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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

Evaluating the Safety of Maribavir for the Treatment of Cytomegalovirus

Ronak G Gandhi, Camille N Kotton · 2022 · Therapeutics and Clinical Risk Management

Purpose of Review: Cytomegalovirus (CMV) infections are a common complication in solid organ (SOT) and hematopoietic stem cell transplant (HSCT) recipients, leading to increased morbidity and mortality. Currently available treatment…

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Negative / Null Result ReportOpen accessMedicine

Genetic susceptibility loci of idiopathic interstitial pneumonia do not represent risk for systemic sclerosis: a case control study in Caucasian patients

Minghua Wu, Shervin Assassi, Gloria A. Salazar et al. · 2016 · Arthritis Research & Therapy

BACKGROUND: Systemic sclerosis (SSc)-related interstitial lung disease (ILD) has phenotypic similarities to lung involvement in idiopathic interstitial pneumonia (IIP). We aimed to assess whether genetic susceptibility loci recently identified in the large IIP genome-wide association studies (GWASs) were also risk loci for SSc overall or severity of ILD in SSc. METHODS: A total of 2571 SSc patients and 4500 healthy controls were investigated from the US discovery GWAS and additional US replication cohorts. Thirteen IIP-related selected single nucleotide polymorphisms (SNPs) were genotyped and

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Negative / Null Result ReportOpen accessMedicine

Novel Protease Inhibitors (PIs) Containing Macrocyclic Components and 3( R ),3a( S ),6a( R )- bis -Tetrahydrofuranylurethane That Are Potent against Multi-PI-Resistant HIV-1 Variants In Vitro

Yasushi Tojo, Yasuhiro Koh, Masayuki Amano et al. · 2010 · Antimicrobial Agents and Chemotherapy

Natural products with macrocyclic structural features often display intriguing biological properties. Molecular design incorporating macrocycles may lead to molecules with unique protein-ligand interactions. We generated novel human…

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Negative / Null Result ReportOpen accessMedicine

Predictors for Survival in an International Cohort of Patients Undergoing Distal Pancreatectomy for Pancreatic Ductal Adenocarcinoma

Maarten Korrel, Sanne Lof, Jony van Hilst et al. · 2020 · Annals of Surgical Oncology

BACKGROUND: Surgical factors, including resection of Gerota's fascia, R0-resection, and lymph node yield, may be associated with survival after distal pancreatectomy (DP) for pancreatic ductal adenocarcinoma (PDAC), but evidence from large multicenter studies is lacking. This study aimed to identify predictors for overall survival after DP for PDAC, especially those related to surgical technique. PATIENTS AND METHODS: Data from an international retrospective cohort including patients from 11 European countries and the USA who underwent DP for PDAC (2007-2015) were analyzed. Cox proportional ha

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Negative / Null Result ReportOpen accessMedicine

Interferon-based agents for current and future viral respiratory infections: A scoping literature review of human studies

Aldina Mešić, Emahlea Jackson, Mathias Lalika et al. · 2022 · PLOS Global Public Health

The interferon (IFN) system is a potent line of defense against viral infections. IFN-based agents already tested may be of use in COVID-19 or future viral respiratory outbreaks. Here we review the comparative efficacy, safety/tolerability, and future potential of IFN-based therapeutics. We reviewed human studies in which IFN or IFN pathway-interacting agents were used for viral respiratory infections. We identified 977 articles, of which 194 were included for full-text review. Of these, we deemed 35 articles to be relevant. The use of IFN-based agents for pre-exposure prophylaxis (n = 19) and

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Negative / Null Result ReportOpen accessMedicine

Genetic Association Analysis in a Clinically and Histologically Confirmed Otosclerosis Population Confirms Association With the TGFB1 Gene but Suggests an Association of the RELN Gene With a Clinically Indistinguishable Otosclerosis-Like Phenotype

