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Failure-mode index

Search what already failed

A searchable index of real negative results, null findings, and replication failures from the published literature — so you can learn what didn't work before repeating it.

WASTE indexes published research — it does not host or republish full papers. Each entry is a metadata record (title, authors, DOI) compiled from open scholarly databases, with the abstract shown in full only where the paper is openly licensed (e.g. Creative Commons); otherwise a short excerpt is shown for reference under fair use. WASTE classifies each work by failure type; classifications are automated and approximate.

21252 results · page 150 of 709

Negative / Null Result ReportOpen accessNeuroscience

The myth of the Bayesian brain

Madhur Mangalam · 2025 · European Journal of Applied Physiology

The Bayesian brain hypothesis-the idea that neural systems implement or approximate Bayesian inference-has become a dominant framework in cognitive neuroscience over the past two decades. While mathematically elegant and conceptually unifying, this paper argues that the hypothesis occupies an ambiguous territory between useful metaphor and testable, biologically plausible mechanistic explanation. We critically examine the key claims of the Bayesian brain hypothesis, highlighting issues of unfalsifiability, biological implausibility, and inconsistent empirical support. The framework's remarkabl

View details →DOI: 10.1007/s00421-025-05855-6Cited by 10
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

View details →DOI: 10.1016/j.biopsych.2025.06.011Cited by 10
Negative / Null Result ReportOpen accessMedicine

PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2

Marwah Karim, Manjari Mishra, Chieh‐Wen Lo et al. · 2025 · Nature Communications

In search for broad-spectrum antivirals, we discover a small molecule inhibitor, RMC-113, that potently suppresses the replication of multiple RNA viruses including SARS-CoV-2 in human lung organoids. We demonstrate selective inhibition of…

View details →DOI: 10.1038/s41467-025-61759-1Cited by 10
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…

View details →DOI: 10.1007/s10620-025-09099-4Cited by 10
Negative / Null Result ReportOpen accessMedicine

Pulmonary Hypertension Associated with Interstitial Lung Disease (PH-ILD): Back to the Future

Giordano Fiorentù, Nicol Bernardinello, Giacomo Giulianelli et al. · 2025 · Advances in Therapy

Pulmonary hypertension (PH) is a progressive syndrome characterized by increased pulmonary artery pressure. PH often complicates chronic lung diseases, thus contributing to a substantial disease burden and poor prognosis. The WHO Group 3…

View details →DOI: 10.1007/s12325-025-03129-3Cited by 10
Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

The gut–brain connection: microbes’ influence on mental health and psychological disorders

Pegah Ataei, Hamidreza Kalantari, Tamara S. Bodnar et al. · 2026 · Frontiers in Microbiomes

The human gut microbiome has emerged as a pivotal modulator of brain function and mental health, acting through intricate bidirectional communication along the gut-brain axis. Mounting evidence suggests that microbial communities influence neurodevelopment, neurotransmission, and behavior via pathways involving the vagus nerve, immune signaling, and microbiota-derived metabolites such as short-chain fatty acids and neurotransmitter precursors. This review critically examines the mechanistic underpinnings of microbiota-brain communication and evaluates current findings linking dysbiosis to psyc

View details →DOI: 10.3389/frmbi.2025.1701608Cited by 10
Negative / Null Result ReportOpen accessMedicine

Meningioma: Novel Diagnostic and Therapeutic Approaches

Carlen Yuen, Michelle Zheng, Max Saint-Germain et al. · 2025 · Biomedicines

Background/Objectives: Meningiomas are the most common intracranial tumors. Surgery and radiation therapy are the cornerstones of treatment and no standard of care therapy exists for refractory meningiomas. This manuscript aims to provide a comprehensive review of novel diagnostic and therapeutic approaches against these tumors. Methods: A search for the existing literature on systemic therapies for meningiomas was performed on PubMed and a search for presently accruing clinical trials was performed on ClinicalTrials.gov. Results: Systemic treatments, including chemotherapy, somatostatin analo

