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Browse the failure-mode index

12,231 real negative results, null findings, and replication failures in Medicine. 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 accessMedicine

Human metapneumovirus infection of organoid-derived human bronchial epithelium represents cell tropism and cytopathology as observed in in vivo models

Pau Ribó-Molina, Stefan van Nieuwkoop, Anna Z. Mykytyn et al. · 2024 · mSphere

ABSTRACT Human metapneumovirus (HMPV), a member of the Pneumoviridae family, causes upper and lower respiratory tract infections in humans. In vitro studies with HMPV have mostly been performed in monolayers of undifferentiated epithelial cells. In vivo studies in cynomolgus macaques and cotton rats have shown that ciliated epithelial cells are the main target of HMPV infection, but these observations cannot be studied in monolayer systems. Here, we established an organoid-derived bronchial culture model that allows physiologically relevant studies on HMPV. Inoculation with multiple prototype

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Negative / Null Result ReportOpen accessMedicine

Lack of significant association between serum inflammatory cytokine profiles and the presence of colorectal adenoma

Curtis J. Henry, Rebecca L. Sedjo, Andrii I. Rozhok et al. · 2015 · BMC Cancer

BACKGROUND: Inflammatory cytokines in the colonic microenvironment have been shown to increase with advance colorectal cancer disease state. However, the contribution of inflammatory cytokines to pre-malignant disease, such as the formation of adenomas, is unclear. METHODS: Using the Milliplex® MAP Human Cytokine/ Chemokine Magnetic Bead Panel Immunoassay, serum cytokine and chemokine profiles were assayed among participants without an adenoma (n = 97) and those with an adenoma (n = 97) enrolled in the NCI-funded Insulin Resistance Atherosclerosis Colon Study. The concentrations of interleukin

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Negative / Null Result ReportOpen accessMedicine

Mutations in the Neuraminidase-Like Protein of Bat Influenza H18N11 Virus Enhance Virus Replication in Mammalian Cells, Mice, and Ferrets

Gongxun Zhong, Shufang Fan, Masato Hatta et al. · 2019 · Journal of Virology

Bats are reservoirs for several severe zoonotic pathogens. The genomes of influenza A viruses of the H17N10 and H18N11 subtypes have been identified in bats, but no live virus has been isolated. The characterization of artificially…

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Negative / Null Result ReportOpen accessMedicine

Forced expression of miR-143 and -145 in cardiomyocytes induces cardiomyopathy with a reductive redox shift

Kota Ogawa, Akiko Noda, Jun Ueda et al. · 2020 · Cellular & Molecular Biology Letters

BACKGROUND: Animal model studies show that reductive stress is involved in cardiomyopathy and myopathy, but the exact physiological relevance remains unknown. In addition, the microRNAs miR-143 and miR-145 have been shown to be upregulated in cardiac diseases, but the underlying mechanisms associated with these regulators have yet to be explored. METHODS: We developed transgenic mouse lines expressing exogenous miR-143 and miR-145 under the control of the alpha-myosin heavy chain (αMHC) promoter/enhancer. RESULTS: The two transgenic lines showed dilated cardiomyopathy-like characteristics and

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Negative / Null Result ReportMedicine

Autoimmune pancreatitis and biliary intraepithelial neoplasia of the common bile duct: A case with diagnostically challenging but pathogenetically significant association

Haruo Ohtani, Hiroyasu Ishida, Yuka Ito et al. · 2011 · Pathology International

Autoimmune pancreatitis (AIP) (also called IgG4-related sclerosing pancreatitis (IgG4-SP)) and IgG4-related sclerosing cholangitis (IgG4-SC) are frequently associated with each other. It is generally believed that association of these…

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Negative / Null Result ReportOpen accessMedicine

Randomized, Double-Blind, Placebo-Controlled Phase III Study of Paclitaxel ± Napabucasin in Pretreated Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

Manish A. Shah, Kohei Shitara, Florian Lordick et al. · 2022 · Clinical Cancer Research

PURPOSE: To compare napabucasin (generator of reactive oxygen species) plus paclitaxel with paclitaxel only in patients with second-line advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. EXPERIMENTAL DESIGN: In the…

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Negative / Null Result ReportOpen accessMedicine

Orally active prostacyclin analogue beraprost sodium in patients with chronic kidney disease: a randomized, double-blind, placebo-controlled, phase II dose finding trial

