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Browse the failure-mode index

414 real negative results, null findings, and replication failures in Biochemistry, Genetics and Molecular Biology. 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.

Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Across-country genomic prediction of bull fertility in Jersey dairy cattle

Fernanda Marcondes de Rezende, M. Haile‐Mariam, J.E. Pryce et al. · 2020 · Journal of Dairy Science

The use of information across populations is an attractive approach to increase the accuracy of genomic predictions for numerically small breeds and traits that are time-consuming and difficult to measure, such as male fertility in cattle.…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Gut Microbiota-Derived Short-Chain Fatty Acids in Inflammatory Bowel Disease: Mechanistic Insights into Gut Inflammation, Barrier Function, and Therapeutic Potential

Roberta Ottria, Susan Mirmajidi, Pierangela Ciuffreda · 2026 · International Journal of Molecular Sciences

This review delves into the complex relationship between short-chain fatty acids (SCFAs) produced by the gut microbiota and inflammatory bowel disease (IBD). IBD, which includes Crohn's disease and ulcerative colitis, is a group of chronic gastrointestinal disorders with an increasing global incidence. Despite extensive research, the exact etiopathogenesis remains elusive, although a complex interplay involving genetic predisposition, environmental influences, and abnormal immune responses against commensal gut microbes is widely recognized. SCFAs, primarily acetate and butyrate, emerge as key

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

VEGF receptors mediate hypoxic remodeling of adult ovine carotid arteries

Olayemi O. Adeoye, Vincent Bouthors, Margaret C. Hubbell et al. · 2014 · Journal of Applied Physiology

Recent studies suggest that VEGF contributes to hypoxic remodeling of arterial smooth muscle, although hypoxia produces only transient increases in VEGF that return to normoxic levels despite sustained changes in arterial structure and…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Limited overlap between genetic effects on disease susceptibility and disease survival

Zhiyu Yang, Fanny‐Dhelia Pajuste, Kristina Zguro et al. · 2025 · Nature Genetics

Abstract Understanding disease progression is of high biological and clinical interest. Unlike disease susceptibility, whose genetic basis has been abundantly studied, less is known about the genetics of disease progression and its overlap with disease susceptibility. Considering nine common diseases ( n cases ranging from 11,980 to 124,682) across seven biobanks, we systematically compared genetic architectures of susceptibility and progression, defined as disease-specific mortality. We identified only one locus substantially associated with disease-specific mortality and showed that, at a si

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Androgen receptor‐positive, triple‐negative breast cancer

Ayca Gucalp, Tiffany A. Traina · 2017 · Cancer

Patients with triple-negative breast cancer (TNBC) generally are considered a single clinical subgroup, defined by the lack of receptor expression, and are uniformly treated with cytotoxic chemotherapy. However, the advent of molecular…

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Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology

Replication of plasmids derived from Shiga toxin-converting bacteriophages in starved Escherichia coli

Bożena Nejman-Faleńczyk, Beata Nadratowska-Wesołowska, Agnieszka Szalewska-Pałasz et al. · 2010 · Microbiology

The pathogenicity of Shiga toxin-producing Escherichia coli (STEC) depends on the expression of stx genes that are located on lambdoid prophages. Effective toxin production occurs only after prophage induction, and one may presume that…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Genome-wide association study of treatment-related toxicity two years following radiotherapy for breast cancer

Harkeran K. Jandu, Colin Veal, Laura Fachal et al. · 2023 · Radiotherapy and Oncology

Background and purpose Up to a quarter of breast cancer patients treated by surgery and radiotherapy experience clinically significant toxicity. If patients at high risk of adverse effects could be identified at diagnosis, their treatment could be tailored accordingly. This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity two years following whole breast radiotherapy. Materials and Methods A genome-wide association study (GWAS) was performed in 1,640 breast cancer patients with complete SNP, clinical, treatment and toxicity data, recruited a

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Phylogenetic Analysis of Murine Leukemia Virus Sequences from Longitudinally Sampled Chronic Fatigue Syndrome Patients Suggests PCR Contamination Rather than Viral Evolution

Aris Katzourakis, Stéphane Hué, Paul Kellam et al. · 2011 · Journal of Virology

Xenotropic murine leukemia virus (MLV)-related virus (XMRV) has been amplified from human prostate cancer and chronic fatigue syndrome (CFS) patient samples. Other studies failed to replicate these findings and suggested PCR contamination…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Pharmacoepigenetics of hypertension: genome-wide methylation analysis of responsiveness to four classes of antihypertensive drugs using a double-blind crossover study design

