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Browse the failure-mode index

12,368 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

Immunization with a Trypanosoma cruzi cyclophilin-19 deletion mutant protects against acute Chagas disease in mice

Bijay Kumar Jha, Sanjay Varikuti, Chaitenya Verma et al. · 2023 · npj Vaccines

Human infection with the protozoan parasite Trypanosoma cruzi causes Chagas disease for which there are no prophylactic vaccines. Cyclophilin 19 is a secreted cis-trans peptidyl isomerase expressed in all life stages of Trypanosoma cruzi. This protein in the insect stage leads to the inactivation of insect anti-parasitic peptides and parasite transformation whereas in the intracellular amastigotes it participates in generating ROS promoting the growth of parasites. We have generated a parasite mutant with depleted expression of Cyp19 by removal of 2 of 3 genes encoding this protein using doubl

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Negative / Null Result ReportOpen accessMedicine

A Significant Effect of Pemafibrate on Hepatic Steatosis and Fibrosis Indexes in Patients With Hypertriglyceridemia

Hisayuki Katsuyama, Hidekatsu Yanai, Hiroki Adachi et al. · 2023 · Gastroenterology Research

Background: We previously reported that the selective peroxisome proliferator-activated receptor alpha modulator, pemafibrate, significantly reduced serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and…

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Negative / Null Result ReportOpen accessMedicine

Systemic Therapies for HER2-Positive Advanced Breast Cancer

Vasileios Angelis, Alicia Okines · 2023 · Cancers

Despite recent advances, HER2-positive advanced breast cancer (ABC) remains a largely incurable disease, with resistance to conventional anti-HER2 drugs ultimately unavoidable for all but a small minority of patients who achieve an enduring remission and possibly cure. Over the past two decades, significant advances in our understanding of the underlying molecular mechanisms of HER2-driven oncogenesis have translated into pharmaceutical advances, with the developing of increasingly sophisticated therapies directed against HER2. These include novel, more potent selective HER2 tyrosine kinase in

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Negative / Null Result ReportOpen accessMedicine

Antineoplastic Drug Synergy of Artesunate with Navitoclax in Models of High-Grade Serous Ovarian Cancer

J. Robert McCorkle, Rebecca Ahn, Connie D. Cao et al. · 2024 · Cancers

) known as artemisinins. Artesunate has traditionally been used as a frontline treatment for severe malaria but has also demonstrated antineoplastic activity against various malignancies, including ovarian cancer. Data suggest that artesunate exacerbates cellular oxidative stress, triggering apoptosis. In the current study, we investigated the ability of navitoclax, an inhibitor of the antiapoptotic Bcl-2 protein family, to enhance artesunate efficacy in ovarian cancer cells. Artesunate and navitoclax both demonstrated antiproliferative effects on 2D and 3D ovarian cancer cell models as single

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Negative / Null Result ReportOpen accessMedicine

Hepatic artery infusion of FOLFOX chemotherapy plus camrelizumab combined with sorafenib for advanced hepatocellular carcinoma in Barcelona Clinic Liver Cancer stage C (Double-IA-001): a phase II trial

Lujun Shen, Fei Cao, Ying Liu et al. · 2025 · BMC Medicine

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) with a combination of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown excellent local control for patients with Barcelona Clinic Liver Cancer (BCLC) stage C…

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Negative / Null Result ReportOpen accessMedicine

Replication of SARS-CoV-2 in cell lines used in public health surveillance programmes with special emphasis on biosafety

Shailesh D. Pawar, Sadhana S. Kode, Sachin S. Keng et al. · 2022 · The Indian Journal of Medical Research

Background & objectives Polio, measles, rubella, influenza and rotavirus surveillance programmes are of great public health importance globally. Virus isolation using cell culture is an integral part of such programmes. Possibility of…

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Negative / Null Result ReportOpen accessMedicine

Vaccines targeting the primary amino acid sequence and conformational epitope of amyloid‐β had distinct effects on neuropathology and cognitive deficits in EAE/AD mice

Xiaolin Yu, Jie Zhu, Xiang‐meng Liu et al. · 2020 · British Journal of Pharmacology

BACKGROUND AND PURPOSE: Immunotherapeutic intervention is one of the most promising strategies for the prevention and treatment of Alzheimer's disease (AD). Although they showed great success in AD mouse models, the clinical trials of many…

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Negative / Null Result ReportOpen accessMedicine

Feasibility study of mobile phone photography as a possible outcome measure of systemic sclerosis-related digital lesions

Adrian K. Davison, Graham Dinsdale, Paul New et al. · 2022 · Rheumatology Advances in Practice

Objective: Clinical trials assessing systemic sclerosis (SSc)-related digital ulcers have been hampered by a lack of reliable outcome measures of healing. Our objective was to assess the feasibility of patients collecting high-quality mobile phone images of their digital lesions as a first step in developing a smartphone-based outcome measure. Methods: Patients with SSc-related digital (finger) lesions photographed one or more lesions each day for 30 days using their smartphone and uploaded the images to a secure Dropbox folder. Image quality was assessed using six criteria: blurriness, shadow

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Negative / Null Result ReportOpen accessMedicine

