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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

Genome-wide association study identifies common variants associated with breast cancer in South African Black women

M Hayat, Wenlong Carl Chen, Chantal Babb de Villiers et al. · 2025 · Nature Communications

Abstract Genome-wide association studies (GWAS) have characterized the contribution of common variants to breast cancer (BC) risk in populations of European ancestry, however GWAS have not been reported in resident African populations. This GWAS included 2485 resident African BC cases and 1101 population matched controls. Two risk loci were identified, located between UNC13C and RAB27A on chromosome 15 (rs7181788, p = 1.01 × 10 −08 ) and in USP22 on chromosome 17 (rs899342, p = 4.62 × 10 −08 ). Several genome-wide significant signals were also detected in hormone receptor subtype analysis. The

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

The HDAC inhibitor romidepsin renders liver cancer vulnerable to RTK targeting and immunologically active

Celia Sequera, Margherita Grattarola, Floriane Cannet et al. · 2025 · Nature Communications

Histone deacetylases (HDACs) are epigenetic regulators frequently altered in cancer. Here we report that overexpression of HDAC1/2 occurs in Hepatocellular Carcinoma (HCC) patients, correlating with poor prognosis. We show that romidepsin,…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Population Levels Assessment of the Distribution of Disease-Associated Variants With Emphasis on Armenians – A Machine Learning Approach

Maria Nikogհosyan, Siras Hakobyan, Anahit Hovhannisyan et al. · 2019 · Frontiers in Genetics

Background: During last decades a number of genome-wide association studies (GWAS) has identified numerous single nucleotide polymorphisms (SNPs) associated with different complex diseases. However, associations reported in one population are often conflicting and did not replicate when studied in other populations. One of the reasons could be that most of GWAS employ case-control design in one or a limited number of populations, but little attention was paid to global distribution of disease associated alleles across different populations. Moreover, the majority of GWAS have been performed on

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

PRKCZmethylation is associated with sunlight exposure in a North American but not a Mediterranean population

Stella Aslibekyan, Hassan S. Dashti, Toshiko Tanaka et al. · 2014 · Chronobiology International

Sunlight exposure has been shown to alter DNA methylation patterns across several human cell-types, including T-lymphocytes. Since epigenetic changes establish gene expression profiles, changes in DNA methylation induced by sunlight…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Diagnosis value of targeted and metagenomic sequencing in respiratory tract infection

Yukun Kuang, Weiping Tan, Chaohui Hu et al. · 2024 · Frontiers in Cellular and Infection Microbiology

Background: Targeted next-generation sequencing (tNGS) has become a trending tool in the field of infection diagnosis, but concerns are also raising about its performance compared with metagenomic next-generation sequencing (mNGS). This study aims to explore the clinical feasibility of a tNGS panel for respiratory tract infection diagnosis and compare it with mNGS in the same cohort of inpatients. Methods: 180 bronchoalveolar lavage fluid samples were collected and sent to two centers for mNGS and tNGS blinded tests, respectively. The concordance between pathogen reports of both methods and th

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Adjuvant chemotherapy could not bring survival benefit to HR-positive, HER2-negative, pT1b-c/N0–1/M0 invasive lobular carcinoma of the breast: a propensity score matching study based on SEER database

Guangfu Hu, Guangxia Hu, Chengjiao Zhang et al. · 2020 · BMC Cancer

BACKGROUND: The benefit of adjuvant chemotherapy in invasive lobular carcinoma (ILC) is still unclear. The objective of the current study was to elucidate the effectiveness of adjuvant chemotherapy in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1b-c/N0-1/M0 ILC. METHODS: Based on Surveillance, Epidemiology, and End-Results (SEER) database, we identified original 12,334 HR-positive, HER2-negative, pT1b-c/N0-1/M0 ILC patients, who were then divided into adjuvant chemotherapy group and control group. End-points were overall survival (OS) and breast

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Impact of transfer learning methods and dataset characteristics on generalization in birdsong classification

Burooj Ghani, Vincent J. Kalkman, Bob Planqué et al. · 2025 · Scientific Reports

Animal sounds can be recognised automatically by machine learning, and this has an important role to play in biodiversity monitoring. Yet despite increasingly impressive capabilities, bioacoustic species classifiers still exhibit imbalanced performance across species and habitats, especially in complex soundscapes. In this study, we explore the effectiveness of transfer learning in large-scale bird sound classification across various conditions, including single- and multi-label scenarios, and across different model architectures such as CNNs and Transformers. Our experiments demonstrate that

