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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.

20211 results in Negative / Null Result Report · page 140 of 674

Negative / Null Result ReportOpen accessMedicine

Five‐Year Unified Risk Prediction Model for Gastric and Esophageal Cancer Based on Nationwide Health Check‐Up Data in Japan: J‐GESS Score

Kenta Watanabe, Sho Fukuda, Dai Kubota et al. · 2026 · Journal of Gastroenterology and Hepatology

BACKGROUND AND AIM: In Japan, gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC) account for nearly all fatal upper gastrointestinal malignancies. A unified model that simultaneously predicts the incidence of these two…

View details →DOI: 10.1111/jgh.70409Cited by 11
Negative / Null Result ReportOpen accessMathematics

The Evolution and Future Directions of PBPK Modeling in FDA Regulatory Review

Yong Li, Henry Sun, Zuoli Zhang · 2025 · Pharmaceutics

Background: Physiologically based pharmacokinetic (PBPK) modeling is a mathematical approach that integrates human physiological parameters with drug-specific characteristics (including both active pharmaceutical ingredients and excipients), and it has emerged as one of the core technologies for optimizing the efficiency and reliability of drug development. Methods: This study synthesizes applications of PBPK models in FDA-approved drugs (2020–2024), systematically analyzing model utilization frequency, indication distribution, application domains and choice of modeling platforms, to reveal th

View details →DOI: 10.3390/pharmaceutics17111413Cited by 11
Negative / Null Result ReportOpen accessMaterials Science

A 3D spheroid model for assessing nanocarrier-based drug delivery to solid tumors

Chitra Yadav, Alexander S. Evtushenko, Andrea Bistrović et al. · 2025 · npj Biomedical Innovations.

3D spheroid culture has emerged as a valuable tool for studying complex intratumoral processes and screening novel therapeutics in vitro. However, spheroids face reproducibility and data interpretation issues, which limit their utility. This work describes a simple and reproducible co-culture spheroid model compatible with high-throughput screening designed to study pancreatic ductal adenocarcinoma (PDAC), a highly therapy-resistant cancer. These spheroids, composed of both cancer and stromal cells, recapitulate key features of PDAC which are difficult to study in traditional 2D cell culture,

View details →DOI: 10.1038/s44385-025-00041-xCited by 11
Negative / Null Result ReportOpen accessAgricultural and Biological Sciences

Mechanism, Efficacy, and Safety of Natural Antibiotics

Andrei Teodor Matei, Anita Ioana Vișan · 2025 · Antibiotics

The growing ineffectiveness of common antibiotics against multidrug-resistant pathogens has made antimicrobial resistance (AMR) a serious global health concern. This review emphasizes that natural antibiotics from animals, bacteria, fungi, and plants are worthy alternatives for combating this crisis. Evolutionary pressure has shaped these molecules, leading to antibiotic-resistant bacteria that can withstand single-target synthetic drugs but are vulnerable to multiple attack pathways (e.g., cell wall disruption, protein synthesis inhibition, biofilm interference) from natural compounds. Natura

View details →DOI: 10.3390/antibiotics14100981Cited by 11
Negative / Null Result ReportOpen accessNeuroscience

Precision fMRI reveals that the language network exhibits adult-like left-hemispheric lateralization by 4 years of age

Ola Ozernov‐Palchik, Amanda O’Brien, Elizabeth Jiachen Lee et al. · 2026 · Nature Communications

In adults, left hemisphere (LH) damage often leads to aphasia, but many cases of early damage leave linguistic processing intact, with a functional language system developing in the right hemisphere. To explain this early apparent equipotentiality of the two hemispheres for language, some have proposed that the language system is more bilateral during early development and becomes increasingly left-lateralized with age. We examined language lateralization using fMRI in two large developmental cohorts (total n=273 children aged 4-16 years; n=107 adults). Strong, adult-like LH lateralization (in

View details →DOI: 10.1038/s41467-026-72916-5Cited by 11
Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Advances and Perspectives in Curcumin Regulation of Systemic Metabolism: A Focus on Multi-Organ Mechanisms

