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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 ReportBiochemistry, Genetics and Molecular Biology

Significant Differences in Capsid Properties and Potency Between Adeno-Associated Virus Vectors Produced in Sf9 and HEK293 Cells

April R. Giles, Martin Lock, Shu‐Jen Chen et al. · 2023 · Human Gene Therapy

For successful vector-based gene therapy manufacturing, the selected adeno-associated virus (AAV) vector production system must produce vector at sufficient scale. However, concerns have arisen regarding the quality of vector produced…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

An unbiased comparison of 14 epigenetic clocks in relation to 174 incident disease outcomes

Christos Mavrommatis, Daniel W. Belsky, Kejun Ying et al. · 2025 · Nature Communications

Epigenetic Clocks have been trained to predict chronological age, healthspan and lifespan. Such clocks are often analysed in relation to disease outcomes - typically using small datasets and a limited number of clocks. Here, we present a large-scale (n = 18,859), unbiased comparison of 14 widely used clocks as predictors of 174 incident disease outcomes and all-cause mortality over 10-years of follow up. Second- and third-generation clocks significantly outperform first-generation clocks, which have limited applications in disease settings. Of the 176 Bonferroni significant (P 1%. However, the

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Significant association between renal function and amyloid-positive area in renal biopsy specimens in AL amyloidosis

Takeshi Kuroda, Naohito Tanabe, Daisuke Kobayashi et al. · 2012 · BMC Nephrology

BACKGROUND: The kidney is a major target organ for systemic amyloidosis that often affects the kidney including proteinura, and elevated serum creatinine (Cr). The correlation between amount of amyloid deposits and clinical parameters is not known. The aim of this study was to clarify correlation the amyloid area in all renal biopsy specimen and clinical parameters. METHODS: Fifty-eight patients with an established diagnosis of AL amyloidosis participated in the study. All patients showed amyloid deposits in renal biopsies. We retrospectively investigated the correlation between clinical data

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Long-term functional and structural outcomes in X-linked retinoschisis: implications for clinical trials

Beau J. Fenner, Jonathan F. Russell, Arlene V. Drack et al. · 2023 · Frontiers in Medicine

Introduction X-linked retinoschisis (XLRS) is an inherited retinal disease (IRD) caused by pathogenic mutations in the retinoschisin gene, RS1 . Affected individuals develop retinal layer separation, leading to loss of visual acuity (VA). Several XLRS gene therapy trials have been attempted but none have met their primary endpoints. An improved understanding of XLRS natural history and clinical outcomes may better inform future trials. Here, we report the long-term functional and structural outcomes of XLRS and the relevance of RS1 genotypes to the visual prognosis of affected individuals. Met

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Comparison of wild-type KT2440 and genome-reduced EM42 Pseudomonas putida strains for muconate production from aromatic compounds and glucose

Caroline R. Amendola, William T. Cordell, Colin M. Kneucker et al. · 2023 · Metabolic Engineering

Pseudomonas putida KT2440 is a robust, aromatic catabolic bacterium that has been widely engineered to convert bio-based and waste-based feedstocks to target products. Towards industrial domestication of P. putida KT2440, rational genome…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Polygenic risk scores in schizophrenia with clinically significant copy number variants

Satoru Taniguchi, Kohei Ninomiya, Itaru Kushima et al. · 2019 · Psychiatry and Clinical Neurosciences

AIMS: Recent studies have revealed that the interplay between polygenic risk scores (PRS) and large copy number variants (CNV; >500kb) is essential for the etiology of schizophrenia (SCZ). To replicate previous findings, including those for smaller CNV (>10kb), the PRS between SCZ patients with and without CNV were compared. METHODS: The PRS were calculated for 724 patients with SCZ and 1178 healthy controls (HC), genotyped using array-based comparative genomic hybridization and single nucleotide polymorphisms chips, and comparisons were made between cases and HC, or between subjects with and

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Chronological age, biological age, and individual variation in the stress response in the European starling: a follow-up study

Annie Gott, Clare Andrews, María Larriva et al. · 2018 · PeerJ

) found that a marker of biological age predicted the strength of the stress response even in individuals of the same chronological age. Specifically, birds that had experienced greater developmental telomere attrition (DTA) showed a lower peak corticosterone (CORT) response to an acute stressor, and more rapid recovery of CORT levels towards baseline. Here, we performed a follow-up study using the same capture-handling-restraint stressor in a separate cohort of starlings that had been subjected to a developmental manipulation of food availability and begging effort. We measured the CORT respo