Marja-Liisa Nuotio, Heini Sánez Tähtisalo, Alexandra Lahtinen et al. · 2022 · Epigenetics

Essential hypertension remains the leading risk factor of global disease burden, but its treatment goals are often not met. We investigated whether DNA methylation is associated with antihypertensive responses to a diuretic, a beta-blocker, a calcium channel blocker or an angiotensin receptor antagonist. In addition, since we previously showed an SNP at the transcription start site (TSS) of the catecholamine biosynthesis-related ACY3 gene to associate with blood pressure (BP) response to beta-blockers, we specifically analysed the association of methylation sites close to the ACY3 TSS with BP

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Conceptual and methodological flaws undermine claims of a link between the gut microbiome and autism

Kevin J. Mitchell, Darren Dahly, Dorothy Bishop · 2025 · Neuron

The idea that the gut microbiome causally contributes to autism has gained currency in the scientific literature and popular press. Support for this hypothesis comes from three lines of evidence: human observational studies, preclinical experiments in mice, and human clinical trials. We critically assessed this literature and found that it is beset by conceptual and methodological flaws and limitations that undermine claims that the gut microbiome is causally involved in the etiology or pathophysiology of autism.

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Dual signaling pathways of TGF-β superfamily cytokines in hepatocytes: balancing liver homeostasis and disease progression

Roohi Chaudhary, Ralf Weiskirchen, Marcelo Ehrlich et al. · 2025 · Frontiers in Pharmacology

The transforming growth factor-β (TGF-β) superfamily (TGF-β-SF) comprises over 30 cytokines, including TGF-β, activins/inhibins, bone morphogenetic proteins (BMPs), and growth differentiation factors (GDFs). These cytokines play critical roles in liver function and disease progression. Here, we discuss Smad-dependent (canonical) and non-Smad pathways activated by these cytokines in a hepatocellular context. We highlight the connection between the deregulation of these pathways or the balance between them and key hepatocellular processes (e.g., proliferation, apoptosis, and epithelial-mesenchym

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

In vitro and in vivo activity of cefiderocol against Achromobacter spp. and Burkholderia cepacia complex, including carbapenem-non-susceptible isolates

Miki Takemura, Rio Nakamura, Merime Ota et al. · 2023 · Antimicrobial Agents and Chemotherapy

ABSTRACT Achromobacter spp. and Burkholderia cepacia complex (Bcc) are rare but diverse opportunistic pathogens associated with serious infections, which are often multidrug resistant. This study compared the in vitro antibacterial activity of the siderophore antibiotic cefiderocol against Achromobacter spp. and Bcc isolates with that of other approved antibacterial drugs, including ceftazidime-avibactam, ciprofloxacin, colistin, imipenem-relebactam, and meropenem-vaborbactam. Isolates were collected in the SIDERO multinational surveillance program. Among 334 Achromobacter spp. isolates [76.6%

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

A pharmacogenetic study of aldehyde oxidase I in patients treated with XK469

Jacqueline Ramı́rez, Tae Won Kim, Wanqing Liu et al. · 2013 · Pharmacogenetics and Genomics

XK469 (NSC 697887) is a selective topoisomerase II β inhibitor eliminated mainly by aldehyde oxidase I (AOX1). We performed a candidate gene study to investigate whether AOX1 genetic variation contributes to interindividual variability in…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Chronic intermittent hypoxia accelerates cardiac dysfunction and cardiac remodeling during cardiac pressure overload in mice and can be alleviated by PHD3 overexpression

Xuan Xu, Penghao Zhen, Fuchao Yu et al. · 2022 · Frontiers in Cardiovascular Medicine

Obstructive sleep apnea (OSA) accelerates the progression of chronic heart failure (CHF). OSA is characterized by chronic intermittent hypoxia (CIH), and CIH exposure accelerates cardiac systolic dysfunction and cardiac remodeling in a cardiac afterload stress mouse model. Mechanistic experiments showed that long-term CIH exposure activated hypoxia-inducible factor 1α (HIF-1α) expression in the mouse heart and upregulated miR-29c expression and that both HIF-1α and miR-29c simultaneously inhibited sarco-/endoplasmic reticulum calcium ATPase 2a (SERCA2a) expression in the mouse heart. Cardiac H

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Unraveling tumor specific neoantigen immunogenicity prediction: a comprehensive analysis

Guadalupe Nibeyro, Verónica M. Baronetto, Juan I. Folco et al. · 2023 · Frontiers in Immunology

