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Browse the failure-mode index

473 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

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

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Accurate prediction of quantitative traits with failed SNP calls in canola and maize

Sven E. Weber, Harmeet Singh Chawla, Lennard Ehrig et al. · 2023 · Frontiers in Plant Science

In modern plant breeding, genomic selection is becoming the gold standard to select superior genotypes in large breeding populations that are only partially phenotyped. Many breeding programs commonly rely on single-nucleotide polymorphism (SNP) markers to capture genome-wide data for selection candidates. For this purpose, SNP arrays with moderate to high marker density represent a robust and cost-effective tool to generate reproducible, easy-to-handle, high-throughput genotype data from large-scale breeding populations. However, SNP arrays are prone to technical errors that lead to failed al

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Ten-year update of HOBOE phase III trial comparing triptorelin plus either tamoxifen or letrozole or zoledronic acid + letrozole in premenopausal hormone receptor-positive early breast cancer patients

Adriano Gravina, P. Gargiulo, Michelino De Laurentiis et al. · 2025 · ESMO Open

BACKGROUND: The Hormonal Bone Effects (HOBOE) study tested whether adjuvant triptorelin plus either letrozole (L) or zoledronic acid (Z) plus L (ZL) was more effective than tamoxifen (T) in premenopausal patients with hormone…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

The TEX44-CPT1B axis regulates mitochondrial sheath assembly and fatty acid oxidation in sperm

Erlei Zhi, Haowei Bai, Chuan Ren et al. · 2025 · Nature Communications

Mitochondrial fatty acid β-oxidation (FAO) is essential for energy production and cellular homeostasis, yet its role in sperm function has remained unclear. Through whole-exome sequencing (WES) of 800 patients with asthenozoospermia, we…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Associations of common variants in TAAR5, OR6C70, and GBA with hyposmia in Han Chinese individuals with Parkinson’s disease

Yi-Lun Ge, Pu-Zhi Wang, Jia-Hui Yan et al. · 2022 · Advanced Neurology

Hyposmia is one of the cardinal symptoms of Parkinson’s disease (PD), with a considerably high prevalence rate in PD individuals. However, some individuals still retain normal olfactory function. Recent studies have shown that genetic factors may play a role in such a phenomenon. This study aimed to explore the potential genetic factors underlying the variation of olfactory function among PD individuals. Two hundred and three Han Chinese individuals with PD were recruited into this study. All the individuals underwent detailed clinical assessment conducted by experienced neurologists

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Enhanced efficacy with azacytidine and oncolytic BHV-1 in a tolerized cotton rat model of breast adenocarcinoma

Breanne Cuddington, Meghan L. Verschoor, Ali A. Ashkar et al. · 2015 · Molecular Therapy — Oncolytics

Oncolytic viruses selectively replicate in cancer cells by exploiting biochemical differences between normal and tumor cells. Treatment with epigenetic modifiers such as 5-Azacytidine, a DNA methyltransferase inhibitor, increases the…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Targeted Hyaluronan Degradation Enhanced Tumor Growth Inhibition in Gastrointestinal Cancer Models

Fulai Zhou, Guangmao Mu, Honglei Bi et al. · 2025 · Cancers

Background. The dense hyaluronan (HA)-rich stroma in solid tumors can prevent effective tumor growth inhibition by hindering drug delivery and immune cell infiltration. However, the degradation of HA alone by systemic delivery of hyaluronidase has not shown significant improvement of tumor growth inhibition. Objectives/Methods. In this study, we targeted hyaluronan degradation by using antibody–enzyme (AbEn) molecules by fusing antibodies to a recombinant human hyaluronidase (HYAL). Results. The AbEn molecules were stable, retained both antigen-binding and enzymatic activities, and demonstrate

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Microbiota-Gut-Kidney Axis and Targeted Therapeutic Strategies in Kidney Diseases

Zhenghao Sun, Qian Gong, Zi-lai Wang et al. · 2026 · International Journal of Biological Sciences

The gut microbiota, as a source of profound genetic and metabolic capacity, affects every aspect of human biology including health, development and aging, as well as disease. Studies have demonstrated the crosstalk between the gut…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Nrf2-Activating Natural Compounds in Neurodegenerative Diseases: Targeting Oxidative Stress and Protein Aggregation

Lucia Chico, Erika Schirinzi, Linda Balestrini et al. · 2026 · International Journal of Molecular Sciences