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Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology

No Significant Effect of 7,8-Dihydroxyflavone on APP Processing and Alzheimer-Associated Phenotypes

Weitao Zhou, Xiaoyong Li, Daochao Huang et al. · 2015 · Current Alzheimer Research

It is reported that 7,8-dihydroxyflavone (DHF), a TrkB agonist, has beneficial effects on neuronal excitotoxicity, stroke, and Parkinson disease in animal models by enhancing axon regeneration, muscle reinnervation and neuromuscular…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Residential Proximity to Major Roadways at Birth, DNA Methylation at Birth and Midchildhood, and Childhood Cognitive Test Scores: Project Viva(Massachusetts, USA)

Cheng Peng, Martijn den Dekker, Andrés Cárdenas et al. · 2018 · Environmental Health Perspectives

BACKGROUND: Epigenetic variability is hypothesized as a regulatory pathway through which prenatal exposures may influence child development and health. OBJECTIVE: We sought to examine the associations of residential proximity to roadways at birth and epigenome-wide DNA methylation. We also assessed associations of differential methylation with child cognitive outcomes. METHODS: We estimated residential proximity to roadways at birth using a geographic information system (GIS) and cord blood methylation using Illumina's HumanMethylation450-array in 482 mother-child pairs in Project Viva. We ide

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Comparison of ambulatory capacity and disease progression of Duchenne muscular dystrophy subjects enrolled in the drisapersen DMD114673 study with a matched natural history cohort of subjects on daily corticosteroids

Nathalie Goemans, M. Tulinius, Anna‐Karin Kroksmark et al. · 2016 · Neuromuscular Disorders

Duchenne muscular dystrophy is a rare genetic disorder with life-limiting pathology. Drisapersen induces exon 51 skipping, thereby producing a shorter but functional dystrophin protein. The longest available data are from an open-label…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Medium-sized protein language models perform well at transfer learning on realistic datasets

Luiz Carlos Vieira, Morgan L. Handojo, Claus O. Wilke · 2025 · Scientific Reports

Protein language models (pLMs) can offer deep insights into evolutionary and structural properties of proteins. While larger models, such as the 15 billion parameter model ESM-2, promise to capture more complex patterns in sequence space, they also present practical challenges due to their high dimensionality and high computational cost. We systematically evaluated the performance of various ESM-style models across multiple biological datasets to assess the impact of model size on transfer learning via feature extraction. Surprisingly, we found that larger models do not necessarily outperform

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

MicroRNA expression profiling predicts clinical outcome of carboplatin/paclitaxel-based therapy in metastatic melanoma treated on the ECOG-ACRIN trial E2603

Liza C. Villaruz, Grace Huang, Marjorie Romkes et al. · 2015 · Clinical Epigenetics

BACKGROUND: Carboplatin/paclitaxel (CP), with or without sorafenib, result in objective response rates of 18-20 % in unselected chemotherapy-naïve patients. Molecular predictors of survival and response to CP-based chemotherapy in metastatic melanoma (MM) are critical to improving the therapeutic index. Intergroup trial E2603 randomized MM patients to CP with or without sorafenib. Expression data were collected from pre-treatment formalin-fixed paraffin-embedded (FFPE) tumor tissues from 115 of 823 patients enrolled on E2603. The selected patients were balanced across treatment arms, BRAF stat

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Genetic polymorphisms of the adrenergic system and implantable cardioverter-defibrillator therapies in patients with heart failure

Diego Chemello, Luís Eduardo Paim Rohde, Kátia Gonçalves dos Santos et al. · 2010 · EP Europace

AIMS: We investigated whether the combination of beta(1)-Gly389Arg and GNB3 C825T, two genetic polymorphisms strictly related to adrenergic system modulation, could act as predictors of appropriate therapies in patients with heart failure…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Retina-directed gene therapy: Achievements and remaining challenges

Josef Biber, Catharina Gandor, Elvir Bećirović et al. · 2025 · Pharmacology & Therapeutics

Gene therapy is an innovative medical approach that offers new treatment options for congenital and acquired diseases by transferring, correcting, inactivating or regulating genes to supplement, replace or modify a gene function. The approval of voretigene neparvovec (Luxturna), a gene therapy for RPE65-associated retinopathy, has marked a milestone for the field of retinal gene therapy, but has also helped to accelerate the development of gene therapies for genetic diseases affecting other organs. Voretigene neparvovec is a vector based on adeno-associated virus (AAV) that delivers a function