Manou Sommen, Guy Van Camp, Balázs Liktor et al. · 2014 · Otology & Neurotology

BACKGROUND/HYPOTHESIS: Otosclerosis is a frequent cause of hearing impairment characterized by abnormal resorption and deposition of bone in the human otic capsule. It is a disease of complex etiopathogenesis that is caused by both…

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Negative / Null Result ReportOpen accessMedicine

Novel Treatment Strategies for Hormone Receptor (HR)-Positive, HER2-Negative Metastatic Breast Cancer

Antonella Ferro, Michela Campora, A. Caldara et al. · 2024 · Journal of Clinical Medicine

Estrogen receptor (ER)-positive breast cancer (BC) is the most common BC subtype. Endocrine therapy (ET) targeting ER signaling still remains the mainstay treatment option for hormone receptor (HR)-positive BC either in the early or in advanced setting, including different strategies, such as the suppression of estrogen production or directly blocking the ER pathway through SERMs—selective estrogen receptor modulators—or SERDs—selective estrogen receptor degraders. Nevertheless, the development of de novo or acquired endocrine resistance still remains challenging for oncologists. The use of no

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Negative / Null Result ReportMedicine

Genetic basis of polycystic ovary syndrome

TM Barber, Stephen Franks · 2010 · Expert Review of Endocrinology & Metabolism

Polycystic ovary syndrome (PCOS) is associated with obesity and manifests with reproductive, hyperandrogenic and metabolic features. Although the etiology of PCOS is complex and incompletely understood, genetics plays an important role…

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Negative / Null Result ReportOpen accessMedicine

Overlooked Candida glabrata petites are echinocandin tolerant, induce host inflammatory responses, and display poor in vivo fitness

Amir Arastehfar, Farnaz Daneshnia, Hrant Hovhannisyan et al. · 2023 · mBio

ABSTRACT Small colony variants are relatively common among some bacterial species and are associated with poor prognosis and recalcitrant infections. Similarly, Candida glabrata— a major intracellular fungal pathogen—produces small and slow-growing respiratory-deficient colonies, termed “petite.” Despite reports of clinical petite C. glabrata strains, our understanding of petite behavior in the host remains obscure. Moreover, controversies exist regarding in-host petite fitness and its clinical relevance. Herein, we employed whole-genome sequencing (WGS), dual-RNAseq, and extensive ex vivo and

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Negative / Null Result ReportOpen accessMedicine

Patterns of failure after multimodal treatments for high-grade glioma: effectiveness of MIB-1 labeling index

Kazuyuki Uehara, Takashi Sasayama, Daisuke Miyawaki et al. · 2012 · Radiation Oncology

BACKGROUND: The purpose of the present study was to analyze the recurrence pattern of high-grade glioma treated with a multimodal treatment approach and to evaluate whether the MIB-1 labeling index (LI) could be a useful marker for predicting the pattern of failure in glioblastoma (GB). METHODS AND MATERIALS: We evaluated histologically confirmed 131 patients with either anaplastic astrocytoma (AA) or GB. A median dose was 60 Gy. Concomitant and adjuvant chemotherapy were administered to 111 patients. MIB-1 LI was assessed by immunohistochemistry. Recurrence patterns were categorized according

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Negative / Null Result ReportOpen accessMedicine

The reliability characteristics of the REFLECT rubric for assessing reflective capacity through expressive writing assignments: A replication study

Lawrence Grierson, Samantha Winemaker, Alan Taniguchi et al. · 2020 · Perspectives on Medical Education

INTRODUCTION: The medical education community has implemented writing exercises that foster critical analysis and nurture reflective capacity. The REFLECT rubric (Wald et al. 2012) was developed to address the challenge of assessing these written reflections. The objective of this replication work is to explore the reproducibility of the reliability characteristics presented by the REFLECT developers. METHODS: Five raters evaluated narratives written by medical students and experienced clinicians using the REFLECT rubric. Reliability across rubric domains was determined via intraclass correlat

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Negative / Null Result ReportOpen accessMedicine