Neurodegenerative diseases (NDs) are among the leading causes of disability and mortality worldwide and are characterized by multifactorial pathogenesis involving interconnected mechanisms, such as oxidative stress, protein misfolding and aggregation, neuroinflammation, and mitochondrial dysfunction. Dysregulation of transcription factors, governing cellular defense responses, particularly nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of antioxidant and proteostatic pathways, plays a critical role in neurodegenerative processes. Currently, available pharmacological treatm

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Distinct microbial mediators link diet to inflammation in Crohn’s disease and ulcerative colitis

L E Mayorga, Arnau Noguera Segura, Laura Campderros et al. · 2026 · Gut

BACKGROUND: Inflammatory bowel disease (IBD) arises from complex interactions among diet, host and gut microbiome. Although diet influences intestinal inflammation, the microbial and metabolic pathways involved, and their differences…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

In-depth comparison of commercial Trichoderma-based products: integrative approaches to quantitative analysis, taxonomy and efficacy

Tomasz Kulik, Paulina Staniszewska, Patryk Wiśniewski et al. · 2025 · Frontiers in Microbiology

Products derived from Trichoderma fungi, primarily marketed as biofungicides and biofertilizers, are widely utilized to promote sustainable and regenerative farming practices. In this study, we characterized Trichoderma -based products currently available in both international and local (the Polish) markets. We estimated the number of viable cells in these products, which is a key factor boosting their efficacy. We found substantial differences in the number of colony-forming units (CFUs) among various products, with all products exhibiting fewer CFUs than claimed. The degree of this inconsist

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Five‐Year Outcomes and Disease Trajectories in Moderate‐to‐Severe Ulcerative Colitis: A Korean Multicenter Inception Cohort

Byong Duk Ye, Hyo Jong Kim, Dongil Park et al. · 2026 · Journal of Gastroenterology and Hepatology

BACKGROUND AND AIM: The incidence of ulcerative colitis (UC) has been increasing in Asia. Comprehensive data on the long-term course of moderate-to-severe UC remain scarce. This study investigated the clinical outcomes and factors…

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Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology

Purinergic Signaling Regulates the Transforming Growth Factor-β3-Induced Chondrogenic Response of Mesenchymal Stem Cells to Hydrostatic Pressure

Andrew J. Steward, Daniel J. Kelly, Diane R. Wagner · 2016 · Tissue Engineering Part A

Although hydrostatic pressure (HP) is known to regulate chondrogenic differentiation of mesenchymal stromal/stem cells (MSCs), improved insight into the mechanotransduction of HP may form the basis for novel tissue engineering strategies.…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Transcriptome Profiling in Rat Inbred Strains and Experimental Cross Reveals Discrepant Genetic Architecture of Genome-Wide Gene Expression

Pamela J. Kaisaki, Georg Otto, Karène Argoud et al. · 2016 · G3 Genes Genomes Genetics

Abstract To test the impact of genetic heterogeneity on cis- and trans-mediated mechanisms of gene expression regulation, we profiled the transcriptome of adipose tissue in 20 inbred congenic strains derived from diabetic Goto–Kakizaki (GK) rats and Brown–Norway (BN) controls, which contain well-defined blocks (1–183 Mb) of genetic polymorphisms, and in 123 genetically heterogeneous rats of an (GK × BN)F2 offspring. Within each congenic we identified 73–1351 differentially expressed genes (DEGs), only 7.7% of which mapped within the congenic blocks, and which may be regulated in cis. The remai

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

A comparison of computational methods for expression forecasting

Eric Kernfeld, Yunxiao Yang, Joshua S. Weinstock et al. · 2025 · Genome biology

Diverse machine learning methods promise to forecast gene expression changes in response to novel genetic perturbations. However, these methods' accuracy is not well characterized. We created a benchmarking platform that combines a panel…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Highly ordered clustering of TNFα and BAFF ligand-receptor-intracellular adaptor complexes on a lipid membrane

Chan Seok Lim, Jisun Lee, Jisun Lee et al. · 2025 · Nature Communications

SUMMARY We report the cryo-EM structures of clusters of TNF receptor family proteins, TNFR1 and BAFFR. The receptor-ligand complexes were anchored to a flat lipid layer to mimic the membrane-bound state. We observed that the TNFα-TNFR1…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Oncolytic Viruses in Cancer Immunotherapy: From Molecular Engineering to Clinical Translation