Akio Kôyama, Toshiro Fujita, Fumitake Gejyo et al. · 2015 · BMC Nephrology

BACKGROUND: Evidence increasingly points to the importance of chronic hypoxia in the tubulointerstitium as a final common pathway to end-stage renal disease (ESRD). Beraprost sodium (BPS) is an orally active prostacyclin (PGI2) analogue demonstrating prevention of the progression of chronic kidney disease (CKD) in various animal models by maintaining renal blood flow and attenuating renal ischemic condition. METHODS: This multicenter, randomized, double-blind, placebo-controlled, phase II trial was designed to determine the recommended dose of the sustained-release form of BPS (TRK-100STP 120

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Failed Experiment ReportOpen accessMedicine

Epigenetic remodeling to improve the efficacy of immunotherapy in human glioblastoma: pre-clinical evidence for development of new immunotherapy approaches

Maria Fortunata Lofiego, Francesca Piazzini, Francesca Pia Caruso et al. · 2024 · Journal of Translational Medicine

BACKGROUND: Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor, that is refractory to standard treatment and to immunotherapy with immune-checkpoint inhibitors (ICI). Noteworthy, melanoma brain metastases (MM-BM), that share the same niche as GBM, frequently respond to current ICI therapies. Epigenetic modifications regulate GBM cellular proliferation, invasion, and prognosis and may negatively regulate the cross-talk between malignant cells and immune cells in the tumor milieu, likely contributing to limit the efficacy of ICI therapy of GBM. Thus, manipulating the tumor

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Negative / Null Result ReportOpen accessMedicine

Evaluation of the human adaptation of influenza A/H7N9 virus in PB2 protein using human and swine respiratory tract explant cultures

Louisa Chan, Christine T. H. Bui, Chris Ka Pun Mok et al. · 2016 · Scientific Reports

Novel avian H7N9 virus emerged in China in 2013 resulting in a case fatality rate of around 39% and continues to pose zoonotic and pandemic risk. Amino acid substitutions in PB2 protein were shown to influence the pathogenicity and transmissibility of H7N9 following experimental infection of ferrets and mice. In this study, we evaluated the role of amino acid substitution PB2-627K or compensatory changes at PB2-591K and PB2-701N, on the tropism and replication competence of H7N9 viruses for human and swine respiratory tracts using ex vivo organ explant cultures. Recombinant viruses of A/Shangh

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Negative / Null Result ReportOpen accessMedicine

ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels: a Mendelian randomization study

Dipender Gill, Marios Arvanitis, Paul Carter et al. · 2020 · Royal Society Open Science

Angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 have been implicated in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). The expression of ACE2 and TMPRSS2 in the lung epithelium might have implications for the risk of SARS-CoV-2 infection and severity of COVID-19. We use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to investigate whether these exposures affect lung ACE2 and TMPRSS2 gene expression and circ

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Negative / Null Result ReportOpen accessMedicine

Vitamin D3 and B12 supplementation in pregnancy

Bishwajit Bhowmik, Tasnima Siddiquee, Ibrahimu Mdala et al. · 2021 · Diabetes Research and Clinical Practice

AIM: To assess the efficacy of vitamin D3 or B12 supplementation during pregnancy. METHODS: Pregnant women at 6-14 weeks in the intervention arm received oral high dose intermittent vitamin D3 and/or low dose B12 supplementation if they…

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Negative / Null Result ReportOpen accessMedicine

Clinical Trial Risk in Non-Hodgkin’s Lymphoma: Endpoint and Target Selection

Jayson L. Parker, Zoe Yi Zhang, Rena Buckstein · 2011 · Journal of Pharmacy & Pharmaceutical Sciences

PURPOSE: To quantify the clinical trial risk of new drug development in Non-Hodgkin's lymphoma (NHL). Risk estimates for this disease have not been reported before. METHODS: We undertook a retrospective review of clinical trials in (NHL) in four subtypes to compare the success rate with the industry average. Our inclusion criteria required that a drug must initiate its phase I trial in one of the four NHL subtypes between 1998 and June 2008 in the US. In addition, clinical trials of new drug candidates that pertain to four subtypes of NHL were retrieved from clinicaltrial.gov. Drug candidates

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Failed Experiment ReportOpen accessMedicine