Introduction: Identification of tumor specific neoantigen (TSN) immunogenicity is crucial to develop peptide/mRNA based anti-tumoral vaccines and/or adoptive T-cell immunotherapies; thus, accurate in-silico classification/prioritization proves critical for cost-effective clinical applications. Several methods were proposed as TSNs immunogenicity predictors; however, comprehensive performance comparison is still lacking due to the absence of well documented and adequate TSN databases. Methods: Here, by developing a new curated database having 199 TSNs with experimentally-validated MHC-I present

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Failed Experiment ReportOpen accessBiochemistry, Genetics and Molecular Biology

Genetic improvement of indigenous Greek sheep and goat breeds

Angeliki Argyriadou, Athanasios Ι. Gelasakis, Georgios Banos et al. · 2020 · Journal of the Hellenic Veterinary Medical Society

The objective of the study was twofold: (i) to review the genetics of production and resilience traits of indigenous Greek small ruminant breeds as well as the evolution of national breeding programs, and (ii) explore innovative and…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Cross-Ancestry DNA Methylation Marks of Insulin Resistance in Pregnancy: An Integrative Epigenome-Wide Association Study

Nicolás Fragoso-Bargas, Hannah R. Elliott, Sindre Lee-Ødegård et al. · 2022 · Diabetes

Although there are some epigenome-wide association studies (EWAS) of insulin resistance, for most of them authors did not replicate their findings, and most are focused on populations of European ancestry, limiting the generalizability. In…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Validation of Polygenic Risk Scores for Coronary Heart Disease in a Middle Eastern Cohort Using Whole Genome Sequencing

Mohamad Saad, Ayman El‐Menyar, Khalid Kunji et al. · 2022 · Circulation Genomic and Precision Medicine

Background: Enthusiasm for using polygenic risk scores (PRSs) in clinical practice is tempered by concerns about their portability to diverse ancestry groups, thus motivating genome-wide association studies in non-European ancestry…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

The gut-lung axis: effects and mechanisms of gut microbiota on pulmonary diseases

Jiayi Liu, Weichen Hong, Zhendong Sun et al. · 2026 · Frontiers in Immunology

The proposal of the gut-lung axis has profoundly reshaped our understanding of the mechanisms underlying respiratory diseases. As a crucial component of this axis, the gut microbiota plays a central role in pulmonary immune regulation through inter-organ communication mediated by metabolic products. However, a systematic integration of mechanisms explaining how gut microbes achieve precise cross-organ immune regulation remains elusive. Existing research predominantly focuses on descriptive observations, such as the association between early-life microbiota dysbiosis and an increased risk of as

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

A Deep Learning and Explainable AI-Based Approach for the Classification of Discomycetes Species

Aras Fahrettin Korkmaz, Fatih Ekinci, Şehmus Altaş et al. · 2025 · Biology

This study presents a novel approach for classifying Discomycetes species using deep learning and explainable artificial intelligence (XAI) techniques. The EfficientNet-B0 model achieved the highest performance, reaching 97% accuracy, a 97% F1-score, and a 99% AUC, making it the most effective model. MobileNetV3-L followed closely, with 96% accuracy, a 96% F1-score, and a 99% AUC, while ShuffleNet also showed strong results, reaching 95% accuracy and a 95% F1-score. In contrast, the EfficientNet-B4 model exhibited lower performance, achieving 89% accuracy, an 89% F1-score, and a 93% AUC. These

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Artificial Intelligence for Exosomal Biomarker Discovery for Cardiovascular Diseases: Multi-Omics Integration, Reproducibility, and Translational Prospects

Rasit Dinc, Nurittin Ardıç · 2026 · Cells

Exosomes and other extracellular vesicles (EVs) carry microRNAs, proteins, and lipids that reflect cardiovascular pathophysiology and can enable minimally invasive biomarker discovery. However, EV datasets are highly dimensional and heterogeneous, strongly influenced by pre-analytic variables and non-standardized isolation/characterization workflows, limiting reproducibility across studies. Artificial intelligence (AI), including machine learning (ML), deep learning (DL), and network-based approaches, can support EV biomarker development by integrating multi-omics profiles with clinical metada

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Directed Evolution Pipeline for the Improvement of Orthogonal Translation Machinery for Genetic Code Expansion at Sense Codons

Wil Biddle, David G. Schwark, Margaret A. Schmitt et al. · 2022 · Frontiers in Chemistry

The expansion of the genetic code beyond a single type of noncanonical amino acid (ncAA) is hindered by inefficient machinery for reassigning the meaning of sense codons. A major obstacle to using directed evolution to improve the efficiency of sense codon reassignment is that fractional sense codon reassignments lead to heterogeneous mixtures of full-length proteins with either a ncAA or a natural amino acid incorporated in response to the targeted codon. In stop codon suppression systems, missed incorporations lead to truncated proteins; improvements in activity may be inferred from increase

