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Browse the failure-mode index

12,240 real negative results, null findings, and replication failures in Medicine. Search the index →

WASTE indexes published research — it does not host or republish full papers. Each entry is a metadata record compiled from open scholarly databases; the abstract is shown in full only where the paper is openly licensed, otherwise a short excerpt under fair use. Classifications are automated and approximate.

Replication FailureOpen accessMedicine

Randomized trial investigating the utility of a liver tissue transcriptional biomarker in identifying adult liver transplant recipients not requiring maintenance immunosuppression

Julien Vionnet, Jorge P. Torres-Yaguana, Rosa Miquel et al. · 2024 · American Journal of Transplantation

The maintenance of stable allograft status in the absence of immunosuppression (IS), known as operational tolerance, can be achieved in a small proportion of liver transplant recipients, but we lack reliable tools to predict its spontaneous development. We conducted a prospective, multicenter, biomarker-strategy design, IS withdrawal clinical trial to determine the utility of a predictive biomarker of operational tolerance. The biomarker test, originally identified in a patient cohort with high operational tolerance prevalence, consisted of a 5-gene transcriptional signature measured in liver

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Negative / Null Result ReportOpen accessMedicine

Risk stratification and scoring systems in upper and lower gastrointestinal bleeding: review of performance and limitations in the emergency department

Fatemeh Mohammadyari, Amirreza Aflak, Mahta ZareDini et al. · 2025 · Frontiers in Medicine

Background: Gastrointestinal bleeding (GIB), which includes both upper GIB (variceal and non-variceal) and lower GIB, represents a significant cause of emergency department referrals. Main body: Given the potential risks of blood transfusion, re-bleeding, and mortality in these patients, it is essential to establish a system for prioritizing critical patients. Several risk stratification scoring systems have been developed based on patients' clinical characteristics and/or endoscopic findings. However, the optimal scoring system for each clinical scenario remains uncertain. Conclusion: In this

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Negative / Null Result ReportOpen accessMedicine

Effects of Dietary Interventions on Cognitive Outcomes

Judith Charbit, Jean‐Sébastien Vidal, Olivier Hanon · 2025 · Nutrients

Cognitive aging is a complex, multifactorial process influenced by genetic, metabolic, and environmental factors. Among modifiable risk factors, nutrition has emerged as a promising target to preserve cognitive function. This review provides a comprehensive overview of the impact of dietary interventions-including specific nutrients and dietary patterns-on cognitive domains (memory, executive function, global cognition) and mental health. Recent findings: multinutrient supplementation, particularly combinations of B vitamins and omega-3 fatty acids, appears beneficial for episodic memory, espe

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Negative / Null Result ReportOpen accessMedicine

Neutrophil-initiated nociceptive ingrowth orchestrates inflammation resolution to potentiate bone regeneration

Xuanyu Qi, Guangzheng YANG, Zeqian Xu et al. · 2026 · Bone Research

Abstract Nociceptive pain is a cardinal feature of traumatic and inflammatory bone diseases. However, whether and how nociceptors actively regulate the immune response during bone regeneration remains unclear. Here, we found that neutrophil-triggered nociceptive ingrowth functioned as negative feedback regulation to inflammation during bone healing. A unique Il4ra + Ccl2 high neutrophil subset drove intense postinjury TRPV1 + nociceptive ingrowth, which in return dissipated inflammation by activating the production of pro-resolving mediator lipoxin A4 (LXA4) in osteoblasts. Mechanistically, os

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Negative / Null Result ReportOpen accessMedicine

Identifying SCS Trial Responders Immediately After Postoperative Programming with ECAP Dose-Controlled Closed-Loop Therapy

Jason E. Pope, Ajay Antony, Erika Petersen et al. · 2024 · Pain and Therapy

INTRODUCTION: Drawbacks of fixed-output spinal cord stimulation (SCS) screening trials may lead to compromised trial outcomes and poor predictability of long-term success. Evoked compound action potential (ECAP) dose-controlled closed-loop…

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Negative / Null Result ReportOpen accessMedicine

Vitamin D and Chronic Disorders: A Review of Metabolic and Cardiovascular Diseases

Ewelina Młynarska, Wiktoria Lisińska, Katarzyna Hossa et al. · 2025 · Pharmaceuticals

