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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

Pairwise comparisons across species are problematic when analyzing functional genomic data

Casey W. Dunn, Felipe Zapata, Catriona Munro et al. · 2018 · Proceedings of the National Academy of Sciences

There is considerable interest in comparing functional genomic data across species. One goal of such work is to provide an integrated understanding of genome and phenotype evolution. Most comparative functional genomic studies have relied…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Do Neonatal Mouse Hearts Regenerate following Heart Apex Resection?

Ditte Caroline Andersen, Suganya Ganesalingam, Charlotte Harken Jensen et al. · 2014 · Stem Cell Reports

The mammalian heart has generally been considered nonregenerative, but recent progress suggests that neonatal mouse hearts have a genuine capacity to regenerate following apex resection (AR). However, in this study, we performed AR or sham…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Genome‐wide analysis of adolescent psychotic‐like experiences shows genetic overlap with psychiatric disorders

Oliver Pain, Frank Dudbridge, Alastair G. Cardno et al. · 2018 · American Journal of Medical Genetics Part B Neuropsychiatric Genetics

This study aimed to test for overlap in genetic influences between psychotic-like experience traits shown by adolescents in the community, and clinically-recognized psychiatric disorders in adulthood, specifically schizophrenia, bipolar disorder, and major depression. The full spectra of psychotic-like experience domains, both in terms of their severity and type (positive, cognitive, and negative), were assessed using self- and parent-ratings in three European community samples aged 15-19 years (Final N incl. siblings = 6,297-10,098). A mega-genome-wide association study (mega-GWAS) for each p

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Single nucleotide polymorphisms associated with non-contact soft tissue injuries in elite professional soccer players: influence on degree of injury and recovery time

Ricard Pruna, Rosa Artells, Jordi Ribas et al. · 2013 · BMC Musculoskeletal Disorders

BACKGROUND: The biological mechanisms involved in non-contact musculoskeletal soft tissue injuries (NCMSTI) are poorly understood. Genetic risk factors may be associated with susceptibility to injuries, and may exert marked influence on recovery times. METHODS: Data on type and degree of injury and recovery time were collected in 73 male professional soccer players (43 White, 11 Black Africans and 19 Hispanics) who suffered total of 242 injuries (203 muscle, 24 ligament, and 15 tendon injuries). One single nucleotide polymorphism (SNPs) in the following genes were analyzed: Elastin (ELN); Titi

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Phase II evaluation of anti-MAdCAM antibody PF-00547659 in the treatment of Crohn’s disease: report of the OPERA study

William J. Sandborn, Scott D. Lee, Dino Tarabar et al. · 2017 · Gut

Objective This phase II, randomised, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of PF-00547659, a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

The performance of the Congruence Among Distance Matrices (CADM) test in phylogenetic analysis

Véronique Campbell, Pierre Legendre, François-Joseph Lapointe · 2011 · BMC Evolutionary Biology

BACKGROUND: CADM is a statistical test used to estimate the level of Congruence Among Distance Matrices. It has been shown in previous studies to have a correct rate of type I error and good power when applied to dissimilarity matrices and to ultrametric distance matrices. Contrary to most other tests of incongruence used in phylogenetic analysis, the null hypothesis of the CADM test assumes complete incongruence of the phylogenetic trees instead of congruence. In this study, we performed computer simulations to assess the type I error rate and power of the test. It was applied to additive dis

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Replication FailureOpen accessBiochemistry, Genetics and Molecular Biology

An epigenome-wide association study in whole blood of measures of adiposity among Ghanaians: the RODAM study

Karlijn Meeks, Peter Henneman, Andrea Venema et al. · 2017 · Clinical Epigenetics

Epigenome-wide association studies (EWAS) have identified DNA methylation loci involved in adiposity. However, EWAS on adiposity in sub-Saharan Africans are lacking despite the high burden of adiposity among African populations. We undertook an EWAS for anthropometric indices of adiposity among Ghanaians aiming to identify DNA methylation loci that are significantly associated. The Illumina 450k DNA methylation array was used to profile DNA methylation in whole blood samples of 547 Ghanaians from the Research on Obesity and Diabetes among African Migrants (RODAM) study. Differentially methylat