The V Protein of Canine Distemper Virus Is Required for Virus Replication in Human Epithelial Cells

Noriyuki Otsuki, Yuichiro Nakatsu, Toru Kubota et al. · 2013 · PLoS ONE

Canine distemper virus (CDV) becomes able to use human receptors through a single amino acid substitution in the H protein. In addition, CDV strains possessing an intact C protein replicate well in human epithelial H358 cells. The present study showed that CDV strain 007Lm, which was isolated from lymph node tissue of a dog with distemper, failed to replicate in H358 cells, although it possessed an intact C protein. Sequence analyses suggested that a cysteine-to-tyrosine substitution at position 267 of the V protein caused this growth defect. Analyses using H358 cells constitutively expressing

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Negative / Null Result ReportOpen accessMedicine

Treatment of chronic leg ulcers with a hydrocolloid dressing

P. Gamborg Nielsen, S Madsen, L. Strömberg · 2026 · Acta Dermato Venereologica

The effects of a hydrocolloid dressing (Comfeel Ulcus) on the physical environment of chronic leg ulcers in 58 consecutive out-patients were investigated. Patients were subdivided into two groups of which Group 1 included 31 (53.4%) and…

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Negative / Null Result ReportOpen accessMedicine

Effect of Lactobacillus plantarum supplementation on trimethylamine-N-oxide levels in 30 patients with atherosclerotic cardiovascular disease: A double-blind randomized controlled trial

Natalia Spasova, Desislava Somleva, Bozhidar Krastev et al. · 2024 · Folia Medica

Introduction : Trimethylamine-N-oxide (TMAO) is a metabolite produced by intestinal microbiota. It is well recognized as an independent risk marker for cardiovascular and renal diseases and mortality. Aim : The aim of the present study was…

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Replication FailureOpen accessMedicine

The Effect of Genetic Variation on the Placental Transcriptome in Humans

Triin Kikas, Kristiina Rull, Robin N. Beaumont et al. · 2019 · Frontiers in Genetics

= 6830) did not replicate these findings. In summary, the study emphasizes the role of genetic variation in driving the transcriptome profile of the human placenta and the importance to explore further its functional implications.

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Negative / Null Result ReportOpen accessMedicine

GLP-1 and the Degenerating Brain: Exploring Mechanistic Insights and Therapeutic Potential

Osama Sobhi Moaket, Sarah Eyad Obaid, Fawaz Eyad Obaid et al. · 2025 · International Journal of Molecular Sciences

Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), stroke, and depression, are marked by progressive neuronal dysfunction and loss, yet current treatments remain largely symptomatic with limited disease-modifying efficacy. Glucagon-like peptide-1 (GLP-1), an incretin hormone traditionally associated with metabolic regulation, has emerged as a promising neuroprotective agent. Its receptor, GLP-1R, is expressed in key brain regions implicated in cognition, emotion, and motor control, including the hippocampus, frontal cortex, and substantia nigra. GLP-1R a

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Negative / Null Result ReportOpen accessMedicine

Overcoming resistance to PD-1 and CTLA-4 blockade mechanisms and therapeutic strategies

Xiaodong Wang, Jing He, Gouping Ding et al. · 2025 · Frontiers in Immunology

Immune checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4 have achieved groundbreaking clinical success in multiple cancers; however, a large proportion of patients experience primary or acquired resistance. This review synthesizes the complex mechanisms underlying resistance to PD-1/CTLA-4 blockade and surveys emerging strategies to overcome them. Resistance arises from multifaceted interactions among tumor-intrinsic alterations (e.g., epigenetic silencing of antigen presentation machinery via EZH2/PRC2, oncogenic pathway-driven upregulation of PD-L1, genetic loss of IFNγ pathway componen

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Failed Experiment ReportOpen accessMedicine

Bone Health Outcomes from the International, Multicenter, Randomized, Phase 3, Placebo-Controlled D-CARE Study Assessing Adjuvant Denosumab in Early Breast Cancer

Robert E. Coleman, Ying Zhou, Danielle Jandial et al. · 2021 · Advances in Therapy

INTRODUCTION: D-CARE, an international, phase 3, randomized, double-blind, placebo-controlled study in women with early-stage breast cancer at high risk of disease recurrence, failed to meet its primary endpoint-improvement in bone…

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Negative / Null Result ReportOpen accessMedicine

Estimated GFR and Mortality in Older Men: Are All eGFR Formulae Equal?