Milademetan in Advanced Solid Tumors with MDM2 Amplification and Wild-type TP53: Preclinical and Phase II Clinical Trial Results

Ecaterina E. Dumbrava, Thomas E. Stinchcombe, Mrinal M. Gounder et al. · 2025 · Clinical Cancer Research

PURPOSE: Mouse double minute 2 (MDM2) is an E3 ubiquitin ligase that degrades the tumor suppressor p53. In cancers, MDM2 amplification (MDM2amp) leads to overexpression of MDM2, inducing p53 degradation and a p53-null phenotype even in the…

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Negative / Null Result ReportOpen accessMedicine

Replication of genetic associations of chemotherapy-related cardiotoxicity in the adjuvant NSABP B-31 clinical trial

Pooja Advani, Kathryn J. Ruddy, Joerg Herrmann et al. · 2023 · Frontiers in Oncology

Background The cardiotoxic effects of doxorubicin, trastuzumab, and other anticancer agents are well known, but molecular genetic testing is lacking for the early identification of patients at risk for therapy-related cardiac toxicity. Methods Using the Agena Bioscience MassARRAY system, we genotyped TRPC6 rs77679196, BRINP1 rs62568637, LDB2 rs55756123, RAB22A rs707557, intergenic rs4305714, LINC01060 rs7698718, and CBR3 rs1056892 (V244M) (previously associated with either doxorubicin or trastuzumab-related cardiotoxicity in the NCCTG N9831 trial of anthracycline-based chemotherapy ± trastuzum

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Negative / Null Result ReportOpen accessMedicine

In vivo serotonin 1A receptor hippocampal binding potential in depression and reported childhood adversity

Elizabeth Bartlett, Ashley Yttredahl, Maura Boldrini et al. · 2023 · European Psychiatry

Abstract Background Reported childhood adversity (CA) is associated with development of depression in adulthood and predicts a more severe course of illness. Although elevated serotonin 1A receptor (5-HT 1A R) binding potential, especially…

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Negative / Null Result ReportOpen accessMedicine

Lack of benefit from hospitalization in patients with syncope: A propensity analysis

Padma Kaul, Dat T. Tran, Roopinder K. Sandhu et al. · 2020 · Journal of the American College of Emergency Physicians Open

STUDY OBJECTIVE: Patients with syncope are frequently admitted to the hospital, but whether this improves outcome is unknown. We tested whether hospitalization reduced mortality in patients who presented to emergency departments (EDs) with…

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Negative / Null Result ReportOpen accessMedicine

Prediction of Radiation-Induced Hypothyroidism Using Radiomic Data Analysis Does Not Show Superiority over Standard Normal Tissue Complication Models

Urszula Smyczyńska, Szymon Grabia, Zuzanna Nowicka et al. · 2021 · Cancers

State-of-art normal tissue complication probability (NTCP) models do not take into account more complex individual anatomical variations, which can be objectively quantitated and compared in radiomic analysis. The goal of this project was development of radiomic NTCP model for radiation-induced hypothyroidism (RIHT) using imaging biomarkers (radiomics). We gathered CT images and clinical data from 98 patients, who underwent intensity-modulated radiation therapy (IMRT) for head and neck cancers with a planned total dose of 70.0 Gy (33–35 fractions). During the 28-month (median) follow-up 27 pat

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Negative / Null Result ReportOpen accessMedicine

The Binary Model of Chronic Diseases Applied to COVID-19

Zeev Elkoshi · 2021 · Frontiers in Immunology

A binary model for the classification of chronic diseases has formerly been proposed. The model classifies chronic diseases as “high Treg” or “low Treg” diseases according to the extent of regulatory T cells (Treg) activity (frequency or function) observed. The present paper applies this model to severe acute respiratory syndrome coronavirus 2 (SARS - CoV - 2) infection. The model correctly predicts the efficacy or inefficacy of several immune-modulating drugs in the treatment of severe coronavirus disease 2019 (COVID-19) disease. It also correctly predicts the class of pathogens mostly associ

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Negative / Null Result ReportOpen accessMedicine

Effect of the index of cardiac electrophysiological balance on major adverse cardiovascular events in patients with diabetes complicated with coronary heart disease

Yuan Lin, Fang Zhou, Xihui Wang et al. · 2023 · PeerJ

Purpose: To investigate the prognostic value of the index of cardio-electrophysiological balance (ICEB) and its association with major adverse cardiac events (MACE) and cardiovascular death in diabetic patients complicated with coronary heart disease. Methods: A total of 920 diabetic patients were enrolled in this longitudinal study. Participants were categorized into three groups based on their ICEB levels: normal ICEB, low ICEB, and high ICEB. The primary outcome was the occurrence of MACE, and secondary outcomes included cardiovascular death, coronary heart disease (CHD), heart failure (HF)

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Negative / Null Result ReportOpen accessMedicine

Emergent immunotherapy approaches for brain metastases

Jianbo Wang, Hussein A. Tawbi · 2021 · Neuro-Oncology Advances

Brain metastases from solid tumors are increasing in incidence, especially as outcomes of systemic therapies continue to extend patients' overall survival. The long-held notion that the brain is an immune sanctuary has now been largely…