Dingya Sun, Jialu Wang, Xin Li et al. · 2026 · Antioxidants

Curcumin, a natural polyphenol derived from turmeric, functions as a potent exogenous antioxidant and exhibits a range of benefits in the prevention and management of metabolic diseases. Despite its extremely low systemic bioavailability, curcumin demonstrates significant bioactivity in vivo, a phenomenon likely attributable to its accumulation in the intestines and subsequent modulation of systemic oxidative stress and inflammation. This article systematically reviews the comprehensive regulatory effects of curcumin on systemic metabolic networks-including glucose metabolism, amino acid metab

View details →DOI: 10.3390/antiox15010109Cited by 11
Negative / Null Result ReportOpen accessMedicine

Conduction System vs Biventricular Pacing in Heart Failure

André Zimerman, Alexander Dal Forno, Luis E. Rohde et al. · 2026 · JAMA Cardiology

Importance: Conduction system pacing (CSP) is a promising and potentially cost-effective alternative to biventricular pacing (BiVP) in patients with heart failure with reduced ejection fraction (HFrEF) and left bundle-branch block (LBBB), but its impact on heart failure (HF) outcomes remains uncertain. Objective: To compare CSP vs BiVP on an HF-related outcome in patients with HFrEF and LBBB. Design, Setting, and Participants: PhysioSync-HF (Conduction System Pacing Versus Biventricular Resynchronization in Patients With Chronic Heart Failure) was an investigator-initiated, multicenter, noninf

View details →DOI: 10.1001/jamacardio.2026.0101Cited by 11
Negative / Null Result ReportOpen accessMedicine

Exercise blood pressure relative to fitness and cardiovascular outcomes: the EXERTION study

Martin G Schultz, Petr Otahal, Philip Roberts-Thomson et al. · 2025 · European Heart Journal

BACKGROUND AND AIMS: A hypertensive response to exercise is independently associated with cardiovascular disease (CVD), but clinical interpretation may be confounded by aerobic capacity (fitness). The aim of this study was to determine the relationship between exercise blood pressure (BP) relative to fitness and CVD events. METHODS: Clinical exercise test records were analysed from 12 743 people (aged 53 ± 13 years, 60% male) who completed a standard exercise stress test (Bruce treadmill protocol, stages 1-4) at six Australian hospitals. Records were linked to administrative datasets (hospital

View details →DOI: 10.1093/eurheartj/ehaf1082Cited by 11
Negative / Null Result ReportOpen accessAgricultural and Biological Sciences

Unravelling Changes in the Pinus radiata Root and Soil Microbiomes as a Function of Aridity

Sarah L. Addison, Zhenzhen Yan, Thomas F. Carlin et al. · 2025 · Global Change Biology

Increased aridity is emerging as a key impact of climate change in terrestrial ecosystems globally. Forest biomes are particularly vulnerable to the impacts of changing environmental conditions due to their long-lived and sessile nature.…

View details →DOI: 10.1111/gcb.70165Cited by 11
Negative / Null Result ReportOpen accessEnvironmental Science

Low molecular weight organic acids mobilize soil organic phosphorus for enzymatic hydrolysis in a temperate montane peatland

Yuchen Suo, Tong Li, Christian von Sperber et al. · 2025 · Biogeochemistry

Abstract The stability of carbon (C) stocks in peatlands is intricately linked to phosphorus (P) bioavailability. Given that organic P compounds (P o ) can make up to 89% of total soil P in these ecosystems, it is vital to understand their role in regulating plant productivity and organic matter decomposition. Despite this significance, the mechanisms controlling P bioavailability remain poorly understood. Plants and soil microorganisms primarily regulate the release of soil P via low-molecular-weight organic acids (LMWOAs) and modulate the hydrolysis of P o through phosphatase enzymes, partic

View details →DOI: 10.1007/s10533-025-01210-1Cited by 11
Negative / Null Result ReportOpen accessBusiness, Management and Accounting

The role of military directors in holding the CEO accountable for poor firm performance

Stevo Pavićević, Thomas Keil · 2024 · Strategic Management Journal

Abstract Research Summary Why do some boards of directors dismiss the CEO when a firm performs poorly, while others do not? We argue that military directors—outside directors with military backgrounds—on the board increase the likelihood…

