847
Abstracts scored today
6
Papers simplified (2026)
2
Retractions documented
Papers of the week
Amyloid-beta plaques disrupting synaptic transmission. phd.today original illustration, CC0.
An Alzheimer's Drug That Finally Slows the Clock. By 27%.
Why it matters: Lecanemab is the first drug to show statistically significant slowing of Alzheimer's decline in a large Phase 3 trial. Small effect, real signal.
| Question | Does lecanemab slow clinical decline in early symptomatic Alzheimer's disease? |
| Sample | 1,795 adults with early Alzheimer's (MCI or mild dementia plus confirmed amyloid) randomized 1:1 |
| Method | 18-month double-blind RCT; primary outcome CDR-SB (Clinical Dementia Rating sum of boxes); secondary endpoints amyloid PET, tau PET |
| Finding | Lecanemab reduced CDR-SB decline by 27% vs placebo (1.21 vs 1.66 points; p less than 0.001); amyloid burden fell 59.1 centiloid units vs +2.1 placebo |
| Limitation | ARIA (brain swelling and microbleeds) in 21.5% of treated patients vs 9.5% placebo; 17 serious ARIA cases in treatment arm |
| Next step | Long-term safety data; subgroup analysis in APOE4 carriers who had highest ARIA rates |
Active recall
SELECT trial MACE rates: semaglutide vs placebo in 17,604 adults with obesity. phd.today original, CC0.
The Weight-Loss Shot That Also Cut Heart Attacks by a Fifth
Why it matters: Semaglutide cut major cardiovascular events by 20% in people with obesity but no diabetes, reframing GLP-1 drugs as cardioprotective beyond their metabolic effects.
| Question | Does semaglutide reduce major adverse cardiovascular events (MACE) in overweight or obese adults without diabetes? |
| Sample | 17,604 adults (BMI at least 27, prior cardiovascular disease, no diabetes); randomized 1:1 to semaglutide 2.4mg weekly or placebo |
| Method | SELECT trial: double-blind RCT, median 34-month follow-up; primary endpoint MACE (CV death, non-fatal MI, non-fatal stroke) |
| Finding | Semaglutide reduced first MACE by 20% vs placebo (HR 0.80, 95% CI 0.72 to 0.90; p less than 0.001); mean weight loss 9.4% vs 0.88% placebo |
| Limitation | Most participants were white men; CV benefit mechanism unclear (weight loss vs direct vascular effects vs both) |
| Next step | Mechanistic sub-studies; trials in heart failure with preserved ejection fraction underway |
Active recall
SURMOUNT-1: body-weight change over 72 weeks, tirzepatide vs placebo. phd.today original, CC0.
22% of Body Weight Lost. Tirzepatide Rewrites the Obesity Ceiling.
Why it matters: Tirzepatide (dual GIP and GLP-1 agonist) achieved 22% mean weight loss at the highest dose, surpassing every previous obesity drug and approaching bariatric surgery outcomes.
| Question | Does tirzepatide produce superior weight loss compared to placebo in adults with obesity or overweight? |
| Sample | 2,539 adults with BMI at least 30 (or at least 27 with comorbidity), without type 2 diabetes; randomized to 5mg, 10mg, 15mg weekly or placebo |
| Method | SURMOUNT-1: 72-week double-blind RCT; primary endpoints 5% weight reduction responder rate and mean percent weight change from baseline |
| Finding | Tirzepatide 15mg: mean weight loss 22.5% vs 2.4% placebo; 96% vs 28% achieved at least 5% weight reduction; 57% vs 3% achieved at least 20% weight reduction |
| Limitation | Trial excluded patients with type 2 diabetes; GI side effects (nausea, diarrhea) led to 5% discontinuation in highest-dose arm |
| Next step | SURMOUNT-2 in patients with type 2 diabetes; cardiovascular outcomes trial (SURPASS-CVOT) |
Active recall
CRISPR-Cas9 corrects sickle cell mutation; red cells normalise. phd.today original, CC0.
CRISPR Fixed Their Sickle Cell Disease. It Stayed Fixed.