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Mutualism breakdown underpins evolutionary rescue in an obligate cross-feeding bacterial consortium

Ignacio J. Melero‐Jiménez, Yael Sorokin, Ami Merlin et al. · 2025 · Nature Communications

Populations facing lethal environmental change can escape extinction through rapid genetic adaptation, a process known as evolutionary rescue. Despite extensive study, evolutionary rescue is largely unexplored in mutualistic communities, where it is likely constrained by the less adaptable partner. Here, we explored empirically the likelihood, population dynamics, and genetic mechanisms underpinning evolutionary rescue in an obligate mutualism involving cross-feeding of amino acids between auxotrophic Escherichia coli strains. We found that over 80% of populations overcame a severe decline whe

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

The Road to Remyelination in Multiple Sclerosis: Breakthroughs, Challenges, and Considerations for Future Trial Design

Leah Zuroff, Vista Farkhondeh, Riley Bove et al. · 2025 · Drugs

Despite major advances in multiple sclerosis (MS) treatment, disability accumulation independent of relapse activity remains a significant challenge. Chronic demyelination is a key driver of neurodegeneration and disease progression,…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

New cycle, same old mistakes? Overlapping vs. discrete generations in long-term recurrent selection

Marlee R. Labroo, Jessica Rutkoski · 2022 · BMC Genomics

BACKGROUND: Recurrent selection is a foundational breeding method for quantitative trait improvement. It typically features rapid breeding cycles that can lead to high rates of genetic gain. Usually, generations are discrete in recurrent selection, which means that breeding candidates are evaluated and considered for selection for only one cycle. Alternately, generations can overlap, with breeding candidates considered for selection as parents for multiple cycles. With recurrent genomic selection but not phenotypic selection, candidates can be re-evaluated by using genomic estimated breeding v

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Factors correlating with significant differences between X-ray structures of myoglobin

Alexander A. Rashin, Marcin J. Domagalski, Michael T. Zimmermann et al. · 2014 · Acta Crystallographica Section D Biological Crystallography

Validation of general ideas about the origins of conformational differences in proteins is critical in order to arrive at meaningful functional insights. Here, principal component analysis (PCA) and distance difference matrices are used to…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Complex trait methylation scores in the prediction of major depressive disorder

Miruna C. Barbu, Carmen Amador, Alex S. F. Kwong et al. · 2022 · EBioMedicine

BACKGROUND: DNA methylation (DNAm) is associated with time-varying environmental factors that contribute to major depressive disorder (MDD) risk. We sought to test whether DNAm signatures of lifestyle and biochemical factors were associated with MDD to reveal dynamic biomarkers of MDD risk that may be amenable to lifestyle interventions. METHODS: , N=565), using CpG sites reported in previous well-powered methylome-wide association studies. We also compared their predictive accuracy for MDD to a MDD MS in an independent GS sub-sample (N=4,432). FINDINGS: =-0.069-0.083) remained significantly a

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

De novo and inherited dominant variants in U4 and U6 snRNA genes cause retinitis pigmentosa

Mathieu Quinodoz, Kim Rodenburg, Zuzana Cvačková et al. · 2026 · Nature Genetics

Small nuclear RNAs (snRNAs) combine with specific proteins to generate small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. U4 snRNA forms a duplex with U6 and, together with U5, contributes to the tri-snRNP…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Disruption of adenylyl cyclase type V does not rescue the phenotype of cardiac-specific overexpression of Gαqprotein-induced cardiomyopathy

Valeriy Timofeyev, C. A. Porter, Dipika Tuteja et al. · 2010 · American Journal of Physiology-Heart and Circulatory Physiology

Adenylyl cyclase (AC) is the principal effector molecule in the β-adrenergic receptor pathway. AC(V) and AC(VI) are the two predominant isoforms in mammalian cardiac myocytes. The disparate roles among AC isoforms in cardiac hypertrophy…

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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

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Research advances in the study of traditional Chinese medicine formula granules on signaling pathway-mediated disease mechanisms

Zhuoxu Gu, Zhonghao Wang, Xianquan Zhang et al. · 2025 · Frontiers in Pharmacology

