implications for AD trials | T8 Aging | 5 | 🟢 Near-term impl. | JAMA Netw Open 🟢 |
| 42584677 | Fabry disease vascular endothelial dysfunction + echo — sex-specific patterns | T9 Rare Disease | 5 | ⚪ Promising prelim. | Clin Res Cardiol |
🔵 LOW (≤3) — Title-Only Records (Archived)
Scored ≤3 per title-only conservative cap; held for record completeness.
| PMID | Title (abbreviated) | Topic | Score | Journal |
|---|---|---|---|---|
| 42586812 | Nano-activators for antigen-independent T cell activation in solid tumors (title only) | T6 Immunotherapy | 3 | Sci Bull (Beijing) |
| 42586811 | In situ NKG2D CAR T/NK cells via tumor-targeted lipoplex (title only) | T6 Immunotherapy | 3 | Sci Bull (Beijing) |
| 42585652 | Gene editing, peroxisomal disorders, rare disease treatments — NEJM commentary (title only) | T9 Rare Disease | 3 | N Engl J Med |
Score capped at 3 for title-only records per v1.3 conservative triage policy. Recommend re-triage when abstract becomes available.
💡 UNSOLICITED FINDS
None. All sentinel scan candidates (10 reviewed) overlapped with watchlist topic captures. No unique high-signal out-of-watchlist articles identified today.
📊 TODAY'S BREAKDOWN
By research category:
- Treatment Innovation: 8 articles
- Diagnostics: 7 articles
- Drug Development: 4 articles
- Early Detection: 2 articles
- Public Health: 1 article
- Genomics/Precision Medicine: 1 article
- Other: 2 articles
- Prevention: 0 articles
- Mental Health: 0 articles
By evidence maturity:
- Exploratory: 20 articles
- Validated: 6 articles (42586783, 42585992, 42585615, 42584731, 42584890; 42585095 reclassified Exploratory per attempt 2 correction)
- Potentially Practice-Changing: 0 articles
By watchlist topic (search hits / reviewed / HIGH / STANDARD / highest score):
| Topic | Search Hits | Reviewed | HIGH | STANDARD | LOW | Highest Score |
|---|---|---|---|---|---|---|
| T1 Hematologic malignancies | 48 | 15 | 2 | 3 | 10 | 9 (42585304) |
| T2 CBC/ML hematology | 1 | 1 | 0 | 1 | 0 | 6 (42586156) |
| T3 Early cancer detection | 33 | 15 | 2 | 0 | 13 | 9 (42585615) |
| T4 AI/ML clinical diagnostics | 35 | 15 | 1 | 1 | 13 | 9 (42585992) |
| T5 Precision oncology/genomics | 63 | 15 | 1 | 2 | 12 | 9 (42586783) |
| T6 Novel therapeutics/immunotherapy | 146 | 15 | 2 | 1 | 12 | 8 (42586609) |
| T7 Cardiovascular-metabolic | 93 | 15 | 1 | 1 | 13 | 8 (42586506) |
| T8 Aging/longevity | 23 | 10 | 0 | 4 | 6 | 7 (42585095) |
| T9 Rare diseases | 29 | 14 | 1 | 2 | 11 | 8 (42585307) |
| Sentinel | 10 | 10 | 0 | 0 | 10 | — |
By source type: peer_reviewed: 26 | preprint: 0
By access level: PMC full text: 9 | Abstract only: 14 | Title only: 3
Topics with zero 8+ articles this run: T2 CBC/ML hematology (best: 6/10), T8 Aging (best: 7/10), Sentinel (no unique finds)
🔧 RUN NOTES
- Attempt 3 schema repair: All concrete validator errors from attempt 2 corrected; no biomedical conclusions changed.
- Fix 1 — search_logs format:
run_metadata.search_logsconverted from object (keyed by topic name) to required array of log objects. All 10 topic entries preserved with same PMID coverage data. - Fix 2 — pipeline_priority for score-7 articles: PMIDs 42586237, 42585095, 42585000 corrected from HIGH to STANDARD. Schema rule: HIGH requires triage_score ≥8 OR flag in [EARLY_CANCER_DETECTION, NOVEL_TREATMENT]. All three have score 7 and flag PROMISING_PRELIMINARY. Moved to STANDARD in digest; topic best_pmid and highest_score unchanged.
- Fix 3 — title-only score cap: PMIDs 42586812, 42586811, 42585652 corrected from triage_score 4 to 3. Schema rule: title-only records cannot exceed triage_score 3. score_breakdown sums adjusted (novelty 2→1 for 42586812/42586811; population_or_unmet_need 2→1 for 42585652). pipeline_priority corrected from STANDARD to LOW (score ≤3).
- Count updates: high_priority_count 13→10; low_count 0→3; standard_count remains 13. Per-topic stats for Precision Oncology (high 2→1), Aging (high 2→0, standard 2→4), Novel Therapeutics (standard 3→1, low 10→12), and Rare Diseases (standard 3→2, low 10→11) updated.
- Salvage limitation: Low-scoring candidate PMIDs (those reviewed but scored <5 and not retained) could not be recovered from the salvage bundle. Search log candidate_pmids arrays contain only retained article PMIDs;
coverage_complete=falsereflects this for topics with uncovered candidates. - Aging/longevity query: humans[MeSH] filter applied to reduce non-human biology noise as documented in watchlist guidance.
- Novel therapeutics topic: High noise (146 hits) from nanocarrier/polymer delivery papers; restricted to immunotherapy mechanism and translational papers.
Generated: 2026-08-13T09:48:13Z | Attempt 3 of 3 (schema repair) | Pending validator promotion to final paths