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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

Sequential or Simultaneous Injection of Preformed Fibrils and AAV Overexpression of Alpha-Synuclein Are Equipotent in Producing Relevant Pathology and Behavioral Deficits

Matilde Negrini, Giuseppe Tomasello, Marcus Davidsson et al. · 2022 · Journal of Parkinson s Disease

BACKGROUND: Preclinical rodent models for Parkinson's disease (PD) based on viral human alpha-synuclein (h-αSyn) overexpression recapitulate some of the pathological hallmarks as it presents in humans, such as progressive cell loss and additional synucleinopathy in cortical and subcortical structures. Recent studies have combined viral vector-based overexpression of human wild-type αSyn with the sequential or simultaneous inoculation of preformed fibrils (PFFs) derived from human αSyn. OBJECTIVE: The goal of the study was to investigate whether sequential or combined delivery of the AAV vector

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Negative / Null Result ReportMedicine

Initiating acute dialysis at earlier Acute Kidney Injury Network stage in critically ill patients without traditional indications does not improve outcome: A prospective cohort study

Cynthia Ciwei Lim, Chieh Suai Tan, Manish Kaushik et al. · 2014 · Nephrology

AIM: Optimal timing for acute renal replacement therapy (ARRT) initiation in critically ill patients with acute kidney injury (AKI) is unclear. We aimed to evaluate outcomes in patients who initiated ARRT for traditional indications versus…

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Negative / Null Result ReportMedicine

The UK Experience of a Treatment Strategy for Pediatric Metastatic Medulloblastoma Comprising Intensive Induction Chemotherapy, Hyperfractionated Accelerated Radiotherapy and Response Directed High Dose Myeloablative Chemotherapy or Maintenance Chemothera

Sindu Vivekanandan, Richard Breene, Ramya Ramanujachar et al. · 2015 · Pediatric Blood & Cancer

BACKGROUND: Historically, the 5-year overall survival (OS) for metastatic medulloblastoma (MMB) was less than 40%. The strategy of post-operative induction chemotherapy (IC) followed by hyperfractionated accelerated radiotherapy (HART) and…

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Negative / Null Result ReportOpen accessMedicine

Targeting TREM-1 Signaling in the Presence of Antibiotics is Effective Against Streptococcal Toxic-Shock-Like Syndrome (STSLS) Caused by Streptococcus suis

Chao Yang, Jianqing Zhao, Lan Lin et al. · 2015 · Frontiers in Cellular and Infection Microbiology

Streptococcus suis (S.suis), a major swine pathogen, is also a severe threat to human health. Infection with highly virulent strains of S. suis can cause human Streptococcal toxic-shock-like syndrome (STSLS), which is associated with high serum pro-inflammatory cytokine levels and a high mortality rate. Our previous study indicated that highly virulent S. suis infection could activate the TREM-1 signaling pathway, which promotes host clearance of S. suis during early infection. However, it remained to be elicited whether TREM-1 signaling could be a target against STSLS in the presence of antib

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Negative / Null Result ReportOpen accessMedicine

Replicative Fitness Costs of Nonnucleoside Reverse Transcriptase Inhibitor Drug Resistance Mutations on HIV Subtype C

Kimberly L. Armstrong, Tun‐Hou Lee, Max Essex · 2011 · Antimicrobial Agents and Chemotherapy

Single-dose nevirapine (NVP) is quite effective in preventing transmission of the human immunodeficiency virus (HIV) from mother to child; however, many women develop resistance to NVP in this setting. Comparing outcomes of clinical studies reveals an increased amount of resistance in subtype C relative to that in other subtypes. This study investigates how nonnucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutations of subtype C affect replication capacity. The 103N, 106A, 106M, 181C, 188C, 188L, and 190A drug resistance mutations were placed in a reverse transcriptase (RT)

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Negative / Null Result ReportOpen accessMedicine

Adjuvant Therapeutic Modalities in Primary Small Cell Carcinoma of Esophagus Patients

Bingwen Zou, Tao Li, Qiang Zhou et al. · 2016 · Medicine

To evaluate the treatment pattern and survival of patients receiving radical resection for primary small cell carcinoma of the esophagus (PSCCE).This retrospective study included 150 patients who received radical resection of PSCCE. Data were retrieved from 4 centers in Western China. Thirty-nine of 150 patients received postoperative chemo-radiotherapy, 62 received postoperative chemotherapy, and 49 received radical resection only. The median radiation dosage was 50 Gy. The chemotherapeutic regimen was platinum-based and lasted for 2 to 6 cycles (median, 3).Median disease-free survival (mDFS)