View details →DOI: 10.1002/smj.3675Cited by 11
Negative / Null Result ReportOpen accessNeuroscience

TREM2 expression level is critical for microglial state, metabolic capacity and efficacy of TREM2 agonism

Astrid Feiten, Kilian Dahm, Kai Schlepckow et al. · 2026 · Nature Communications

Triggering receptor expressed on myeloid cells 2 (TREM2) is a central regulator of microglial activity and loss-of-function coding variants are major risk factors for late onset Alzheimer's disease (LOAD). To better understand the molecular and functional changes associated with TREM2 signalling in microglia, we generated a TREM2 reporter mouse. In APP transgenic animals, bulk RNA-sequencing of isolated microglia sorted based on reporter expression highlighted TREM2 level-related changes in major immunometabolic pathways, and enrichment of genes in oxidative phosphorylation and cholesterol met

View details →DOI: 10.1038/s41467-026-68706-8Cited by 11
Negative / Null Result ReportOpen accessMedicine

Leveraging radiotherapy to improve immunotherapy outcomes: rationale, progress and research priorities

Faith Hartley, Martin A. Ebert, Alistair Cook · 2025 · Clinical & Translational Immunology

The most successful immunotherapies for solid malignancies to date, immune checkpoint inhibitors, target the essential role of T cells in antitumor immunity. However, T-cell dysfunction presents a major hindrance to treatment efficacy, warranting research into combined treatment strategies for improving outcomes. The use of radiotherapy for this purpose has garnered much interest. Preclinical study has established that radiotherapy activates various immune mechanisms to improve T-cell activation, localisation and function within tumors, which improves response to immune checkpoint inhibitors.

View details →DOI: 10.1002/cti2.70030Cited by 11
Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Eco-evolutionary dynamics lead to functionally robust and redundant communities

Lorenzo Fant, Iuri Macocco, Jacopo Grilli · 2026 · PLoS Computational Biology

Microbial communities are taxonomically diverse and variable: species presence and abundances widely fluctuate over time, space, and even across biological replicates under controlled experimental conditions. However, environmental conditions exert strong selection on the traits of community members and their functions. Similar environmental conditions are expected to produce functionally similar communities. This environmental selection, combined with taxonomic variability, leads to the influential concept of functional redundancy - the idea that many species can perform the same function, al

View details →DOI: 10.1371/journal.pcbi.1014437Cited by 11
Negative / Null Result ReportOpen accessEngineering

Effect of TiO2 Content on the Arc-Erosion Resistance of Ag/SnO2 Electrical Contact Materials Prepared via Mechanical Alloying-Assisted Powder Metallurgy

Serkan Biyik, Murat Aydin · 2026 · Journal of Electronic Materials

Abstract In this study, the arc-erosion performances of AgSnO 2 -based electrical contact materials containing different amounts of titanium dioxide (TiO 2 ) were investigated using the mechanical alloying-assisted powder metallurgy method. For this purpose, composite powder synthesis was carried out through grinding experiments using a planetary ball mill, and the produced composite powders were subjected to molding and vacuum sintering processes. Subsequently, electrical wear tests were carried out under inductive loads to investigate the arc-erosion performance of composites. Scanning elect

View details →DOI: 10.1007/s11664-026-12701-8Cited by 11
Negative / Null Result ReportOpen accessEconomics, Econometrics and Finance

Green growth and sustainable energy transitions: evaluating the critical role of technology, resource efficiency, and innovation in Europe’s low-carbon future

Yangfan Lu, Sareer Ahmad, Shaista Noureen et al. · 2025 · Humanities and Social Sciences Communications

Renewable energy, technology, and innovation are central to sustainable development, but their effects vary by country because of institutional and economic differences. Previous studies often ignore these differences. By incorporating…

View details →DOI: 10.1057/s41599-025-05823-7Cited by 11
Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Origins of chromosome instability unveiled by coupled imaging and genomics

Marco Raffaele Cosenza, Alice Gaiatto, Büşra Erarslan Uysal et al. · 2025 · Nature