Mohammad Fayyad‐Kazan, Sarah Ayad Al-Tameemi, Allal Ouhtit · 2026 · Cells

Cancer immunotherapy has transformed modern oncology, yet durable responses remain limited for many patients due to immune exclusion, adaptive resistance, and tumor heterogeneity. Oncolytic viruses (OVs) have emerged as a novel class of immunotherapeutics that unify direct tumor cytolysis with stimulation of antitumor immunity. By inducing immunogenic cell death (ICD) and releasing tumor-associated antigens (TAAs), OVs remodel the tumor microenvironment (TME) into an inflamed and immune-permissive niche capable of enabling systemic immune activation. Rapid advances in viral engineering have st

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Gut microbiome features associated with Bifidobacterium colonization predict personalized probiotic persistence patterns

Sourav Goswami, Alisha Ansari, Chetan Saraf et al. · 2026 · Nature Communications

Bifidobacteria are key health-associated members of the human gut microbiome and are widely used as probiotics, but their colonization success varies substantially between individuals, partly due to baseline microbiome composition. We…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Hypoxic microenvironment in cancer: role in metabolic reprogramming

Niti Sureka, Rashi Maheshwari, Amit H Agravat et al. · 2026 · Frontiers in Oncology

Hypoxia, a defining hallmark of solid tumors, arises from structurally and functionally abnormal vasculature, rapid cellular proliferation, and impaired perfusion, resulting in chronic and cycling oxygen deprivation within the tumor massThe hypoxic tumor microenvironment orchestrates extensive molecular reprogramming primarily through stabilization and activation of hypoxia-inducible factors (HIF-1α and HIF-2α), which regulate broad transcriptional networks governing metabolism, angiogenesis, stemness, invasion, and immune modulation. Under low oxygen tension, tumor cells shift toward aerobic

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

HDAC inhibitors as anticancer drugs: chemical diversity, clinical trials, challenges and perspectives

A. AbdAllah · 2026 · RSC Advances

In an attempt to collect clinical data about HDAC inhibitors as very significant anticancer drugs we aimed to compare data and reveal the impact of the structural features, concluding the points of interest that are likely to help further development of better cancer therapy. We presented results of different clinical phases of HDAC inhibitors classified as hydroxamic acid derivatives, cyclic peptides, benzamides, and short chain aliphatic acids in a coherent and cohesive manner. It was found that HDAC inhibitors are preferentially combined with other antitumor drugs, mainly anti PD-1 and doxo

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Metabolic modeling reveals determinants of prebiotic and probiotic treatment efficacy across multiple human intervention trials

Nick Quinn-Bohmann, Alex V. Carr, Sean M. Gibbons · 2026 · PLoS Biology

Prebiotic, probiotic, and combined (synbiotic) interventions often show variable outcomes across individuals, driven by complex interactions between introduced biotics, the endogenous microbiota, and the host diet. Predicting individual-specific success or failure of probiotic and prebiotic therapies remains a major challenge. Here, we leverage microbial community-scale metabolic models (MCMMs) to predict probiotic engraftment and microbiota-mediated short-chain fatty acid (SCFA) production in response to probiotic and prebiotic interventions. Using data from two human clinical trial cohorts,

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Mutational scanning reveals oncogenic CTNNB1 mutations have diverse effects on signaling

Anagha Krishna, Alison Meynert, Karamjit Singh Dolt et al. · 2026 · Nature Genetics

CTNNB1, the gene encoding β-catenin, is a frequent target for oncogenic mutations activating the canonical Wnt signaling pathway, typically through missense mutations within a degron hotspot motif in exon 3. Here, we combine saturation genome editing with a fluorescent reporter assay to quantify signaling phenotypes for all 342 possible missense mutations in the mutation hotspot. Our data define the genetic requirements for β-catenin degron function, refine the consensus motif for substrate recognition by β-TRCP and reveal diverse levels of signal activation among known driver mutations. Tumor

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

New medications development for smoking cessation

Dana Lengel, Paul J. Kenny · 2023 · Addiction Neuroscience

Diseases associated with nicotine dependence in the form of habitual tobacco use are a major cause of premature death in the United States. The majority of tobacco smokers will relapse within the first month of attempted abstinence.…

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