Vitamin D, long recognized for its essential role in calcium-phosphate balance and bone health, has increasingly been identified as a pleiotropic regulator of metabolic, cardiovascular, and renal function. Deficiency of vitamin D is widespread worldwide and has been linked to a higher risk of insulin resistance, type 2 diabetes, atherosclerosis, hypertension, and chronic kidney disease. Meta-analyses suggest that each 10 nmol/L (≈4 ng/mL) increase in serum 25-hydroxyvitamin D [25(OH)D] is associated with about a 4% lower risk of type 2 diabetes, whereas other analyses indicate an approximately

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Replication FailureOpen accessMedicine

Transarterial chemoembolization plus atezolizumab and bevacizumab in patients with intermediate hepatocellular carcinoma: a single-arm, phase 2 trial

Kang Wang, Jinkai Feng, Hongming Yu et al. · 2025 · Signal Transduction and Targeted Therapy

Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC), yet its efficacy as a standalone therapy remains suboptimal. This phase 2 trial (ChiCTR2100049829) evaluated the feasibility and safety of TACE combined with atezolizumab and bevacizumab in patients with intermediate-stage HCC. Participants received TACE followed by atezolizumab and bevacizumab until disease progression, unacceptable toxicity, or death. The primary endpoint was objective response rate (ORR) assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1

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Negative / Null Result ReportOpen accessMedicine

Preclinical ex vivo and in vivo models to study immunotherapy agents and their combinations as predictive tools toward the clinic

Iñaki Eguren‐Santamaría, Ignacio Melero, Inmaculada Rodríguez et al. · 2025 · Journal for ImmunoTherapy of Cancer

Almost every successful anticancer treatment has been preceded by preclinical scientific breakthroughs that encouraged clinical development. However, therapeutic strategies showing promising preclinical results often fail to confirm…

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Negative / Null Result ReportOpen accessMedicine

CONCUSS randomised clinical trial of vergence/accommodative therapy for concussion-related symptomatic convergence insufficiency

Tara L. Alvarez, Mitchell Scheiman, Farzin Hajebrahimi et al. · 2025 · British Journal of Sports Medicine

OBJECTIVE: The CONCUSS randomised clinical trial compared the effectiveness of immediate office-based vergence/accommodative therapy with movement (OBVAM) to delayed therapy for the treatment of concussion-related convergence insufficiency…

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Negative / Null Result ReportOpen accessMedicine

Impact of a Symptom Checker App on Patient-Physician Interaction Among Self-Referred Walk-In Patients in the Emergency Department: Multicenter, Parallel-Group, Randomized, Controlled Trial

Malte L Schmieding, Marvin Kopka, Myrto Bolanaki et al. · 2025 · Journal of Medical Internet Research

BACKGROUND: Symptom checker apps (SCAs) are layperson-facing tools that advise on whether and where to seek care, or possible diagnoses. Previous research has primarily focused on evaluating the accuracy, safety, and usability of their recommendations. However, studies examining SCAs' impact on clinical care, including the patient-physician interaction and satisfaction with care, remain scarce. OBJECTIVE: This study aims to evaluate the effects of an SCA on satisfaction with the patient-physician interaction in acute care settings. Additionally, we examined its influence on patients' anxiety a

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Negative / Null Result ReportOpen accessMedicine

Why Is Clozapine Uniquely Effective in Treatment-Resistant Schizophrenia? A Review and Proposal

Robin Murray, Alice Egerton, Yueming Gao et al. · 2025 · Biological Psychiatry

Much is known about the use, benefits, and side-effects, of clozapine in treatment resistant schizophrenia (TRS). However, why clozapine is more effective than other antipsychotics in TRS remains unclear. This paper addresses this question. TRS patients show glutamate abnormalities, and clozapine has widespread effects on glutamate. However, these actions have not been proven different to those of other antipsychotics. Immune dysfunction is also reported in TRS, and clozapine has anti-inflammatory actions, but these have not been correlated with clinical improvement. Currently, there is much i

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Negative / Null Result ReportOpen accessMedicine

Integration of Artificial Intelligence-Enhanced Capsule Endoscopy in Clinical Practice: A Review of Market-Available Tools for Clinical Practice

A. Giordano, Cristina Romero-Mascarell, Begoña González-Suárez et al. · 2025 · Digestive Diseases and Sciences

The integration of artificial intelligence (AI) into capsule endoscopy is transforming gastrointestinal diagnostics by enhancing lesion detection and optimizing reading efficiency. This review focuses on the clinical applications of…