Geographic atrophy: pathophysiology and current therapeutic strategies

Kalpana Rajanala, Farokh Dotiwala, Arun K. Upadhyay · 2023 · Frontiers in Ophthalmology

Geographic atrophy (GA) is an advanced stage of age-related macular degeneration (AMD) that leads to gradual and permanent vision loss. GA is characterized by the loss of photoreceptor cells and retinal pigment epithelium (RPE), leading to distinct atrophic patches in the macula, which tends to increase with time. Patients with geographic atrophy often experience a gradual and painless loss of central vision, resulting in difficulty reading, recognizing faces, or performing activities that require detailed vision. The primary risk factor for the development of geographic atrophy is advanced ag

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Negative / Null Result ReportOpen accessMedicine

Final results of a phase II study of CHOEP plus lenalidomide as initial therapy for patients with stage II–IV peripheral T‐cell lymphoma

Robert Stuver, Steven M. Horwitz, Ranjana H. Advani et al. · 2023 · British Journal of Haematology

There remains no one standard induction for nodal-based peripheral T-cell lymphoma (PTCL). We conducted a phase II study of lenalidomide plus CHOEP as a novel induction strategy. Patients received CHOEP at standard doses in combination…

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Negative / Null Result ReportOpen accessMedicine

The Clinical Features of Children With Acute Fulminant Myocarditis and the Diagnostic and Follow-Up Value of Cardiovascular Magnetic Resonance

Jianli Lv, Bo Han, Cuiyan Wang et al. · 2019 · Frontiers in Pediatrics

Objective To investigate the clinical features and the diagnostic and follow-up value of acute fulminant myocarditis (AFM) in children. Methods 20 children diagnosed with AFM admitted to our department were reviewed, and the clinical manifestations; pathogenic examination results; myocardial injury biomarkers; and electrocardiography, echocardiogram and cardiovascular magnetic resonance (CMR) results were analyzed. Results The initial symptoms were abdominal pain, vomiting, fatigue, syncope, and convulsions. All children had significantly increased hs-cTnT and NT-pro BNP. In addition to nonspe

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Negative / Null Result ReportOpen accessMedicine

Clinical benefit of treatment with eribulin mesylate for metastatic triple‐negative breast cancer: Long‐term outcomes of patients treated in the US community oncology setting

Sarah S. Mougalian, Ronda Copher, Jonathan Kish et al. · 2018 · Cancer Medicine

INTRODUCTION: Real-world data are critical to demonstrate the consistency of evidence and external generalizability of randomized controlled trials (RCTs). This study examined characteristics and outcomes of metastatic triple-negative breast cancer (mTNBC) patients treated with eribulin mesylate at community oncology practices in the United States. METHODS: Physicians identified mTNBC patients initiating eribulin between 1 January 2011 and 1 January 2014 and abstracted data into an electronic case report form (eCRF). Eribulin treatment in the metastatic setting was categorized as early use (EU

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Negative / Null Result ReportOpen accessMedicine

Optimising the value of immunomodulatory drugs during induction and maintenance in transplant ineligible patients with newly diagnosed multiple myeloma: results from Myeloma XI, a multicentre, open‐label, randomised, Phase III trial

Graham Jackson, Charlotte Pawlyn, David A. Cairns et al. · 2020 · British Journal of Haematology

Second-generation immunomodulatory agents, such as lenalidomide, have a more favourable side-effect profile than the first-generation thalidomide, but their optimum combination and duration for patients with newly diagnosed transplant-ineligible myeloma (ND-TNE-MM) has not been defined. The most appropriate delivery and dosing regimens of these therapies for patients at advanced age and frailty status is also unclear. The Myeloma XI study compared cyclophosphamide, thalidomide and dexamethasone (CTDa) to cyclophosphamide, lenalidomide and dexamethasone (CRDa) as induction therapy, followed by

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Failed Experiment ReportOpen accessMedicine

New trials in resistant hypertension: mixed blessing stories

Carmine Zoccali, Francesca Mallamaci, Luca De Nicola et al. · 2023 · Clinical Kidney Journal

Resistant hypertension (RH) is linked to an increased risk of cardiovascular and renal complications. Treatment options include non-pharmacological interventions, such as lifestyle modifications, and the use of specific antihypertensive…

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Negative / Null Result ReportOpen accessMedicine