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Unfolded Protein Response in Cancer: IRE1α Inhibition by Selective Kinase Ligands Does Not Impair Tumor Cell Viability

Paul E. Harrington, Kaustav Biswas, David J. Malwitz et al. · 2014 · ACS Medicinal Chemistry Letters

The kinase/endonuclease inositol requiring enzyme 1 (IRE1α), one of the sensors of unfolded protein accumulation in the endoplasmic reticulum that triggers the unfolded protein response (UPR), has been investigated as an anticancer target.…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer

Miguel Martín, Aleix Prat, Álvaro Rodríguez-Lescure et al. · 2013 · Breast Cancer Research and Treatment

To identify a group of patients who might benefit from the addition of weekly paclitaxel to conventional anthracycline-containing chemotherapy as adjuvant therapy of node-positive operable breast cancer. The predictive value of PAM50…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Population Genetic Analyses of the Fungal Pathogen Colletotrichum fructicola on Tea-Oil Trees in China

Li He, Guoying Zhou, Junang Liu et al. · 2016 · PLoS ONE

The filamentous fungus Colletotrichum fructicola is found in all five continents and is capable of causing severe diseases in a number of economically important plants such as avocado, fig, cocoa, pear, and tea-oil trees. However, almost nothing is known about its patterns of genetic variation and epidemiology on any of its host plant species. Here we analyzed 167 isolates of C. fructicola obtained from the leaves of tea-oil tree Camellia oleifera at 15 plantations in seven Chinese provinces. Multilocus sequence typing was conducted for all isolates based on DNA sequences at fragments of four

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Age and gender effects on DNA strand break repair in peripheral blood mononuclear cells

Christian Garm, María Moreno‐Villanueva, Alexander Bürkle et al. · 2012 · Aging Cell

Exogenous and endogenous damage to DNA is constantly challenging the stability of our genome. This DNA damage increase the frequency of errors in DNA replication, thus causing point mutations or chromosomal rearrangements and has been…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Mitochondrial DNA heteroplasmy in diabetes and normal adults: role of acquired and inherited mutational patterns in twins

Gal Avital, Mor Buchshtav, Ilia Zhidkov et al. · 2012 · Human Molecular Genetics

Heteroplasmy, the mixture of mitochondrial genomes (mtDNA), varies among individuals and cells. Heteroplasmy levels alter the penetrance of pathological mtDNA mutations, and the susceptibility to age-related diseases such as Parkinson's…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Comprehensive assessment of multiple biases in small RNA sequencing reveals significant differences in the performance of widely used methods

Carrie Wright, Anandita Rajpurohit, Emily E. Burke et al. · 2019 · BMC Genomics

BACKGROUND: RNA sequencing offers advantages over other quantification methods for microRNA (miRNA), yet numerous biases make reliable quantification challenging. Previous evaluations of these biases have focused on adapter ligation bias with limited evaluation of reverse transcription bias or amplification bias. Furthermore, evaluations of the quantification of isomiRs (miRNA isoforms) or the influence of starting amount on performance have been very limited. No study had yet evaluated the quantification of isomiRs of altered length or compared the consistency of results derived from multiple

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Improving natural product research translation: From source to clinical trial

Barbara C. Sorkin, Adam J. Kuszak, Gregory Bloss et al. · 2019 · The FASEB Journal

While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Statins inhibit tumor progression via an enhancer of zeste homolog 2‐mediated epigenetic alteration in colorectal cancer

Satoshi Ishikawa, Hiromitsu Hayashi, Kouichi Kinoshita et al. · 2013 · International Journal of Cancer

While statin intake has been proven to reduce the risk of colorectal cancer (CRC), the mechanism of antitumor effects and clinical significance in survival benefits remain unclear. Statin-induced antiproliferative effects and its…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Addition of Metformin to Concurrent Chemoradiation in Patients With Locally Advanced Non–Small Cell Lung Cancer

