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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

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

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

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

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

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

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

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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

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Integrating single-cell RNA-seq datasets with substantial batch effects

Karin Hrovatin, Amir Ali Moinfar, Luke Zappia et al. · 2025 · BMC Genomics

Integration of single-cell RNA-sequencing (scRNA-seq) datasets is standard in scRNA-seq analysis. Nevertheless, current computational methods struggle to harmonize datasets across systems such as species, organoids and primary tissue, or different scRNA-seq protocols, including single-cell and single-nuclei. Conditional variational autoencoders (cVAE) are a popular integration method, however, existing strategies for stronger batch correction have limitations. Increasing the Kullback-Leibler divergence regularization does not improve integration and adversarial learning removes biological sign

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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…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Spatial transcriptomics reveals influence of microenvironment on intrinsic fates in melanoma therapy resistance

Ryan H. Boe, Catherine G. Triandafillou, Rossana Lazcano et al. · 2026 · Genome biology

Abstract Resistance to cancer therapy is driven by both cell-intrinsic and microenvironmental factors. We use spatial transcriptomics and single-cell RNA sequencing to uncover distinct resistance programs in melanoma cells shaped by intrinsic cellular states and the tumor microenvironment. Consensus non-negative matrix factorization reveals shared intrinsic resistance programs across cell lines. In patient samples, these resistance programs coexist within individual tumors and associate with diverse immune signatures. Single-cell resolution spatial transcriptomics in xenograft models reveals b

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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 ReportOpen accessBiochemistry, Genetics and Molecular Biology

Dynamics of natural selection preceding human viral epidemics and pandemics

Jennifer L. Havens, Sergei L. Kosakovsky Pond, Jordan D. Zehr et al. · 2026 · Cell

Using a phylogenetic framework to characterize natural selection, we investigate the hypothesis that zoonotic viruses require adaptation prior to zoonosis to sustain human-to-human transmission. Examining the zoonotic emergence of Ebola…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Enhanced Electrochemiluminescence by Nanocatalyst-Supported Nanochannel–Surfactant Micelle Assembly for Ultrasensitive Detection of Rifampicin

Jiahui Lin, Zhongping Mao, Fei Yan · 2026 · Biosensors

Developing an ultrasensitive electrochemiluminescence (ECL) detection platform remains challenging due to the limited enrichment efficiency of ECL emitters and co-reactants at the electrode interface, as well as the insufficient catalytic enhancement of co-reactant conversion. Moreover, simultaneous in situ analyte enrichment and efficient anti-interference capability are often difficult to achieve in a single sensing interface. Herein, a new ECL platform was developed based on nanocatalyst-supported nanochannel-confined surfactant micelle (SM) system, which integrates an enhanced luminol-diss

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Synthesis and multilevel evaluation of benzimidazole-based anticancer compounds: DNA/serum albumin interaction, and in-depth theoretical insights

Sevgi Kundu, Senem Akkoç, Yalçın Erzurumlu et al. · 2026 · Molecular and Cellular Biochemistry

Abstract Within the scope of this investigation, two novel compounds ( 3a and 3b ) were designed and synthesized in two steps. Compounds 3a and 3b were tested utilizing the MTT study to evaluate their in vitro cytotoxic activity against healthy human embryonic kidney, lung cancer, breast cancer, and human liver cancer cell lines. It was determined that compound 3b exhibited high levels of cytotoxic activity against both liver and breast cancer cell lines, with IC 50 values of 10.83 and 11.55 µM, respectively. Also, to elucidate the anticancer mechanism of compounds, pro-apoptotic BAX and BiD ,

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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

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

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Cell-free DNA in sepsis: from molecular insights to clinical management

Lei Li, Hongchao Huang, Yin He et al. · 2025 · Military Medical Research

Sepsis is a dysregulated host response to infection that frequently results in fatal multiple organ dysfunction. Despite advances in clinical identification and management, both its incidence and mortality have remained persistently high. Emerging evidence indicates that cell-free DNA (cfDNA), as a novel biomarker and molecular therapeutic target, holds promise for improving the clinical management of sepsis. cfDNA refers to DNA fragments present in body fluids, including naked DNA, membrane-coated DNA, nucleosomes, and neutrophil extracellular traps (NETs). cfDNA is released from host cells o

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Modulation in Growth, Yield, Water Relations, and Mineral Nutrients of Canola ( Brassica napus L.) by Foliar Application of Melatonin and Ascorbic Acid Under Salinity Stress

Tahrim Ramzan, Muhammad Shahbaz, Farooq Ahmad et al. · 2026 · New Zealand Journal of Crop and Horticultural Science

Salinity stress is a major abiotic factor that inhibits plant growth and yield. This study's objective was to evaluate how foliar applications of melatonin and ascorbic acid affected canola varieties under salt stress. The treatments of…