View details →DOI: 10.3390/biomedicines13030659Cited by 10
Negative / Null Result ReportOpen accessEarth and Planetary Sciences

Confidence-guided cryo-EM map optimisation with LocScale-2.0

Alok Bharadwaj, R. de Bruin, Arjen J. Jakobi · 2026 · Nature Communications

Cryogenic sample electron microscopy (cryo-EM) maps often display uneven quality, with high-resolution features coexisting alongside weak or poorly ordered regions. Such variation complicates structural interpretation, especially for heterogeneous macromolecular assemblies. Here, we present LocScale-2.0, a context-aware map optimisation framework that operates without prior knowledge of molecular structure or composition. By leveraging general expectations of electron scattering by biological macromolecules, it enhances local detail and connectivity while preserving weak but biologically relev

View details →DOI: 10.1038/s41467-026-75327-8Cited by 10
Negative / Null Result ReportOpen accessHealth Professions

Enhancing Patient Education with AI: A Readability Analysis of AI-Generated Versus American Academy of Ophthalmology Online Patient Education Materials

Allison Kufta, Ali R. Djalilian · 2025 · Journal of Clinical Medicine

Background/Objectives: Patient education materials (PEMs) in ophthalmology often exceed recommended readability levels, limiting accessibility for many patients. While organizations like the AAO provide relatively easy-to-read resources, topics remain limited, and other associations’ PEMs are too complex. AI chatbots could help clinicians create more comprehensive, accessible PEMs to improve patient understanding. This study aims to compare the readability of patient education materials (PEMs) written by the American Academy of Ophthalmology (AAO) with those generated by large language models

View details →DOI: 10.3390/jcm14196968Cited by 10
Negative / Null Result ReportOpen accessNeuroscience

Memory out of context: Spacing effects and decontextualization in a computational model of the medial temporal lobe

James W. Antony · 2026

Abstract Some neural representations change across multiple timescales. Here we argue that modeling this “drift” could help explain the spacing effect (the long-term benefit of distributed learning), whereby differences between stored and current temporal context activity patterns produce greater error-driven learning. We trained a neurobiologically realistic model of the entorhinal cortex and hippocampus to learn paired associates alongside temporal context vectors that drifted between learning episodes and/or before final retention intervals. In line with spacing effects, greater drift led t

View details →DOI: 10.21428/8e6ba8ef.d9f5dd19Cited by 10
Negative / Null Result ReportOpen accessEarth and Planetary Sciences

Sweet and fatty symbionts: Photosynthetic productivity and carbon storage boosted in microalgae within a host

Andrea Catacora‐Grundy, Caroline Juery, Fabien Chevalier et al. · 2026 · Proceedings of the National Academy of Sciences

Abstract Symbiosis between a host and intracellular eukaryotic microalgae is a widespread life strategy in aquatic ecosystems. This partnership is considered to be mainly energized by the photosynthetically-derived carbon energy of…

View details →DOI: 10.1073/pnas.2513679123Cited by 10
Negative / Null Result ReportOpen accessArts and Humanities

Examining the impact of corporate social advocacy (CSA) issue ownership and message content on authenticity perceptions and behavioral intentions

Holly Overton, Michail Vafeiadis, Pratiti Diddi et al. · 2025 · Corporate Communications An International Journal

Purpose As companies continue to engage in CSA, they continue to struggle with determining what issues they should speak out about and how they can create compelling messages that inspire action. Guided by arguments from issue ownership theory, this study examines CSA message content effects related to two different social-political issues on advocacy behavioral intentions, megaphoning, brand preference and purchase intention. Specifically, the level of advocacy in a CSA message is examined, as well as the manner in which the message is written (narrative vs informational). Furthermore, this s

View details →DOI: 10.1108/ccij-05-2024-0080Cited by 10
Negative / Null Result ReportOpen accessEnergy

Astaxanthin from Haematococcus pluvialis and Chromochloris zofingiensis: Biosynthetic Pathways, Engineering Strategies, and Industrial Prospects