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Negative / Null Result ReportOpen accessMedicine

Amyloid-beta-targeting monoclonal antibodies for people with mild cognitive impairment or mild dementia due to Alzheimer’s disease

Francesco Nonino, Silvia Minozzi, L. Sambati et al. · 2026 · Cochrane Database of Systematic Reviews

RATIONALE: Alzheimer's disease is a neurodegenerative disorder and the most common cause of dementia. Aggregated amyloid-beta protein deposits are implicated in its pathogenesis. Amyloid-beta-targeting monoclonal antibodies (sometimes represented as Aβ-mAbs) are potentially disease-modifying for Alzheimer's disease: through the clearance of amyloid in the brain, they may slow cognitive and functional decline. OBJECTIVES: To assess the clinical benefits and harms of amyloid-beta-targeting monoclonal antibodies aducanumab, bapineuzumab, crenezumab, donanemab, gantenerumab, lecanemab, ponezumab,

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Negative / Null Result ReportOpen accessMedicine

“Regression to the truth”: lessons learned from negative IPF trials

Athina Trachalaki, Anna Lindahl, Simone Petrarulo et al. · 2025 · Breathe

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with limited treatment options. Despite the approval of pirfenidone and nintedanib that slow disease progression, IPF remains a disease with poor survival. Promising therapeutic…

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Negative / Null Result ReportOpen accessMedicine

Comparison of Deep Learning and Clinician Performance for Detecting Referable Glaucoma from Fundus Photographs in a Safety Net Population

Van Nguyen, Sreenidhi Iyengar, Haroon Rasheed et al. · 2025 · Ophthalmology Science

Purpose Develop and test a deep learning (DL) algorithm for detecting referable glaucoma. Design Retrospective cohort study. Participants A total of 6116 patients from the Los Angeles County (LAC) Department of Health Services (DHS) were…

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Negative / Null Result ReportOpen accessMedicine

Natural history of the revised ALS functional rating scale and its association with survival: the PRECISION-ALS Extant Study

Ruben P. A. van Eijk, Daphne N. Weemering, Sarah Opie-Martin et al. · 2025 · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

Objective To characterize the natural history of the revised ALS functional rating scale (ALSFRS-R) over a 24-month period following initial assessment, and to assess its associations with survival.Methods Longitudinal ALSFRS-R…

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Negative / Null Result ReportOpen accessMedicine

Silybin A from Silybum marianum reprograms lipid metabolism to induce a cell fate-dependent class switch from triglycerides to phospholipids

Solveigh C. Koeberle, Maria Thürmer, Fengting Su et al. · 2025 · Theranostics

: Our study deciphers the structural features of silybin contributing to hepatic lipid remodeling and suggests that silymarin/silybin protects the liver in individuals with mild metabolic dysregulation, involving a lipid class switch from triglycerides to phospholipids, whereas it may be less effective in disease states associated with severe metabolic dysregulation.

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Negative / Null Result ReportOpen accessMedicine

Learning with Generative AI: An Empirical Study of Students in Higher Education

Golan Carmi · 2025 · Education Sciences

Generative AI technologies are rapidly permeating higher education as innovative tools that support teaching and learning processes. This study investigates the integration of GenAI tools into academic learning and examines their influence on students’ learning effectiveness, attitudes, and satisfaction. A quantitative survey was administered to 485 college students. The findings indicate that students’ attitudes, satisfaction, and accumulated experience with GenAI constitute the most influential factors in promoting effective learning. Perceived advantages and disadvantages also play a substa

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Failed Experiment ReportOpen accessMedicine

AMP-activated protein kinase-driven lipid droplet dynamics govern melanoma sensitivity to polyunsaturated fatty acid and iron-induced ferroptosis

Sahar Motamedi, Nina Ravoet, Jonas Dehairs et al. · 2025 · Nature Communications

Ferroptosis, a regulated form of cell death driven by lipid peroxidation, holds promise for targeting treatment-resistant cancer cells. Using a panel of melanoma cell lines, we uncover variability in the timing of ferroptosis onset upon…

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Negative / Null Result ReportOpen accessMedicine

Tissue-resident macrophage survival depends on mitochondrial function regulated by SerpinB2 in chronic inflammation

Sathish Babu Vasamsetti, Samreen Sadaf, Mohammad A. Uddin et al. · 2026 · Nature Communications