, the underlying processes and rates of spontaneous CA formation in human cells are underexplored. Here we introduce machine-learning-assisted genomics and imaging convergence (MAGIC)-an autonomously operated platform that integrates live-cell imaging of micronucleated cells, machine learning on-the-fly and single-cell genomics to systematically investigate CA formation. Applying MAGIC to near-diploid, non-transformed cell lines, we track de novo CAs over successive cell cycles, highlighting the common role of dicentric chromosomes as initiating events. We determine the baseline CA mutation ra

View details →DOI: 10.1038/s41586-025-09632-5Cited by 11
Negative / Null Result ReportOpen accessAgricultural and Biological Sciences

Branched-Chain Amino Acids in Parkinson’s Disease: Molecular Mechanisms and Therapeutic Potential

Hui-Yu Huang, Shu‐Ping Tsao, Tu‐Hsueh Yeh · 2025 · International Journal of Molecular Sciences

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra, resulting in motor symptoms such as bradykinesia, tremor, rigidity, and postural instability, as well as a wide variety of non-motor manifestations. Branched-chain amino acids (BCAAs)-leucine, isoleucine, and valine-are essential nutrients involved in neurotransmitter synthesis, energy metabolism, and cellular signaling. Emerging evidence suggests that BCAA metabolism is intricately linked to the pathophysiology of PD. Dysregulation of BCAA l

View details →DOI: 10.3390/ijms26146992Cited by 11
Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Host factors dictate gut microbiome alterations in chronic kidney disease more strongly than kidney function

Hubert Krukowski, Sophie Valkenburg, A. Vich Vila et al. · 2026 · Nature Microbiology

Despite recent progress, microbial associations reported in chronic kidney disease (CKD) remain inconsistent. Here we combined quantitative faecal metagenomics (n = 130) and cross-study biomarker comparisons (ntotal = 4,420) to study…

View details →DOI: 10.1038/s41564-026-02259-wCited by 11
Negative / Null Result ReportOpen accessEconomics, Econometrics and Finance

What Is the Cost of Privatization for Workers?

Martin Olsson, Joacim Tå̊g · 2025 · The Journal of Finance

ABSTRACT Privatization of state‐owned enterprises is on the agenda across the globe. Using Swedish data covering two decades, we show that productivity gains and headcount reductions are associated with economic costs for incumbent…

View details →DOI: 10.1111/jofi.13462Cited by 11
Negative / Null Result ReportOpen accessAgricultural and Biological Sciences

Exploring meat analogs: A review of alternative proteins with a focus on food safety and regulatory challenges

Tianyang Zhao, Noemí Echegaray, José M. Lorenzo et al. · 2025 · Food Control

Food safety and environmental concerns are global challenges that require innovative solutions, and alternative protein sources like insect proteins, plant-based meat analogs (PBMAs), and single-cell proteins represent promising pathways toward sustainable nutrition. These proteins are produced through different techniques including extrusion, fermentation, and cell cultivation, with emerging technologies like 3D printing and shear cell structuring enhancing their texture and nutritional quality. Beyond their technological advantages, these alternatives provide significant environmental benefi

View details →DOI: 10.1016/j.foodcont.2025.111777Cited by 11
Negative / Null Result ReportOpen accessMedicine

Association of the C-reactive protein–triglyceride–glucose index with metabolic dysfunction-associated steatotic liver disease and long-term all-cause and cardiovascular mortality: evidence from two nationwide prospective cohort studies

Xuefeng Jin, Zhaojie Su, Jian-Fa Zhong et al. · 2026 · Cardiovascular Diabetology

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to cardiometabolic disorders, and cardiovascular disease is the leading cause of death among affected individuals. Identifying simple biomarkers…

View details →DOI: 10.1186/s12933-026-03119-xCited by 11
Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Minimal residual disease in solid tumors: Clinical applications and future directions

Theresa Abdo, Ahmad Alhalabi, Sacha Yaghi et al. · 2026 · Cancer

Minimal residual disease (MRD) refers to the presence of residual cancer cells or tumor-derived fragments that persist after treatment and remain undetectable by conventional imaging or protein-based assays. Circulating tumor DNA (ctDNA)…

View details →DOI: 10.1002/cncr.70286Cited by 11
Negative / Null Result ReportOpen accessPhysics and Astronomy