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Negative / Null Result ReportOpen accessMedicine

Lenvatinib Plus Immune Checkpoint Inhibitors Improve Survival in Advanced Hepatocellular Carcinoma: A Retrospective Study

Xiaozhun Huang, Lin Xu, Teng Ma et al. · 2021 · Frontiers in Oncology

BACKGROUND: Nivolumab and pembrolizumab disrupt the programmed cell death-1 immune checkpoint and display promising efficacy and safety results in advanced hepatocellular carcinoma (HCC). However, the benefits remain limited. The preliminary results of lenvatinib (LEN) combined with immune checkpoint inhibitors (ICIs) reveal that the combinations were well-tolerated and encouraging. This study aimed to analyze the safety and efficacy of LEN plus ICIs in a real-world cohort of patients with advanced HCC. METHOD: Between June 4, 2017, and June 30, 2019, 16 patients received LEN plus nivolumab, a

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Negative / Null Result ReportOpen accessMedicine

Inhibition of Protein Kinase Cβ Does Not Improve Endothelial Function in Type 2 Diabetes

Joshua A. Beckman, Allison B. Goldfine, Alison Goldin et al. · 2010 · The Journal of Clinical Endocrinology & Metabolism

CONTEXT: Antagonism of protein kinase Cbeta (PKCbeta) restores endothelial function in experimental models of diabetes and prevents vascular dysfunction in response to hyperglycemia in healthy humans. OBJECTIVE: We tested the hypothesis…

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Negative / Null Result ReportOpen accessMedicine

Comparisons between Murine Polyomavirus and Simian Virus 40 Show Significant Differences in Small T Antigen Function

Shaida Andrabi, Justin H. Hwang, Jennifer Kean Choe et al. · 2011 · Journal of Virology

Although members of a virus family produce similar gene products, those products may have quite different functions. Simian virus 40 (SV40) large T antigen (LT), for example, targets p53 directly, but murine polyomavirus LT does not. SV40…

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Negative / Null Result ReportOpen accessMedicine

A Novel SARS-CoV-2 Viral Sequence Bioinformatic Pipeline Has Found Genetic Evidence That the Viral 3′ Untranslated Region (UTR) Is Evolving and Generating Increased Viral Diversity

Carlos Farkas, Andy Mella, Maxime Turgeon et al. · 2021 · Frontiers in Microbiology

An unprecedented amount of SARS-CoV-2 sequencing has been performed, however, novel bioinformatic tools to cope with and process these large datasets is needed. Here, we have devised a bioinformatic pipeline that inputs SARS-CoV-2 genome sequencing in FASTA/FASTQ format and outputs a single Variant Calling Format file that can be processed to obtain variant annotations and perform downstream population genetic testing. As proof of concept, we have analyzed over 229,000 SARS-CoV-2 viral sequences up until November 30, 2020. We have identified over 39,000 variants worldwide with increased polymo

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Negative / Null Result ReportOpen accessMedicine

Experimental infection of highly pathogenic avian influenza viruses, Clade 2.3.4.4 H5N6 and H5N8, in Mandarin ducks from South Korea

Kyung‐No Son, Yong-kwan Kim, Jae‐Ku Oem et al. · 2017 · Transboundary and Emerging Diseases

Outbreaks of highly pathogenic avian influenza (HPAI) have been reported worldwide. Wild waterfowl play a major role in the maintenance and transmission of HPAI. Highly pathogenic avian influenza subtype H5N6 and H5N8 viruses simultaneously emerged in South Korea. In this study, the comparative pathogenicity and infectivity of Clade 2.3.4.4 Group B H5N8 and Group C H5N6 viruses were evaluated in Mandarin duck (Aix galericulata). None of the ducks infected with H5N6 or H5N8 viruses showed clinical signs or mortality. Serological assays revealed that the HA antigenicity of H5N8 and H5N6 viruses

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Negative / Null Result ReportMedicine

Estimating the Additive Benefit of Surgical Excision to Stereotactic Radiosurgery in the Management of Metastatic Brain Disease

Matthew R. Quigley, Nicholas R. Bello, Diana H. Jho et al. · 2015 · Neurosurgery

BACKGROUND: There are limited data on the benefits of surgical tumor resection plus stereotactic radiosurgery (SRS) in comparison with SRS alone for patients with oligometastatic brain disease. OBJECTIVE: To determine the benefit of adding…

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Negative / Null Result ReportOpen accessMedicine

Natural killer cell functional genetics and donor-specific antibody-triggered microvascular inflammation

Matthias Diebold, Hannes Vietzen, Andreas Heinzel et al. · 2023 · American Journal of Transplantation