Shufang Yang, Xue Lu, Jia Wang et al. · 2025 · Marine Drugs

Astaxanthin, a high-value keto-carotenoid with potent antioxidant and health-promoting properties, has gained global attention as a sustainable nutraceutical and biotechnological product. The green microalgae Haematococcus pluvialis and Chromochloris zofingiensis represent two promising natural producers, yet they differ markedly in physiology, productivity, and industrial scalability. This review provides a focused comparative analysis of these two species, emphasizing their quantitative performance differences. H. pluvialis can accumulate astaxanthin up to ~3–5% of dry biomass but typically

View details →DOI: 10.3390/md23120485Cited by 10
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

View details →DOI: 10.3390/ph18101467Cited by 10
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

View details →DOI: 10.1038/s41413-025-00481-6Cited by 10
Negative / Null Result ReportOpen accessNeuroscience

Melatonin as a Guardian of Mitochondria: Mechanisms and Therapeutic Potential in Neurodegenerative Diseases

Yanyu Bao, Guoying Miao, Nannan He et al. · 2026 · Biology

Mitochondrial dysfunction is a key early pathological process in neurodegenerative diseases (NDs), leading to oxidative stress, impaired energy metabolism, and neuronal apoptosis prior to the onset of clinical symptoms. Although mitochondria represent important therapeutic targets, effective interventions targeting mitochondrial function remain limited. This review summarizes current evidence regarding the mechanisms by which melatonin protects mitochondria and evaluates its therapeutic relevance, with a primary focus on Alzheimer's disease, Parkinson's disease, and Huntington's disease-the ma

View details →DOI: 10.3390/biology15020189Cited by 10
Negative / Null Result ReportOpen accessPsychology

Does baseline severity interact with the effects of psychotherapy for depression? A meta-analytic review

Pim Cuijpers, Mathias Harrer, Clara Miguel et al. · 2026 · Journal of Affective Disorders

It is not yet clear whether baseline severity is associated with the effects of psychotherapies. We examined baseline severity at the study level in a large sample of randomized controlled trials comparing psychotherapies against a control condition for the treatment of depression. We used an existing large database of randomized trials comparing psychotherapies for depression with control groups ( www.metapsy.org ). We converted baseline severity scores across different depression measures into a common metric. We ran bivariable and multivariable meta-regression analyses to examine the associ

View details →DOI: 10.1016/j.jad.2025.121106Cited by 9
Negative / Null Result ReportOpen accessNursing

Exploring the use of FTIR Amide I band deconvolution to investigate protein secondary structure and texturisation during high moisture extrusion

Clara Barnés-Calle, P. Gou, E. Fulladosa et al. · 2026 · Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy

Fourier transform infrared spectroscopy (FTIR) combined with Amide I band deconvolution has been used to investigate protein structural changes occurring during high moisture extrusion processing (HMEP). However, it is a sensitive,…

View details →DOI: 10.1016/j.saa.2026.127509Cited by 9
Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Population Genetics and Trajectory Simulation Reveals the Invasion Process of the Fall Armyworm ( Spodoptera frugiperda ) in the Eastern Hemisphere

Pengfei Fu, Xijie Li, Zhongxiang Sun et al. · 2025 · Evolutionary Applications

As a migratory agricultural pest, the fall armyworm has been in the spotlight since it invaded Africa in 2016. Invasive populations have now colonized much of the Eastern Hemisphere, causing severe damage to a wide range of crops. However, there is still disagreement internationally on the origin and mode of invasion of fall armyworm populations, especially from the Americas to China. In this study, we provided an in-depth insight into the invasion of the fall armyworm in the Eastern hemisphere based on genome-wide data from 124 fall armyworm individuals collected from 14 sites across three co

View details →DOI: 10.1111/eva.70086Cited by 9
Negative / Null Result ReportOpen accessMedicine

Efeito de um novo produto fermentado de soja, enriquecido com isoflavonas e cálcio, sobre o tecido ósseo de ratas

Raquel Bedani, Elizeu Antônio Rossi, José Salvador Lepera et al. · 2026 · Archivos Latinoamericanos de Nutrición