Perihelion Asymmetry in the Water Production Rate of the Interstellar Object 3I/ATLAS

Hanjie Tan, Xiaoran Yan, Jian‐Yang Li · 2026 · The Astrophysical Journal Letters

Abstract 3I/ATLAS is an interstellar object whose activity provides critical insights into its composition and origin. However, due to its orbital geometry, the object is too close to the Sun near perihelion to be observed from the ground, and space-based measurements are therefore required. Here we characterize the water production rate of 3I/ATLAS using Solar and Heliospheric Observatory/SWAN Ly α observations from 2025 November to December (heliocentric distances 1.4–2.2 au) with 3D Monte Carlo modeling. We report a peak postperihelion water production rate of Q H 2 O ≈ 4 × 1 0 28 molecules

View details →DOI: 10.3847/2041-8213/ae3c97Cited by 11
Negative / Null Result ReportOpen accessPsychology

Think First, ChatGPT Later: Guiding Human–AI Collaboration for Learning Gains in Independent Human Creativity

Sarah Shi Hui Wong, Sophia Xuefei Qiu · 2026 · Educational Psychology Review

Abstract Generative artificial intelligence (AI) tools such as ChatGPT can boost creative performance, but do these boosts translate into learning gains? This study examined whether the benefits of ChatGPT for creativity persist even when its assistance is removed, and how people can effectively use ChatGPT to enhance their learning and independent creativity. University students ( N = 196) solved a creative product improvement task either independently (human-only group) or using ChatGPT freely (general-AI group) or using ChatGPT in a guided way (regulated-AI group). Specifically, the regulat

View details →DOI: 10.1007/s10648-026-10118-7Cited by 11
Negative / Null Result ReportOpen accessPhysics and Astronomy

Quasi-periodic pulsations in solar and stellar flares

Chloe E. Pugh · 2026 · Kyoto University Research Information Repository (Kyoto University)

Quasi-periodic pulsations (QPPs) are a phenomenon commonly observed in solar flares, and are also occasionally observed in stellar flares. They are time variations in the intensity of the flare emission that repeat with approximately…

View details →DOI: 10.82444/warw.33766342Cited by 11
Negative / Null Result ReportOpen accessNeuroscience

Sexual dimorphism in the complete Drosophila male central nervous system connectome

Stuart Berg, Isabella R. Beckett, Marta Costa et al. · 2026 · Cell

Sex differences in behavior exist across all animals, typically under strong genetic regulation. In Drosophila, fruitless/doublesex transcription factors identify dimorphic neurons, but their organization into functional circuits remains unclear. We present the connectome of the entire Drosophila male central nervous system. This contains 166,700 neurons spanning the brain and nerve cord, fully proofread and annotated, including fruitless/doublesex expression and 11,710 neuron types. We provide the first comprehensive comparison between male and female brain connectomes to synaptic resolution,

View details →DOI: 10.1016/j.cell.2026.08.015Cited by 11
Negative / Null Result ReportMedicine

Different organ-specific response to nivolumab to determine the survival outcome of patients with advanced hepatocellular carcinoma (aHCC).

Han Sang Kim, Jung Yong Hong, Jaekyung Cheon et al. · 2020 · Journal of Clinical Oncology

4584 Background: Previously, two phase III clinical trials of immune checkpoint inhibitors (ICI) failed to meet their primary endpoints, leading to doubts regarding the clinical activity of ICI monotherapy in patients with aHCC. Here, we…

View details →DOI: 10.1200/jco.2020.38.15_suppl.4584Cited by 11
Negative / Null Result ReportOpen accessEnvironmental Science

Association Between Living Environmental Factors and Stroke in Middle‐Aged and Older Chinese Adults: A Nationwide Prospective Cohort Study

Xinyue Huang, Bowen Yang, Nating Liu et al. · 2026 · Journal of the American Heart Association

BACKGROUND: The synergistic effects of multiple environmental factors on stroke remain unknown. The aim of this study was to explore the relationship between multiple living environment factors and stroke in middle-aged and older Chinese…

View details →DOI: 10.1161/jaha.125.043867Cited 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