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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

Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries

Alicia Huerta‐Chagoya, Joohyun Kim, Ravi Mandla et al. · 2026 · The Lancet Diabetes & Endocrinology

BACKGROUND: Polygenic risk scores (PRSs) improve prediction of the development of type 2 diabetes over the use of clinical risk factors alone; however, they perform poorly in populations of non-European ancestry, limiting their global…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Decaying and expanding Erk gradients process memory of skeletal size during zebrafish fin regeneration

Ashley Rich, Ziqi Li, Alessandro De Simone et al. · 2026 · Nature Physics

Amputated salamander limbs or fish fins precisely regenerate to their pre-injury size, providing a paradigm for positional memory. Although this phenomenon has been appreciated for centuries, how position-dependent cues control tissue…

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Replication FailureBiochemistry, Genetics and Molecular Biology

Identification of Statistically Significant Features from Random Forests

Jérôme Paul, Michel Verleysen, Pierre Dupont · 2013

Abstract. Embedded feature selection can be performed by analyzing the variables used in a Random Forest. Such a multivariate selection takes into account the interactions between variables but is not easy to interpret in a statistical…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

The extracellular matrix in inflammation and cancer

Wanting Zhang, Yuhang Xiang, Chen Lu et al. · 2026 · Molecular Biomedicine

The extracellular matrix (ECM) forms a dynamic structure around cells, providing environmental cues, mechanical support, and tissue protection. It is composed of fibrous proteins, glycosaminoglycans (GAGs), proteoglycans, and glycoproteins. The molecular, physical, and mechanical properties of the ECM regulate the motility, survival, and function of immune cells. In most cancers, inflammatory cytokines and proteases-particularly matrix metalloproteinases(MMPs)-released within the immune-infiltrated inflammatory microenvironment can remodel the ECM. Cytokines such as tumor necrosis factor-α (TN

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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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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial

Richard E. Pratley, Douglas Scott Denham, Rupal Trivedi et al. · 2026 · Nature Medicine

Abstract Loss of lean mass in proportion to total weight loss is observed with incretin mimetic therapies such as tirzepatide and has the potential to adversely affect health and function. Apitegromab is an investigational, fully human monoclonal antibody that selectively inhibits myostatin activation and is, thereby, capable of increasing muscle mass. In the randomized, double-blind, placebo-controlled phase 2 EMBRAZE study, adults with overweight or obesity ( n = 102) were randomized 1:1 to receive tirzepatide plus apitegromab (10 mg kg −1 ) or tirzepatide plus placebo. At week 24, apitegrom

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

A randomized phase II/III study of paclitaxel/carboplatin/metformin versus paclitaxel/carboplatin/placebo as initial therapy for measurable stage III or IVA, stage IVB, or recurrent endometrial cancer: An NRG oncology/GOG study

Victoria Bae‐Jump, Michael W. Sill, Paola A. Gehrig et al. · 2025 · Gynecologic Oncology

INTRODUCTION: We evaluated the efficacy of the addition of the anti-diabetic drug metformin to standard-of-care paclitaxel and carboplatin (PC) in patients with advanced and recurrent endometrial cancer (EC). METHODS: In this phase II/III…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Lactylation as a metabolic-epigenetic switch in cancer: dual roles in cell death resistance and therapeutic vulnerability

Chengjiao Yang, Ruici Yang, Binbin Zheng et al. · 2026 · Cell Death and Disease

Protein lactylation emerges as a pivotal metabolic rheostat, translating microenvironmental lactate flux into stable programs that orchestrate cancer treatment resistance. This review synthesizes recent advances under the framework of "Lactylation Switch in Cancer Vulnerabilities." We dissect the dominant enzymatic pathways (AARS1/2, KATs, HDACs) and non-enzymatic mechanisms (MGO/LGSH), alongside their critical structural underpinnings. Furthermore, we delineate how lactylation signals are interpreted by specific readers (e.g., TRIM33), directly reprogram non-histone protein function through s

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Oestradiol and reproductive outcomes in ART: when too much of a good thing hurts

Mathilde Bourdon, Chloé Maignien, Marion Ouazana et al. · 2025 · Reproductive BioMedicine Online

Oestradiol plays a crucial role in reproduction, particularly in assisted reproductive technology (ART), where it can reach supraphysiological concentrations. These fluctuations occur during ovarian stimulation in fresh embryo transfer cycles and during endometrial preparation for frozen embryo transfer, potentially impacting implantation and perinatal outcomes. Oestradiol influences endometrial proliferation, receptivity, implantation and placentation, with the sensitivity of the endometrium to systemic oestrogen emerging as a key determinant of reproductive success. In fresh embryo transfer

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