Antibody-mediated rejection (ABMR) is a leading cause of graft failure. Emerging evidence suggests a significant contribution of natural killer (NK) cells to microvascular inflammation (MVI). We investigated the influence of genetically determined NK cell functionality on ABMR development and activity. The study included 86 kidney transplant recipients subjected to systematic biopsies triggered by donor-specific antibody detection. We performed killer immunoglobulin-like receptor typing to predict missing self and genotyped polymorphisms determining NK cell functionality (FCGR3AV/F158 [rs39699

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Negative / Null Result ReportMedicine

Complete Atrioventricular Block does not Reduce Long-Term Mortality in Patients with Permanent Atrial Fibrillation Treated with Cardiac Resynchronization Therapy

José Marı́a Tolosana, Emilce Trucco, Malek Khatib et al. · 2013 · European Journal of Heart Failure

AIMS: A maximum percentage of ventricular pacing is mandatory to obtain a good response to CRT. Atrioventricular junction (AVJ) ablation has been recommended to attain this objective in patients with AF. THE AIMS OF OUR STUDY WERE: (i) to…

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Negative / Null Result ReportOpen accessMedicine

A validation study of the psychometric properties of the Groningen Reflection Ability Scale

Nina Bjerre Andersen, Lotte Dyhrberg O’Neill, Lise Kirstine Gormsen et al. · 2014 · BMC Medical Education

BACKGROUND: Reflection, the ability to examine critically one's own learning and functioning, is considered important for 'the good doctor'. The Groningen Reflection Ability Scale (GRAS) is an instrument measuring student reflection, which has not yet been validated beyond the original Dutch study. The aim of this study was to adapt GRAS for use in a Danish setting and to investigate the psychometric properties of GRAS-DK. METHODS: We performed a cross-cultural adaptation of GRAS from Dutch to Danish. Next, we collected primary data online, performed a retest, analysed data descriptively, esti

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Negative / Null Result ReportOpen accessMedicine

Mobile Money Use and Healthcare Utilization: Evidence from Rural Uganda

Hiroyuki Egami, Tomoya Matsumoto · 2020 · Sustainability

Lack of cash on hand is a significant obstacle in accessing healthcare services in developing countries. Many expectant mothers in the least developed countries do not receive sufficient care during pregnancy due to financial constraints. If such hurdles in accessing healthcare can be overcome, it will contribute to reduction in maternal and newborn mortality, which is a key target of Sustainable Development Goal 3. This study reports the first assessment of the impact of mobile money services on maternal care utilization. We hypothesize that mobile money adoption would motivate rural Ugandan

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Negative / Null Result ReportOpen accessMedicine

Cross-species transcriptome analysis for early detection and specific therapeutic targeting of human lupus nephritis

Eleni Frangou, Panagiotis Garantziotis, Maria Grigoriou et al. · 2022 · Annals of the Rheumatic Diseases

OBJECTIVES: Patients with lupus nephritis (LN) are in urgent need for early diagnosis and therapeutic interventions targeting aberrant molecular pathways enriched in affected kidneys. METHODS: We used mRNA-sequencing in effector (spleen) and target (kidneys, brain) tissues from lupus and control mice at sequential time points, and in the blood from 367 individuals (261 systemic lupus erythematosus (SLE) patients and 106 healthy individuals). Comparative cross-tissue and cross-species analyses were performed. The human dataset was split into training and validation sets and machine learning was

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Negative / Null Result ReportOpen accessMedicine

Progressive multiple sclerosis: Evaluating current therapies and exploring future treatment strategies

Marelisa Albelo-Martínez, Syed Rizvi · 2025 · Neurotherapeutics

Progressive forms of multiple sclerosis (MS) include primary progressive MS (PPMS) and secondary progressive MS (SPMS). Unlike relapsing-remitting MS (RRMS), progressive MS is recognized by relentless progression with accumulating disability, rare to no relapses nor new activity on MRIs. Clinically, neurologic worsening in MS can occur in the relapsing-remitting (RRMS) phase of disease due to incomplete recovery from neuroinflammatory relapses. However, a progressive disease course is the dominant factor related to accumulating disability. There is persistent central nervous system (CNS) compa

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Negative / Null Result ReportOpen accessMedicine

Six-Year Outcomes After Transcatheter vs Surgical Aortic Valve Replacement in Low-Risk Patients With Aortic Stenosis

John K. Forrest, Steven J. Yakubov, G. Michael Deeb et al. · 2026 · Journal of the American College of Cardiology