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Amino Acid Residues 489–503 of Dihydropyridine Receptor (DHPR) β1a Subunit Are Critical for Structural Communication between the Skeletal Muscle DHPR Complex and Type 1 Ryanodine Receptor

José M. Eltit, Clara Franzini‐Armstrong, Claudio F. Pérez · 2014 · Journal of Biological Chemistry

The β1a subunit is a cytoplasmic component of the dihydropyridine receptor (DHPR) complex that plays an essential role in skeletal muscle excitation-contraction (EC) coupling. Here we investigate the role of the C-terminal end of this auxiliary subunit in the functional and structural communication between the DHPR and the Ca2+ release channel (RyR1). Progressive truncation of the β1a C terminus showed that deletion of amino acid residues Gln489 to Trp503 resulted in a loss of depolarization-induced Ca2+ release, a severe reduction of L-type Ca2+ currents, and a lack of tetrad formation as eva

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Metabolic and immune crosstalk between cancer-associated fibroblasts and pancreatic cancer cells

Qiyao Zhang, Zhen Cao, Shangcheng Yan et al. · 2025 · Journal of Translational Medicine

Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), is notorious for its aggressive nature and dismal prognosis, ranking as a leading cause of cancer-related mortality worldwide. Despite advancements in surgical…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Targeting mitochondrial transporters and metabolic reprogramming for disease treatment

Mboneye Anselme, Huafeng He, Chengyang Lai et al. · 2025 · Journal of Translational Medicine

In the realm of cellular biochemistry, mitochondria have been increasingly recognized for their critical role in both cellular metabolism and the etiology of various diseases. Mitochondrial transporters (MTs) are essential for maintaining…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

MLH1 Region Polymorphisms Show a Significant Association with CpG Island Shore Methylation in a Large Cohort of Healthy Individuals

Andrea J. Savio, Mathieu Lemire, Miralem Mrkonjic et al. · 2012 · PLoS ONE

Single nucleotide polymorphisms (SNPs) are the most common form of genetic variation. We previously demonstrated that SNPs (rs1800734, rs749072, and rs13098279) in the MLH1 gene region are associated with MLH1 promoter island methylation, loss of MLH1 protein expression, and microsatellite instability (MSI) in colorectal cancer (CRC) patients. Recent studies have identified less CpG-dense "shore" regions flanking many CpG islands. These shores often exhibit distinct methylation profiles between different tissues and matched normal versus tumor cells of patients. To date, most epigenetic studie

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Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology

ASSA: Fast identification of statistically significant interactions between long RNAs

Ivan Antonov, Andrey V. Marakhonov, Maria A. Zamkova et al. · 2018 · Journal of Bioinformatics and Computational Biology

The discovery of thousands of long noncoding RNAs (lncRNAs) in mammals raises a question about their functionality. It has been shown that some of them are involved in post-transcriptional regulation of other RNAs and form inter-molecular…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Heritability and Genome-Wide Association Analyses of Human Gait Suggest Contribution of Common Variants

Hieab H.H. Adams, Vincentius J.A. Verlinden, Michele L. Callisaya et al. · 2015 · The Journals of Gerontology Series A

Human gait is a complex neurological and musculoskeletal function, of which the genetic basis remains largely unknown. To determine the influence of common genetic variants on gait parameters, we studied 2,946 participants of the Rotterdam…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Molecular mechanisms underlying the lifespan and healthspan benefits of dietary restriction across species

Jialin Fan, Yunpeng Xu · 2026 · Frontiers in Genetics

Dietary restriction (DR), defined as reduced caloric intake or selective limitation of specific nutrients without malnutrition, is one of the most robust interventions known to extend lifespan and healthspan across species. Studies from yeast to mammals demonstrate that DR elicits conserved genetic, transcriptional, and epigenetic programs that promote cellular maintenance and stress resistance. At the molecular level, DR engages evolutionarily conserved nutrient-sensing pathways, including insulin/IGF-1 signaling (IIS), the mechanistic target of rapamycin (mTOR), AMP-activated protein kinase

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies

Enrique Rozengurt, G. Eibl · 2026 · Signal Transduction and Targeted Therapy

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease for which there is no effective treatment. A deep understanding of the mechanisms underlying the molecular pathogenesis, signaling pathways and risk factors leading to PDAC is of paramount importance for identifying novel targets, prognostic markers, preventive strategies, and signature markers for use in specific and personalized therapeutic procedures. Activating somatic mutations in the KRAS oncogene play a critical role in PDAC initiation and maintenance. Here, we highlight the complex interplay between KRAS signaling, the tr

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Analysis of Genome-Wide Association Study (GWAS) data looking for replicating signals in Alzheimer's disease (AD).