Why it matters: The first published human trial of CRISPR-Cas9 gene editing for sickle cell disease and beta-thalassemia showed durable correction with no serious adverse events from the edit itself.
| Question | Can CRISPR-Cas9 editing of BCL11A in hematopoietic stem cells safely produce therapeutic levels of fetal hemoglobin in sickle cell disease and beta-thalassemia? |
| Sample | 2 patients: 1 with transfusion-dependent beta-thalassemia, 1 with severe sickle cell disease; single infusion of edited autologous stem cells |
| Method | Ex vivo CRISPR-Cas9 editing of BCL11A enhancer in patient's own HSCs; transplanted after myeloablative conditioning; followed 12+ months |
| Finding | Beta-thalassemia patient: transfusion-free at 15 months; fetal Hb rose to 46% of total. SCD patient: no vaso-occlusive crises at 12 months; fetal Hb 48% of total |
| Limitation | Only 2 patients in this initial report; myeloablative conditioning carries risk; long-term follow-up data still accumulating |
| Next step | Expanded trials; off-the-shelf allogeneic editing approaches; reducing conditioning toxicity |
Active recall
MASH liver fat accumulation before and after resmetirom treatment. phd.today original, CC0.
The First Pill to Actually Reverse Liver Scarring in MASH
Why it matters: Resmetirom (a thyroid hormone receptor-beta agonist) is the first drug approved that both reduces liver fat and reverses fibrosis in metabolic-associated steatohepatitis, a disease with no prior pharmacologic treatment.
| Question | Does resmetirom improve liver histology and reverse fibrosis in patients with MASH and liver fibrosis? |
| Sample | 966 adults with MASH (biopsy-confirmed) and F1B to F3 liver fibrosis; randomized 1:1:1 to resmetirom 80mg, 100mg, or placebo daily |
| Method | REGENERATE trial: 52-week double-blind RCT; co-primary endpoints MASH resolution without fibrosis worsening and at least 1-stage fibrosis improvement |
| Finding | Resmetirom 100mg: 25.9% achieved fibrosis improvement vs 14.2% placebo (p less than 0.001); 29.9% MASH resolution vs 9.7% placebo; liver fat fell 40% by MRI-PDFF |
| Limitation | Trial used histologic endpoints, not hard clinical outcomes (cirrhosis, liver failure); 12-week extension data pending |
| Next step | MAESTRO-NASH OUTCOMES trial: hard clinical endpoints (decompensated cirrhosis, liver-related death) as co-primary |
Active recall
PFS rates at 12 months: pembrolizumab vs chemotherapy in PD-L1-high NSCLC. phd.today original, CC0.
Skip the Chemo: Immunotherapy Alone Doubled Survival in This Lung Cancer
Why it matters: KEYNOTE-024 showed pembrolizumab halved the risk of disease progression or death vs platinum chemotherapy in PD-L1-high non-small-cell lung cancer, establishing immunotherapy as the new first-line standard.
| Question | Does pembrolizumab monotherapy improve progression-free survival vs platinum-based chemotherapy in previously untreated PD-L1-high NSCLC? |
| Sample | 305 adults with stage IV NSCLC, PD-L1 TPS at least 50%, no EGFR or ALK alterations; randomized 1:1 to pembrolizumab 200mg q3w or investigator-choice platinum chemotherapy |
| Method | Open-label RCT; primary endpoint PFS (IRC-assessed); key secondary endpoints OS, ORR, DOR; cross-over allowed at progression |
| Finding | Pembrolizumab: median PFS 10.3 months vs 6.0 months chemo (HR 0.50, 95% CI 0.37 to 0.68; p less than 0.001); 12-month PFS 47.3% vs 28.2%; ORR 44.8% vs 27.8% |
| Limitation | Open-label design; cross-over contaminated OS signal; only 27% of all NSCLC patients are PD-L1 high |
| Next step | KEYNOTE-189 added pembro to chemo for PD-L1-unselected patients; combination now standard in all-comers |
Active recall
Retractions
Duplicated western blot images across 11 papers by the same PI: three journals pull the plug
| Stated reason | Image duplication and manipulation identified by post-publication peer review (PubPeer) |
| ORI involvement | ORI investigation opened |
| Author response | Contested by corresponding author; institutional investigation ongoing |
Overlapping patient records invalidated RCT results: Lancet retracts cardiovascular trial
| Stated reason | Patient records found overlapping across two trial sites; data integrity cannot be confirmed |
| ORI involvement | None |
| Author response | Authors agreed to retraction |
The publishing system
Peer review takes 5 months on average. Most of that time is chasing reviewers, not actually reviewing.
The bottleneck in scientific publishing is not quality control. It is reviewer recruitment. Three studies from 2022 to 2024 put the average time-to-first-decision between 4.2 and 6.8 months, with reviewer recruitment accounting for 55 to 70% of that window.
| Source | Finding |
|---|---|
| Publons Global Review Report | Average 5.1 months time-to-decision across 1,300 journals (2023) |
| eLife editorial analysis | Reviewer recruitment = 58% of pre-decision delay (2022) |
| PLOS ONE internal data | Median 4.2 months; 30% of papers take 8+ months (2024) |