Heath D. Skinner, Chen Hu, Theodoros Tsakiridis et al. · 2021 · JAMA Oncology

IMPORTANCE: Non-small cell lung cancer (NSCLC) has relatively poor outcomes. Metformin has significant data supporting its use as an antineoplastic agent. OBJECTIVE: To compare chemoradiation alone vs chemoradiation and metformin in stage…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Genome-wide association of anthropometric traits in African- and African-derived populations

Seung Joo Kang, Charleston W. K. Chiang, C. D. Palmer et al. · 2010 · Human Molecular Genetics

Genome-wide association (GWA) studies have identified common variants that are associated with a variety of traits and diseases, but most studies have been performed in European-derived populations. Here, we describe the first genome-wide…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Cefiderocol-Based Combination Therapy for “Difficult-to-Treat” Gram-Negative Severe Infections: Real-Life Case Series and Future Perspectives

Davide Fiore Bavaro, Alessandra Belati, Lucia Diella et al. · 2021 · Antibiotics

Cefiderocol is a new cephalosporin displaying against extensively resistant (XDR) Gram-negative bacteria. We report our experience with cefiderocol-based combination therapies as “rescue” treatments in immunocompromised or critically ill patients or in patients with post-surgical infections who had failed previous regimens. A total of 13 patients were treated from 1 September 2020 to 31 March 2021. In total, 5/13 (38%) patients were classified as critically ill, due to severe COVID-19 lung failure; 4/13 (31%) patients had post-surgical infections and 4/13 (31%) had severe infections in immunoc

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Dendrimer-mediated delivery of N-acetyl cysteine to microglia in a mouse model of Rett syndrome

Elizabeth Nance, Siva P. Kambhampati, Elizabeth S. Smith et al. · 2017 · Journal of Neuroinflammation

Rett syndrome (RTT) is a pervasive developmental disorder that is progressive and has no effective cure. Immune dysregulation, oxidative stress, and excess glutamate in the brain mediated by glial dysfunction have been implicated in the pathogenesis and worsening of symptoms of RTT. In this study, we investigated a new nanotherapeutic approach to target glia for attenuation of brain inflammation/injury both in vitro and in vivo using a Mecp2-null mouse model of Rett syndrome. To determine whether inflammation and immune dysregulation were potential targets for dendrimer-based therapeutics in R

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Overcoming natural replication barriers: differential helicase requirements

R. Anand, Kartik Shah, Hengyao Niu et al. · 2011 · Nucleic Acids Research

DNA sequences that form secondary structures or bind protein complexes are known barriers to replication and potential inducers of genome instability. In order to determine which helicases facilitate DNA replication across these barriers,…

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Failed Experiment ReportOpen accessBiochemistry, Genetics and Molecular Biology

Genetic effects influencing risk for major depressive disorder in China and Europe

Tim B. Bigdeli, Stephan Ripke, Roseann E. Peterson et al. · 2017 · Translational Psychiatry

Abstract Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30–40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying c

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Genome-Wide Association Study of Personality Traits in the Long Life Family Study

Harold Bae, Paola Sebastiani, Jenny X. Sun et al. · 2013 · Frontiers in Genetics

Personality traits have been shown to be associated with longevity and healthy aging. In order to discover novel genetic modifiers associated with personality traits as related with longevity, we performed a genome-wide association study (GWAS) on personality factors assessed by NEO-five-factor inventory in individuals enrolled in the Long Life Family Study (LLFS), a study of 583 families (N up to 4595) with clustering for longevity in the United States and Denmark. Three SNPs, in almost perfect LD, associated with agreeableness reached genome-wide significance (p < 10(-8)) and replicated in a

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

A Genome-Wide Association Study of Neuroticism in a Population-Based Sample

Federico C. F. Calboli, Federica Tozzi, N. W. Galwey et al. · 2010 · PLoS ONE

Neuroticism is a moderately heritable personality trait considered to be a risk factor for developing major depression, anxiety disorders and dementia. We performed a genome-wide association study in 2,235 participants drawn from a population-based study of neuroticism, making this the largest association study for neuroticism to date. Neuroticism was measured by the Eysenck Personality Questionnaire. After Quality Control, we analysed 430,000 autosomal SNPs together with an additional 1.2 million SNPs imputed with high quality from the Hap Map CEU samples. We found a very small effect of popu

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

What Can We Learn From Clinical Trials of Exon Skipping for DMD?