Hui Shi, Christopher Medway, James M. Bullock et al. · 2010 · PubMed

We have performed cross-platform comparisons of output from 4 GWAS in late-onset Alzheimer's disease (LOAD) - Reiman et al., 2007; Li et al., 2008; Beecham et al., 2008 and Carrasquillo et al., 2009 to search for new association signals.…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Clonal diploid and autopolyploid breeding strategies to harness heterosis: insights from stochastic simulation

Marlee R. Labroo, Jeffrey B. Endelman, Dorcus C. Gemenet et al. · 2023 · Theoretical and Applied Genetics

KEY MESSAGE: Reciprocal recurrent selection sometimes increases genetic gain per unit cost in clonal diploids with heterosis due to dominance, but it typically does not benefit autopolyploids. Breeding can change the dominance as well as additive genetic value of populations, thus utilizing heterosis. A common hybrid breeding strategy is reciprocal recurrent selection (RRS), in which parents of hybrids are typically recycled within pools based on general combining ability. However, the relative performances of RRS and other breeding strategies have not been thoroughly compared. RRS can have re

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Stride Velocity 95 th Centile Detects Decline in Ambulatory Function Over Shorter Intervals than the 6-Minute Walk Test or North Star Ambulatory Assessment in Duchenne Muscular Dystrophy

Michael Rabbia, Maitea Guridi Ormazabal, Hannah Staunton et al. · 2024 · Journal of Neuromuscular Diseases

Background: Stride Velocity 95th Centile (SV95C) is the first wearable device-derived clinical outcome assessment (COA) to receive European Medicines Agency (EMA) qualification as a primary endpoint in ambulant patients with Duchenne muscular dystrophy (DMD) aged ≥4 years. Objective: To compare SV95C-in its first-ever clinical trial application as a secondary endpoint-with established motor function COAs used in the trial (Four-Stair Climb [4SC] velocity, North Star Ambulatory Assessment [NSAA], and Six-Minute Walk Distance [6MWD]). Methods: SV95C was a secondary endpoint in a subset (n = 47)

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Diabetes and Pancreatic Cancer

Burney, Saira, Muhammad Wasif Saif, Saif, Muhammad Wasif et al. · 2013 · PubMed

CONTEXT: Pancreatic cancer is the fourth leading cause of cancer mortality in the United States. Most of the patients are diagnosed in the metastatic staging. Consolidated risk factors include chronic pancreatitis, smoking and family…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

APC promoter is frequently methylated in pancreatic juice of patients with pancreatic carcinomas or periampullary tumors

Mireia M. Ginesta, Zamira V. Díaz‐Riascos, Juli Busquets et al. · 2016 · Oncology Letters

Early detection of pancreatic and periampullary neoplasms is critical to improve their clinical outcome. The present authors previously demonstrated that DNA hypermethylation of adenomatous polyposis coli (APC), histamine receptor H2…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Multi-modality artificial intelligence-based transthyretin amyloid cardiomyopathy detection in patients with severe aortic stenosis

Isaac Shiri, Sebastian Balzer, Giovanni Baj et al. · 2024 · European Journal of Nuclear Medicine and Molecular Imaging

PURPOSE: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a frequent concomitant condition in patients with severe aortic stenosis (AS), yet it often remains undetected. This study aims to comprehensively evaluate artificial intelligence-based models developed based on preprocedural and routinely collected data to detect ATTR-CM in patients with severe AS planned for transcatheter aortic valve implantation (TAVI). METHODS: Tc]-DPD) for the presence of ATTR-CM. Clinical, laboratory, electrocardiogram, echocardiography, invasive measurements, 4-dimensional cardiac CT (4D-CCT) strain data, and C

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Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology

Significant differences in dietary intake of NCAA Division III soccer players compared to recommended levels

Kaneen Gomez-Hixson, Ericka Biagioni, Melissa Brown · 2020 · Journal of American College Health

Objective: This study evaluated dietary intake patterns of NCAA Division III soccer players compared to recommended levels. Participants: NCAA Division III soccer players (n = 75). Methods: Actual dietary intake was determined by the…

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