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Failed Experiment ReportOpen accessBiochemistry, Genetics and Molecular Biology

A Francisella tularensis Live Vaccine Strain That Improves Stimulation of Antigen-Presenting Cells Does Not Enhance Vaccine Efficacy

Deanna Schmitt, Dawn M. O’Dee, Joseph Horzempa et al. · 2012 · PLoS ONE

Vaccination is a proven strategy to mitigate morbidity and mortality of infectious diseases. The methodology of identifying and testing new vaccine candidates could be improved with rational design and in vitro testing prior to animal experimentation. The tularemia vaccine, Francisella tularensis live vaccine strain (LVS), does not elicit complete protection against lethal challenge with a virulent type A Francisella strain. One factor that may contribute to this poor performance is limited stimulation of antigen-presenting cells. In this study, we examined whether the interaction of genetical

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Comparing qPCR and DNA methylation-based measurements of telomere length in a high-risk pediatric cohort

Waylon J. Hastings, Laura Etzel, Christine M. Heim et al. · 2022 · Aging

Various approaches exist to assess population differences in biological aging. Telomere length (TL) is one such measure, and is associated with disease, disability and early mortality. Yet, issues surrounding precision and reproducibility are a concern for TL measurement. An alternative method to estimate TL using DNA methylation (DNAmTL) was recently developed. Although DNAmTL has been characterized in adult and elderly cohorts, its utility in pediatric populations remains unknown. We examined the comparability of leukocyte TL measurements generated using qPCR (absolute TL; aTL) to those esti

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Fusing metabolomics data sets with heterogeneous measurement errors

Sandra Waaijenborg, Oksana Korobko, Ko Willems van Dijk et al. · 2018 · PLoS ONE

Combining different metabolomics platforms can contribute significantly to the discovery of complementary processes expressed under different conditions. However, analysing the fused data might be hampered by the difference in their quality. In metabolomics data, one often observes that measurement errors increase with increasing measurement level and that different platforms have different measurement error variance. In this paper we compare three different approaches to correct for the measurement error heterogeneity, by transformation of the raw data, by weighted filtering before modelling

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Identifying statistically significant combinatorial markers for survival analysis

Raissa Relator, Aika Terada, Jun Sese · 2018 · BMC Medical Genomics

BACKGROUND: Survival analysis methods have been widely applied in different areas of health and medicine, spanning over varying events of interest and target diseases. They can be utilized to provide relationships between the survival time of individuals and factors of interest, rendering them useful in searching for biomarkers in diseases such as cancer. However, some disease progression can be very unpredictable because the conventional approaches have failed to consider multiple-marker interactions. An exponential increase in the number of candidate markers requires large correction factor

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Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology

Glycomacromolecules to Tailor Crowded and Heteromultivalent Glycocalyx Mimetics

Luca‐Cesare Blawitzki, Nina Bartels, Lorand Bonda et al. · 2024 · Biomacromolecules

The glycocalyx, a complex carbohydrate layer on cell surfaces, plays a crucial role in various biological processes. Understanding native glycocalyces' complexity is challenging due to their intricate and dynamic nature. Simplified mimics…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

CRISPR–Cas technologies in neurodegenerative disorders: mechanistic insights, therapeutic potential, and translational challenges

Raya Kh. Yashooa, Ari Q. Nabi, Shukur Wasman Smail et al. · 2026 · Frontiers in Neurology

CRISPR-Cas genome-editing technologies have emerged as powerful tools for precise DNA and RNA modulation, offering promising therapeutic strategies for neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). This review critically evaluates current CRISPR/Cas applications in neurodegeneration, with emphasis on mechanistic insights, therapeutic outcomes, and translational feasibility. Preclinical and early translational studies demonstrate that CRISPR-Cas platforms can correct pathogenic mutation

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Microbial diversification is maintained in an experimentally evolved synthetic community

Zahraa S. Al-tameemi, Alejandra Rodríguez‐Verdugo · 2024 · mSystems

ABSTRACT Microbial communities are incredibly diverse. Yet, the eco-evolutionary processes originating and maintaining this diversity remain understudied. Here, we investigate the patterns of diversification for Pseudomonas putida evolving in isolation and with Acinetobacter johnsonii leaking resources used by P. putida . We experimentally evolved four experimental replicates in monoculture and co-culture for 200 generations. We observed that P. putida diversified into two distinct morphotypes that differed from their ancestor by single-point mutations. One of the most prominent mutations hit

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