Design and baseline characteristics of the LANDMARK study

Etsuro Ogata, Masafumi Fukagawa, Hideki Hirakata et al. · 2016 · Clinical and Experimental Nephrology

BACKGROUND: Calcium (Ca)-based phosphate (P) binders, compared to non-Ca-based P binders, contribute to vascular calcification, which is associated with cardiovascular events. METHODS: The LANDMARK study is a multicenter, randomized, open-label, parallel comparative study of lanthanum carbonate (LC) and calcium carbonate (CC) in hemodialysis patients. Stable hemodialysis patients with intact parathyroid hormone ≤240 pg/mL meeting ≥1 of the following criteria (age >65 years, postmenopause, diabetes mellitus) were randomized into the LC and CC groups. LC group patients initially received LC 750

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Negative / Null Result ReportOpen accessMedicine

Uric acid as a predictor of endothelial dysfunction in patients with metabolic syndrome

Charanpreet Singh, Sanjay Jain, Veena Dhawan et al. · 2020 · Archives of Endocrinology and Metabolism

OBJECTIVE: We conducted a study to examine the association of endothelial dysfunction and oxidative stress with uric acid levels in patients of metabolic syndrome. METHODS: One hundred and two patients of Metabolic Syndrome (International Diabetes Federation definition) were included in the study. Anthropometric measurements, serum uric acid levels, fasting blood sugar levels and lipid levels, as well as malondialdehyde and reactive nitrogen intermediates were measured after an 8-hour fasting period. Flow mediated vasodilation (FMD) of the brachial artery was measured and endothelial dysfuncti

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Negative / Null Result ReportOpen accessMedicine

Blood Pressure Trajectories Prior to Death in Patients With Diabetes

Mary A.M. Rogers, Kathleen Ward, Tanya R. Gure et al. · 2011 · Diabetes Care

OBJECTIVE: The goals of this study were to examine trajectories of blood pressure (BP) in adults with diabetes and investigate the association of trajectory patterns with mortality. RESEARCH DESIGN AND METHODS: A nonconcurrent longitudinal…

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Negative / Null Result ReportOpen accessMedicine

Plasmodium falciparum gametocyte carriage in symptomatic patients shows significant association with genetically diverse infections, anaemia, and asexual stage density

Paul Sondo, Biébo Bihoun, Marc Christian Tahita et al. · 2021 · Malaria Journal

BACKGROUND: Multi-genotype malaria infections are frequent in endemic area, and people commonly harbour several genetically distinct Plasmodium falciparum variants. The influence of genetic multiplicity and whether some specific genetic variants are more or less likely to invest into gametocyte production is not clearly understood. This study explored host and parasite-related risk factors for gametocyte carriage, and the extent to which some specific P. falciparum genetic variants are associated with gametocyte carriage. METHODS: Gametocytes and asexual forms were detected by light microscopy

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Negative / Null Result ReportOpen accessMedicine

Hydroxychloroquine and short-course radiotherapy in elderly patients with newly diagnosed high-grade glioma: a randomized phase II trial

Lucy Brazil, Angela Swampillai, Ka Man Mak et al. · 2020 · Neuro-Oncology Advances

BACKGROUND: Effective treatment for patients at least 70 years with newly diagnosed glioblastoma remains challenging and alternatives to conventional cytotoxics are appealing. Autophagy inhibition has shown promising efficacy and safety in small studies of glioblastoma and other cancers. METHODS: We conducted a randomized phase II trial to compare radiotherapy with or without hydroxychloroquine (2:1 allocation). Patients aged at least 70 years with newly diagnosed high-grade glioma deemed suitable for short-course radiotherapy with an ECOG performance status of 0-1 were included. Radiotherapy

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Negative / Null Result ReportOpen accessMedicine

Current potential therapeutics of amyotrophic lateral sclerosis

Lijun Lu, Youqing Deng, Renshi Xu · 2024 · Frontiers in Neurology

Amyotrophic lateral sclerosis (ALS) is a debilitating motor neurological disorder for which there is still no cure. The disease seriously jeopardizes the health and lifespan of adult populations. The authors extensively retrieved the current literature about clinical and experimental ALS treatments. Based on them, this review primarily focused on summarizing the current potential clinical usage and trialing therapeutics of ALS. Currently, the clinical ALS treatments have focused primarily on relieving symptoms to improve the quality of life yet. There are a number of therapeutic approaches suc

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