Muna Canales, Terri Blackwell, Areef Ishani et al. · 2016 · American Journal of Nephrology

<b><i>Background:</i></b> Recently, the first estimated glomerular filtration rate (eGFR) formula specifically developed for community-dwelling older adults, the Berlin Initiative Study Equation 2 (BIS2), was…

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Negative / Null Result ReportOpen accessMedicine

Association of maternal pre-pregnancy BMI and breastfeeding with NAFLD in young adults: a parental negative control study

Kushala Abeysekera, James Orr, Paul Madley‐Dowd et al. · 2021 · The Lancet Regional Health - Europe

BACKGROUND: The importance of the maternal-infant dyad in the genesis of nonalcoholic fatty liver disease (NAFLD) is of increasing interest. The Avon Longitudinal Study of Parents and Children (ALSPAC) showed that at age 24, 1 in 5 had…

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Negative / Null Result ReportOpen accessMedicine

Treatment of 4T1 Metastatic Breast Cancer with Combined Hypofractionated Irradiation and Autologous T-Cell Infusion

Alexander Filatenkov, Jeanette Baker, Antonia Müller et al. · 2014 · Radiation Research

The goal of this study was to determine whether a combination of local tumor irradiation and autologous T-cell transplantation can effectively treat metastatic 4T1 breast cancer in mice. BALB/c mice were injected subcutaneously with…

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Replication FailureMedicine

A multicenter randomized controlled trial (RCT) of adjuvant chemotherapy (CT) in nasopharyngeal carcinoma (NPC) with residual plasma EBV DNA (EBV DNA) following primary radiotherapy (RT) or chemoradiation (CRT).

Anthony T.�C. Chan, Edwin P. Hui, Roger K.C. Ngan et al. · 2017 · Journal of Clinical Oncology

6002 Background: The benefit of adjuvant CT in NPC is unclear. Post-RT EBV DNA predicts poor survival and may be a biomarker of subclinical residual disease. We conducted a biomarker driven RCT using post-RT EBV DNA to select high risk NPC…

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Negative / Null Result ReportMedicine

Clinically Significant Differences in Ki-67 Proliferation Index Between Primary and Metastases in Resected Pancreatic Neuroendocrine Tumors

Sebastian Richards-Taylor, Charles Tilley, Eleanor Jaynes et al. · 2017 · Pancreas

OBJECTIVE: Pancreatic neuroendocrine tumors (NETs) (pNETs) have a varied prognosis according to their grade. The European Neuroendocrine Tumor Society grading system uses assessment of the proliferation index via Ki-67 immunohistochemistry…

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Negative / Null Result ReportOpen accessMedicine

DOES HIPEC IMPROVE OUTCOMES IN GASTRIC CANCER PATIENTS TREATED WITH PERIOPERATIVE CHEMOTHERAPY AND RADICAL SURGERY? A PROPENSITY-SCORE MATCHED ANALYSIS

Thiago Pereira Diniz, Wilson Luiz da Costa, Victor Hugo Fonseca de Jesus et al. · 2019 · Journal of Surgical Oncology

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) has been associated with improved survival when compared with surgery alone for non-metastatic gastric cancer patients in randomized trials and meta-analyses. However, little evidence is available regarding the use of HIPEC in nonmetastatic patients who are treated with perioperative chemotherapy and radical surgery. The aim of this study was to investigate the putative survival benefit of HIPEC in the subgroup of gastric cancer patients treated with perioperative chemotherapy and surgery. PATIENTS AND METHODS: This was a retrospect

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