As a modern dosage form of traditional Chinese medicine, Traditional Chinese Medicine Formula Granules (TCMFG) maximally retains active metabolites through standardized production processes, including dynamic countercurrent extraction and low-temperature concentration. This serves as a critical material basis for elucidating its multi-target regulatory mechanisms. Recent studies have highlighted the significant potential of TCMFG in treating complex diseases, such as inflammation, tumors, metabolic disorders, fibrosis, and orthopedic conditions like osteoarthritis and osteoporosis, by modulati

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Breaking the outer membrane barrier: structure, targets, and antimicrobial strategies for Gram-negative bacteria

Fanzhuo Xu, Yu Xie, Weiwei Yu et al. · 2026 · Frontiers in Microbiology

Multidrug resistance in Gram-negative bacteria has become a significant global public health challenge, threatening human health and clinical treatment outcomes. The unique outer membrane structure of these pathogens greatly limits antibiotic penetration, serving as the core mechanism of resistance. This paper systematically analyses antimicrobial strategies targeting the outer membrane of Gram-negative bacteria, mainly including: (1) directly disrupting the outer membrane structure and enhancing drug permeability; (2) inhibiting the biosynthesis or transport pathways of key outer membrane com

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Topological requirements of the mitochondrial heavy-strand promoters

Ornella Zollo, Neal Sondheimer · 2017 · Transcription

In vitro studies of mitochondrial transcription often use linear templates that fail to replicate key features of transcription on a circular genome. We developed a plasmid-based system for the analysis of heavy-strand promoters that…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Tetanus in the Elderly: The Management of Intensive Care and Prolonged Hospitalization

Hiroki Isono, Taiju Miyagami, Kohta Katayama et al. · 2016 · Internal Medicine

Tetanus is a potentially fatal infection. Approximately 100 cases are reported in Japan each year; however, little is known about its clinical course and outcomes in the current era of treatment. We herein report three cases of tetanus in…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Ex vivo infection model for Francisella using human lung tissue

Kristin Köppen, Diana Fatykhova, Gudrun Holland et al. · 2023 · Frontiers in Cellular and Infection Microbiology

Introduction Tularemia is mainly caused by Francisella tularensis ( Ft ) subsp. tularensis ( Ftt ) and Ft subsp. holarctica ( Ftt ) in humans and in more than 200 animal species including rabbits and hares. Human clinical manifestations depend on the route of infection and range from flu-like symptoms to severe pneumonia with a mortality rate up to 60% without treatment. So far, only 2D cell culture and animal models are used to study Francisella virulence , but the gained results are transferable to human infections only to a certain extent. Method In this study, we firstly established an ex

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Anticancer efficacy of the hypoxia‐activated prodrug evofosfamide is enhanced in combination with proapoptotic receptor agonists against osteosarcoma

Vasilios Liapis, Aneta Zysk, Mark DeNichilo et al. · 2017 · Cancer Medicine

Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, hypoxia also leads to treatment opportunities as demonstrated by the development of compounds that target regions of hypoxia within tumors. Evofosfamide is a hypoxia-activated prodrug that is created by linking the hypoxia-seeking 2-nitroimidazole moiety to the cytotoxic bromo-isophosphoramide mustard (Br-IPM). When evofosfamide is delivered to hypoxic regions of tumors, the DNA cross-linking toxin, Br-IPM, is released leading to cell death. This study assessed the anticancer efficacy of evofosfamide in

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

BMI variability and cardiovascular outcomes within clinical trial and real-world environments in type 2 diabetes: an IMI2 SOPHIA study

Robert Massey, Yu Chen, Marina Panova‐Noeva et al. · 2024 · Cardiovascular Diabetology

BACKGROUND: BMI variability has been associated with increased cardiovascular disease risk in individuals with type 2 diabetes, however comparison between clinical studies and real-world observational evidence has been lacking. Furthermore, it is not known whether BMI variability has an effect independent of HbA1c variability. METHODS: We investigated the association between BMI variability and 3P-MACE risk in the Harmony Outcomes trial (n = 9198), and further analysed placebo arms of REWIND (n = 4440) and EMPA-REG OUTCOME (n = 2333) trials, followed by real-world data from the Tayside Bioreso

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Gut microbiome and its metabolites in liver cirrhosis: mechanisms and clinical implications

Luyuan Chang, Yang Liu, Haipeng Li et al. · 2025 · Frontiers in Cellular and Infection Microbiology