How cellular metabolism facilitates tissue-resident macrophage maintenance remains elusive. Here we show that visceral adipose tissue (VAT)-resident macrophages, unlike monocyte-derived macrophages, are enriched with mitochondrial-specific antioxidant enzymes restraining inflammation and promoting VAT homeostasis and insulin sensitivity. Additionally, VAT resident macrophages express high levels of plasminogen activator inhibitor type 2, encoded by SerpinB2, which is involved in the blood coagulation cascade. SerpinB2 promotes adipose resident macrophage survival by regulating mitochondrial ox

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Negative / Null Result ReportOpen accessMedicine

Osteoarthritis: molecular pathogenesis and potential therapeutic options

Yi Zhang, Yanqi Han, Ying Sun et al. · 2026 · Signal Transduction and Targeted Therapy

Osteoarthritis (OA) is a debilitating joint disorder that causes chronic pain, inflammation, and detrimental bone alterations. Despite significant advances in understanding OA pathogenesis, current therapeutic strategies remain inadequate in halting disease progression or providing effective pain relief, highlighting unmet clinical needs. Recent insights into OA nociceptive pathways, inflammatory mediators, and organelle dysfunction have revealed promising therapeutic targets. Specifically, OA progression is driven by mitochondrial dysfunction (marked by accumulated damaged mitochondria with e

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Negative / Null Result ReportOpen accessMedicine

Non-invasive temporal interference stimulation of the hippocampus suppresses epileptic biomarkers in patients with Epilepsy: biophysical differences between kilohertz and amplitude modulated stimulation

Florian Missey, Emma Acerbo, Adam S. Dickey et al. · 2025 · Brain stimulation

INTRODUCTION: Medication-refractory focal epilepsy creates a significant clinical challenge, with approximately 30 % of patients deemed ineligible for surgery due to involvement of eloquent cortical regions within the epileptogenic network. For these patients, electrical neuromodulation represents a promising alternative therapy. We investigated the potential of non-invasive temporal interference (TI) electrical stimulation in reducing epileptic biomarkers in patients with mesiotemporal epilepsy (MTLE) MATERIAL AND METHOD: Thirteen patients implanted with stereoelectroencephalography (sEEG) de

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Replication FailureOpen accessMedicine

Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial

Mette Kruse Klausen, Signe Justesen, Julie Niemann Pedersen et al. · 2026 · The Lancet

BACKGROUND: Alcohol use disorder accounts for 5% of deaths worldwide annually, and there is an urgent need for new therapeutic interventions. Preclinical and initial human studies indicate that the GLP-1 receptor agonist semaglutide might reduce alcohol drinking. This study evaluated the efficacy of semaglutide once-weekly in treatment-seeking patients with alcohol use disorder and comorbid obesity. METHODS: In a 26-week, single-centre, randomised, double-blinded, placebo-controlled trial, treatment-seeking participants with moderate to severe alcohol use disorder and comorbid obesity were ass

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Negative / Null Result ReportOpen accessMedicine

Mitochondrial Health Through Nicotinamide Riboside and Berberine: Shared Pathways and Therapeutic Potential

F Visalli, Matteo Capobianco, F. Cappellani et al. · 2026 · International Journal of Molecular Sciences

Mitochondrial dysfunction represents a central hallmark of aging and a broad spectrum of chronic diseases, ranging from metabolic to neurodegenerative and ocular disorders. Nicotinamide riboside (NR), a vitamin B3 derivative and efficient precursor of NAD+ (nicotinamide adenine dinucleotide), and berberine (BBR), an isoquinoline alkaloid widely investigated in metabolic regulation, have independently emerged as promising mitochondrial modulators. NR enhances cellular NAD+ pools, thereby activating sirtuin-dependent pathways, stimulating PGC-1α–mediated mitochondrial biogenesis, and triggering

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Negative / Null Result ReportOpen accessMedicine

Performance and challenges of malaria rapid diagnostic tests in endemic regions of Africa

Fiyinfoluwa Demilade Ojeniyi, Adeola Oluwakemi Ayoola, Olajumoke Ibitoye et al. · 2025 · Scientific Reports

Rapid diagnostic tests (RDTs) have revolutionized malaria diagnosis, playing a crucial role in improving timely treatment and supporting surveillance efforts, especially in resource-limited settings. However, the performance of RDTs can…

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