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Negative / Null Result ReportOpen accessMedicine

On the Rapid Calculation of Binding Affinities for Antigen and Antibody Design and Affinity Maturation Simulations

Simone Conti, Edmond Y. Lau, Victor Ovchinnikov · 2022 · Antibodies

The accurate and efficient calculation of protein-protein binding affinities is an essential component in antibody and antigen design and optimization, and in computer modeling of antibody affinity maturation. Such calculations remain challenging despite advances in computer hardware and algorithms, primarily because proteins are flexible molecules, and thus, require explicit or implicit incorporation of multiple conformational states into the computational procedure. The astronomical size of the amino acid sequence space further compounds the challenge by requiring predictions to be computed

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Negative / Null Result ReportOpen accessMedicine

Erythrocytosis incidence and thromboembolic risk in heart failure with reduced ejection fraction treated with SGLT2 inhibitors: a nationwide register-based cohort study

Abdullahi Ahmed Mohamed, Camilla Fuchs Andersen, Daniel Mølager Christensen et al. · 2025 · Cardiovascular Diabetology

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) increase haemoglobin and haematocrit levels, potentially causing secondary erythrocytosis-defined as a haemoglobin level above 16.5 g/dL in men and 16.0 g/dL in women-which is…

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Negative / Null Result ReportOpen accessMedicine

The Price of Explainability in Machine Learning Models for 100-Day Readmission Prediction in Heart Failure: Retrospective, Comparative, Machine Learning Study

Amira Soliman, Björn Agvall, Kobra Etminani et al. · 2023 · Journal of Medical Internet Research

BACKGROUND: Sensitive and interpretable machine learning (ML) models can provide valuable assistance to clinicians in managing patients with heart failure (HF) at discharge by identifying individual factors associated with a high risk of readmission. In this cohort study, we delve into the factors driving the potential utility of classification models as decision support tools for predicting readmissions in patients with HF. OBJECTIVE: The primary objective of this study is to assess the trade-off between using deep learning (DL) and traditional ML models to identify the risk of 100-day readmi

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Negative / Null Result ReportOpen accessMedicine

An exploratory study to evaluate visual function endpoints in non-advanced age-related macular degeneration

Divya Narayanan, John David Rodriguez, Garrick Wallstrom et al. · 2020 · BMC Ophthalmology

BACKGROUND: To prevent irreversible vision loss in age-related macular degeneration (AMD), it is critical to detect retinal dysfunction before permanent structural loss occurs. In the current study we evaluated a series of visual function tests to identify potential endpoints to detect visual dysfunction in non-advanced AMD. METHODS: A series of visual function tests were performed on 23 non-advanced AMD subjects (AREDS grade 1-4 on simplified scale) and 34 age-matched normals (AREDS grade 0). Tests included some commonly used endpoints such as ETDRS visual acuity (VA), low luminance (LL) 2.0N

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Negative / Null Result ReportMedicine

Ganciclovir Therapy for CMV Viremia in a Patient on VV ECMO With COVID-19 After Treatment With Tocilizumab

Leah Amundson, Brandon Boelts, Vivek Kataria et al. · 2021 · Infectious Diseases in Clinical Practice

To the Editor: Coronavirus disease 2019 (COVID-19) has resulted in a widespread pandemic in which various therapeutics have been studied. Targeted therapies focus on either the viral or the inflammatory phase to ultimately reduce disease…

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Negative / Null Result ReportOpen accessMedicine

Epidemiology of childhood acute kidney injury in England using e-alerts

Lucy Plumb, Anna Casula, Manish D. Sinha et al. · 2023 · Clinical Kidney Journal

ABSTRACT Background Few studies describe the epidemiology of childhood acute kidney injury (AKI) nationally. Laboratories in England are required to issue electronic (e-)alerts for AKI based on serum creatinine changes. This study…

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Negative / Null Result ReportOpen accessMedicine

Ratcheting down the virulence of SARS‐CoV‐2 in the COVID‐19 pandemic

Adam Brufsky, Michael T. Lotze · 2020 · Journal of Medical Virology

Muller's ratchet1 predicts that when mutation rates are high and a significant proportion of mutations are deleterious, a kind of irreversible ratchet mechanism will gradually decrease the mean fitness of small populations of asexual organisms.2 In cell culture, serial passage of genetically bottlenecked vesicular stomatitis virus, which grew quite rapidly on HeLa cells, severely reduced in fitness and virulence within 20 passages in a novel BHK host cell.2 Genetic bottlenecks are likely important in intraspecies viral transmission.3 RNA-based viruses are particularly prone to repeated bottlen

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Negative / Null Result ReportOpen accessMedicine

A genome‐wide association study of obstructive heart defects among participants in the National Birth Defects Prevention Study

Sara R. Rashkin, Mario A. Cleves, Gary M. Shaw et al. · 2022 · American Journal of Medical Genetics Part A

Abstract Obstructive heart defects (OHDs) share common structural lesions in arteries and cardiac valves, accounting for ~25% of all congenital heart defects. OHDs are highly heritable, resulting from interplay among maternal exposures,…

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