The objective was to evaluate the effect of soy fermented product intake on the corporal weight and bone tissue of ovariectomized mature rats. This product was fermented with Enterococcus faecium and Lactobacillus jugurti and enriched with…

View details →DOI: 10.37527/2006.56.2.006Cited by 9
Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Human cancer genomes harbor the mutational signature of tobacco-specific nitrosamines NNN and NNK

Michael Korenjak, Nuri A. Temiz, Stéphane Keïta et al. · 2026 · Genome Medicine

BACKGROUND: Tobacco use is linked to multiple cancer types and a quarter of cancer deaths. Tobacco smoke contains numerous mutagenic chemicals such as polycyclic aromatic hydrocarbons (PAH), however, the mutagenicity of many chemicals in…

View details →DOI: 10.1186/s13073-026-01685-zCited by 9
Negative / Null Result ReportOpen accessPsychology

Virtual reality training to improve socio‐emotional functioning in adolescents with developmental language disorders: A multiple baseline effectiveness study

E. G. J. M. Arts, Bram Orobio de Castro, Ellen Luteijn et al. · 2024 · Social Development

Abstract This study investigated whether interactive virtual reality (VR) training of social and emotional abilities (InterAction) improves socio‐emotional functioning of youth with developmental language disorders (DLD). To this end we conducted a multiple baseline intervention study, comparing participants’ social abilities during a baseline phase with their changes in abilities during the intervention and posttest phase. The training group consisted of 29 adolescents ( 20 boys, 9 girls ) with DLD from the Netherlands. The training consisted of nine, weekly (45–50 min) individual sessions wi

View details →DOI: 10.1111/sode.12784Cited by 9
Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Altitude hypoxia and hypoxemia: pathogenesis and management

Chunmei Cai, Guohua Ni, Lei Chen et al. · 2026 · Signal Transduction and Targeted Therapy

At high altitudes, which typically exceed 2500 m, approximately 80 million people reside permanently, with over a million visitors annually. The primary effect of high altitude is hypobaric hypoxia, which leads to decreased oxygen availability and a cascade of physiological responses. However, inadequate or excessive responses can lead to malacclimatization, resulting in hypoxemia and various high-altitude illnesses, including acute mountain sickness (AMS), high-altitude cerebral edema (HACE), high-altitude pulmonary edema (HAPE), chronic mountain sickness (CMS), and high-altitude pulmonary hy

View details →DOI: 10.1038/s41392-025-02531-1Cited by 9
Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Gut‒heart axis: emerging therapies targeting trimethylamine N-oxide production

Efrain Ricardo Torres, Jennifer Wilcox, W. H. Wilson Tang · 2025 · Gut Microbes

Trimethylamine N-oxide (TMAO) has garnered considerable attention because of its role in the pathophysiology and pathogenesis of various disorders, particularly heart and kidney disease. Gut microbes produce trimethylamine (TMA) moieties from common dietary precursors, such as choline or carnitine, which are subsequently metabolized by the liver into TMAO. Circulating TMAO then exerts various effects, influencing dyslipidemia, metabolic syndrome, endothelial dysfunction, and inflammation, as well as other detrimental processes. Many existing medications have been shown to decrease TMAO levels

View details →DOI: 10.1080/19490976.2025.2604868Cited by 9
Negative / Null Result ReportOpen accessMedicine

Anti-inflammatory agents for the management of COPD - Quo Vadis?

Agamemnon Bakakos, Zoi Sotiropoulou, Nektarios Anagnostopoulos et al. · 2025 · Respiratory Medicine

Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality around the globe. Its main characteristics are persistent respiratory symptoms and progressive airflow limitation, both of which are driven by chronic inflammation. Despite the use of maximum bronchodilation and in selected patients inhaled corticosteroids (ICS), current therapies neither halt disease progression nor prevent exacerbations and loss of lung function. Recent research has focused on developing novel anti-inflammatory agents targeting specific pathways implicated in COPD pathogenesis, ai