BACKGROUND: The Evolut Low Risk trial enrolled patients with severe aortic stenosis at low surgical risk. Annual follow-up is planned for 10 years, evaluating the composite of all-cause mortality or disabling stroke and key secondary…

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Negative / Null Result ReportOpen accessMedicine

Immunomodulatory Mechanisms of Chronic Wound Healing: Translational and Clinical Relevance

Mahrukh Riaz, Muhammad Zohaib Iqbal, Agnes S. Klar et al. · 2025 · MedComm

Chronic wounds-such as diabetic foot ulcers (DFUs), pressure ulcers (PUs), and venous leg ulcers (VLUs)-pose a serious clinical challenge due to their prolonged inflammatory phase and impaired healing. Increasing evidence reveals that dysregulated immune responses are central to the pathogenesis of chronic wounds. A complex interplay between innate and adaptive immune cells, including macrophages, neutrophils, and T cells, contributes to chronic inflammation, extracellular matrix (ECM) degradation, and tissue repair failure. While current treatments target symptoms, they often overlook the und

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Negative / Null Result ReportOpen accessMedicine

Collagenase-mediated extracellular matrix targeting for enhanced drug penetration and therapeutic efficacy in nanoscale delivery systems for cancer therapy

Pengyu Gong, Fei Wang, Yixin Hua et al. · 2025 · Journal of Nanobiotechnology

The highly fibrotic extracellular matrix (ECM) constitutes a major barrier that restricts the penetration and delivery efficiency of anticancer drugs, particularly in fibrotic tumors such as pancreatic cancer, in which cancer-associated…

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Negative / Null Result ReportOpen accessMedicine

EFFECT OF DIFFERENT BALANCE TRAINING PROGRAMS ON POSTURAL CONTROL IN CHRONIC ANKLE INSTABILITY: A RANDOMIZED CONTROLLED TRIAL

Noha Mahmoud Youssef, Azza Mohammed Abdelmohsen, Ahmed Atteya Ashour et al. · 2026 · PubMed

BACKGROUND: Chronic ankle instability (CAI) is a common sequence of ankle sprain. Conservative treatment of CAI is currently accepted as a primary mean of managing the condition and preventing of recurrence. OBJECTIVES: The purpose of the…

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Negative / Null Result ReportOpen accessMedicine

Acute minocycline administration reduces brain injury and improves long-term functional outcomes after delayed hypoxemia following traumatic brain injury

Marta Celorrio, Kirill Shumilov, Camryn Payne et al. · 2022 · Acta Neuropathologica Communications

Clinical trials of therapeutics for traumatic brain injury (TBI) demonstrating preclinical efficacy for TBI have failed to replicate these results in humans, in part due to the absence of clinically feasible therapeutic windows for administration. Minocycline, an inhibitor of microglial activation, has been shown to be neuroprotective when administered early after experimental TBI but detrimental when administered chronically to human TBI survivors. Rather than focusing on the rescue of primary injury with early administration of therapeutics which may not be clinically feasible, we hypothesiz

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Negative / Null Result ReportOpen accessMedicine

Diagnostic performance of plasma Aβ42/40 ratio, p‐tau181, GFAP, and NfL along the continuum of Alzheimer's disease and non‐AD dementias: An international multi‐center study

James D. Doecke, Giovanni Bellomo, Lisa Vermunt et al. · 2025 · Alzheimer s & Dementia

INTRODUCTION: Plasma phosphorylated tau (p-tau)181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and amyloid beta ratio (Aβ42/40) may have diagnostic and prognostic value in Alzheimer's disease (AD). Here we assess which markers can best identify AD from controls and other non-AD dementias in a large international multi-center study. METHODS: Plasma samples (n = 1298) were collected from six international centers. Aβ40, Aβ42, GFAP, NfL, and p-tau181 were measured using single molecule array. In each group, AD diagnosis/co-pathology was defined according to cerebrosp

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Negative / Null Result ReportOpen accessMedicine

Type 2 Diabetes and the Multifaceted Gut-X Axes

Hezixian Guo, L.-T. Pan, Qiuyi Wu et al. · 2025 · Nutrients

Type 2 diabetes (T2D) is a complex metabolic disease characterized by chronic hyperglycemia due to insulin resistance and inadequate insulin secretion. Beyond the classically implicated organs, emerging evidence highlights the gut as a central player in T2D pathophysiology through its interactions with metabolic organs. The gut hosts trillions of microbes and enteroendocrine cells that influence inflammation, energy homeostasis, and hormone regulation. Disruptions in gut homeostasis (dysbiosis and increased permeability) have been linked to obesity, insulin resistance, and β-cell dysfunction,

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