Cirrhosis remains a significant global health burden, causing approximately 1.4-1.5 million deaths each year and contributing to nearly 46 million disability-adjusted life years (DALYs) worldwide. Increasing evidence identifies the gut-liver axis as a central driver of disease progression, wherein intestinal dysbiosis, barrier disruption, and microbe-derived metabolites collectively exacerbate inflammation, fibrogenesis, and related complications. Across more than 40 recent studies, gut microbial α-diversity declined by 30-60%, and over 80% reported a marked depletion of short-chain fatty acid

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

A Potential Role of Progestin-Induced Laminin-5/α6-Integrin Signaling in the Formation of Side Branches in the Mammary Gland

Gabriele Meyer, Jeffrey R. Leipprandt, Jianwei Xie et al. · 2012 · Endocrinology

Mammary organoids from adult mice produce tubules, analogous to mammary ducts in vivo, in response to hepatocyte growth factor (HGF) when cultured in collagen gels. The combination of HGF plus progestin (R5020) causes reduced tubule number…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Accurate modeling of replication rates in genome-wide association studies by accounting for Winner’s Curse and study-specific heterogeneity

Jennifer Zou, Jinjing Zhou, Sarah Faller et al. · 2022 · G3 Genes Genomes Genetics

Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with complex human traits, but only a fraction of variants identified in discovery studies achieve significance in replication studies. Replication in genome-wide association studies has been well-studied in the context of Winner's Curse, which is the inflation of effect size estimates for significant variants due to statistical chance. However, Winner's Curse is often not sufficient to explain lack of replication. Another reason why studies fail to replicate is that there are fundamental difference

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Genetic Predictors of Depressive Symptoms in the Look AHEAD Trial

Jeanne M. McCaffery, George D. Papandonatos, Lucy F. Faulconbridge et al. · 2015 · Psychosomatic Medicine

OBJECTIVES: Numerous studies have found elevated depressive symptoms among individuals with Type 2 diabetes, yet the mechanisms remain unclear. We examined whether genetic loci previously associated with depressive symptoms predict…

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Replication FailureOpen accessBiochemistry, Genetics and Molecular Biology

A specific microRNA profile as predictive biomarker for systemic treatment in patients with metastatic colorectal cancer

Dennis Poel, Elske C. Gootjes, Lotte Bakkerus et al. · 2020 · Cancer Medicine

BACKGROUND: Palliative systemic therapy is currently standard of care for patients with extensive metastatic colorectal cancer (mCRC). A biomarker predicting chemotherapy benefit which prevents toxicity from ineffective treatment is urgently needed. Therefore, a previously developed tissue-derived microRNA profile to predict clinical benefit from chemotherapy was evaluated in tissue biopsies and serum from patients with mCRC. METHODS: Samples were prospectively collected from patients (N = 132) who were treated with capecitabine or 5-FU/LV with oxaliplatin ± bevacizumab. Response evaluation wa

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Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology

Increasing imputation and prediction accuracy for Chinese Holsteins using joint Chinese–Nordic reference population

Peipei Ma, Mogens Sandø Lund, Xiangdong Ding et al. · 2014 · Journal of Animal Breeding and Genetics

This study investigated the effect of including Nordic Holsteins in the reference population on the imputation accuracy and prediction accuracy for Chinese Holsteins. The data used in this study include 85 Chinese Holstein bulls genotyped…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Newly Developed Structure-Based Methods Do Not Outperform Standard Sequence-Based Methods for Large-Scale Phylogenomics

Giacomo Mutti, Eduard Ocaña‐Pallarès, Toni Gabaldón · 2025 · Molecular Biology and Evolution

Recent developments in protein structure prediction have allowed the use of this previously limited source of information at genome-wide scales. It has been proposed that the use of structural information may offer advantages over…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Diagnostic challenges in hemangioblastoma: lessons from a rare case presentation

Jayeshkumar Kanani · 2025 · The Egyptian Journal of Neurosurgery : the official publication of the Egyptian Society of Neurological Surgeons/Egyptian journal of neurosurgery

Abstract Background Hemangioblastomas are rare, slow-growing benign neoplasms predominantly affecting the central nervous system (CNS). Despite their benign nature, they pose diagnostic challenges due to their diverse clinical manifestations and radiological features. Case presentation. A 40-year-old male presented with chronic headaches and diplopia persisting for 8 years. Initial MRI revealed two cystic lesions in the cerebellum, causing compression and herniation. Surgical removal of one cyst yielded inconclusive results. Follow-up MRIs showed cyst growth and syrinx development. The patient

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