View details →DOI: 10.1016/j.rmed.2025.108396Cited by 9
Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Gene therapy for Duchenne muscular dystrophy

Yuko Shimizu‐Motohashi · 2025 · Brain and Development

Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder caused by variants of the DMD that leads to progressive muscle degeneration. Recent advances in gene therapy have opened new therapeutic avenues, particularly through the use of adeno-associated virus (AAV)-mediated micro-dystrophin delivery. Delandistrogene moxeparvovec, the first FDA-approved gene therapy for DMD, has demonstrated transgene expression and potential functional improvement in early phase trials, although its long-term efficacy, durability, and safety remain unconfirmed. Immune-mediated toxicities including

View details →DOI: 10.1016/j.braindev.2025.104424Cited by 9
Negative / Null Result ReportOpen accessMedicine

SGLT-2 Inhibitors and GLP-1 Receptor Agonists as Combination Therapy in Type 2 Diabetes

Aris Liakos, Thomas Karagiannis, Ioannis Avgerinos et al. · 2026 · Current Diabetes Reports

PURPOSE OF REVIEW: The pharmacologic management of type 2 diabetes prioritises sodium-glucose cotransporter 2 (SGLT-2) inhibitors or glucagon-like peptide 1 (GLP-1) receptor agonists for their demonstrated cardiovascular benefits in individuals with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors, chronic kidney disease, and heart failure. However, while current guidelines recommend these drug classes alone, combination therapy is not explicitly advocated. Herein we summarise the rationale and available evidence in support for combination therapy. RECENT FINDINGS

View details →DOI: 10.1007/s11892-025-01616-zCited by 9
Negative / Null Result ReportOpen accessMedicine

Improving medication adherence in type 2 diabetes: strategies for better clinical and economic outcomes

Patrick Highton, Mark P. Funnell, Pankaj Gupta et al. · 2025 · Diabetologia

Abstract Medication adherence is critical for optimal glycaemic management and the prevention of complications in type 2 diabetes mellitus. Despite its importance, non-adherence remains a prevalent issue, with global estimates suggesting that approximately 38% of people with type 2 diabetes do not take their medications as prescribed, although estimates vary widely due to a range of patient-related, socioeconomic, condition-related (e.g. chronicity, severity of comorbidities) and healthcare system factors. This review synthesises the current evidence on the prevalence of non-adherence in type

View details →DOI: 10.1007/s00125-025-06617-xCited by 9
Negative / Null Result ReportOpen accessHealth Professions

Insights into Photo Degradation and Stabilization Strategies of Antibody–Drug Conjugates with Camptothecin Payloads

Shukun Luo, Joshua Bulos, Ricky Uroza et al. · 2025 · Pharmaceutics

Background: Photostability assessment is a critical component in the development of drug products, particularly for antibody–drug conjugates (ADCs) containing light-sensitive small molecules such as camptothecin (CPT) and its derivatives. ADCs conjugated with CPT derivative payloads often require extensive formulation and drug product development to ensure product stability due to their unique light-induced degradation pathways. In this study, we assessed the photostability of two ADC molecules with a CPT derivative payload (deruxtecan, DXd). Methods: Following light exposure, the stability of

View details →DOI: 10.3390/pharmaceutics17111397Cited by 9
Negative / Null Result ReportOpen accessEngineering

Review on Thermal Stimulation in Deep Geothermal Reservoirs: Thermo-Mechanical Mechanisms and Fracture Evolution

Kaituo Li, Lin Zhu, Fei Xiong et al. · 2026 · Processes

Enhanced geothermal systems (EGS) are a key technology for developing deep geothermal resources, yet they face significant challenges in constructing efficient thermal reservoirs within high-stress, high-strength, and low-permeability crystalline rock formations. Traditional hydraulic fracturing (HF) techniques encounter deep challenges in these environments, including excessively high fracturing pressures, limited fracture network patterns, and the risk of induced seismicity. This paper reviews the multi-scale thermal-mechanical mechanisms, fracture evolution patterns, and control strategies

View details →DOI: 10.3390/pr14081199Cited by 9