Qilong Lu, Sebahattin Çirak, Terence A. Partridge · 2014 · Molecular Therapy — Nucleic Acids

On 20 September 2013, GlaxoSmithKline (GSK) and Prosensa announced that GSK's Phase III clinical trial (NCT01254019) of Drisapersen, an exon skipping drug for Duchenne muscular dystrophy (DMD), failed to meet the primary endpoint of a…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Copy Number Variation in Familial Parkinson Disease

Nathan Pankratz, Alexandra Dumitriu, Kurt N. Hetrick et al. · 2011 · PLoS ONE

Copy number variants (CNVs) are known to cause Mendelian forms of Parkinson disease (PD), most notably in SNCA and PARK2. PARK2 has a recessive mode of inheritance; however, recent evidence demonstrates that a single CNV in PARK2 (but not a single missense mutation) may increase risk for PD. We recently performed a genome-wide association study for PD that excluded individuals known to have either a LRRK2 mutation or two PARK2 mutations. Data from the Illumina370Duo arrays were re-clustered using only white individuals with high quality intensity data, and CNV calls were made using two algorit

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Inhibition of the NOD-Like Receptor Protein 3 Inflammasome Is Protective in Juvenile Influenza A Virus Infection

Bria M. Coates, Kelly L. Staricha, Nandini Ravindran et al. · 2017 · Frontiers in Immunology

Influenza A virus (IAV) is a significant cause of life-threatening lower respiratory tract infections in children. Antiviral therapy is the mainstay of treatment, but its effectiveness in this age group has been questioned. In addition, damage inflicted on the lungs by the immune response to the virus may be as important to the development of severe lung injury during IAV infection as the cytotoxic effects of the virus itself. A crucial step in the immune response to IAV is activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and the subsequent secretion of the inflammatory cytok

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Bubble-chip analysis of human origin distributions demonstrates on a genomic scale significant clustering into zones and significant association with transcription

Larry D. Mesner, Veena Valsakumar, Neerja Karnani et al. · 2010 · Genome Research

We have used a novel bubble-trapping procedure to construct nearly pure and comprehensive human origin libraries from early S- and log-phase HeLa cells, and from log-phase GM06990, a karyotypically normal lymphoblastoid cell line. When…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Evidence for non-colligative function of small cryoprotectants in a freeze-tolerant insect

Jantina Toxopeus, Vladimı́r Košťál, Brent J. Sinclair · 2019 · Proceedings of the Royal Society B Biological Sciences

Freeze tolerance, the ability to survive internal ice formation, facilitates survival of some insects in cold habitats. Low-molecular-weight cryoprotectants such as sugars, polyols and amino acids are hypothesized to facilitate freeze…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Randomised clinical trial: individualised vs. weight‐based dosing of azathioprine in Crohn's disease

T. Dassopoulos, Marla C. Dubinsky, J. L. Bentsen et al. · 2013 · Alimentary Pharmacology & Therapeutics

BACKGROUND: Azathioprine (AZA), a pro-drug metabolised to the active metabolites 6-tioguanine nucleotides (6TGN), is a steroid-sparing therapy for Crohn's disease (CD). AIM: To investigate whether AZA therapy is optimised by individualised…

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Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology

Pregnancy outcomes in women with Familial Mediterranean Fever receiving colchicine: Is amniocentesis justified?

Eli Ben‐Chetrit, Avraham Ben‐Chetrit, Yackov Berkun et al. · 2010 · Arthritis Care & Research

OBJECTIVE: To evaluate the outcome of pregnancies in women with familial Mediterranean fever (FMF) who are taking colchicine, and to reconsider the justification for amniocentesis in these women. METHODS: The outcome of 179 pregnancies in…

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