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Browse the failure-mode index

12,222 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

Differential Associations of UPPS-P Impulsivity Traits With Alcohol Problems

Kayleigh N. McCarty, David H. Morris, Laura E. Hatz et al. · 2017 · Journal of Studies on Alcohol and Drugs

OBJECTIVE: The UPPS-P model posits that impulsivity comprises five factors: positive urgency, negative urgency, lack of planning, lack of perseverance, and sensation seeking. Negative and positive urgency are the traits most consistently…

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Failed Experiment ReportOpen accessMedicine

Neoadjuvant chemotherapy and Avelumab in early stage resectable nonsmall cell lung cancer

Arafat Tfayli, Majd Al Assaad, Ghina Fakhri et al. · 2020 · Cancer Medicine

Multiple randomized studies have shown that combination of chemotherapy and immune checkpoint inhibitors (ICIs) leads to better response rates and survival as compared to chemotherapy alone in the advanced stage of NSCLC. Data suggesting a benefit to using ICIs in the neoadjuvant therapy of patients with early stage NSCLC are emerging. Eligible subjects were treatment naïve patients with stage IB, II, and resectable IIIA NSCLC. Patients received three cycles of neoadjuvant chemotherapy with four doses of avelumab every 2 weeks. Patients with squamous cell cancer received cisplatin or carboplat

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Negative / Null Result ReportOpen accessMedicine

Long-term results of a phase II study with neoadjuvant docetaxel chemotherapy and complete androgen blockade in locally advanced and high-risk prostate cancer

Mark Thalgott, Thomas Horn, Matthias Heck et al. · 2014 · Journal of Hematology & Oncology

BACKGROUND: Patients with locally advanced and high-risk prostate cancer (LAPC) are prone to experience biochemical recurrence despite radical prostatectomy (RP). We evaluated feasibility, safety and activity of a neoadjuvant chemohormonal therapy (NCHT) with 3-weekly full dose docetaxel and complete androgen blockade (CAB) in locally advanced and high-risk prostate cancer patients (LAPC) undergoing RP. METHODS: Patients (n = 30) were selected by Kattans' preoperative score and received trimestral buserelin 9,45 mg, bicalutamide 50 mg/day and 3 cycles docetaxel (75 mg/m²) followed by RP. Prima

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Negative / Null Result ReportOpen accessMedicine

Lack of Associations between Female Hormone Levels and Visuospatial Working Memory, Divided Attention and Cognitive Bias across Two Consecutive Menstrual Cycles

Brigitte Leeners, Tillmann H. C. Krüger, Kirsten Geraedts et al. · 2017 · Frontiers in Behavioral Neuroscience

Background: Interpretation of observational studies on associations between prefrontal cognitive functioning and hormone levels across the female menstrual cycle is complicated due to small sample sizes and poor replicability. Methods: This observational multisite study comprised data of n=88 menstruating women from Hannover, Germany, and Zurich, Switzerland, assessed during a first cycle and n=68 re-assessed during a second cycle to rule out practice effects and false-positive chance findings. We assessed visuospatial working memory, attention, cognitive bias and hormone levels at four consec

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Negative / Null Result ReportOpen accessMedicine

A Randomized Placebo-Controlled Trial of the Anti-Nerve Growth Factor Antibody Tanezumab in Subjects With Cancer Pain Due to Bone Metastasis

Marie Fallon, Maciej Sopata, Erika Dragon et al. · 2023 · The Oncologist

BACKGROUND: This phase III, randomized, double-blind, placebo-controlled, parallel-group study assessed the efficacy and safety of tanezumab in subjects with cancer pain predominantly due to bone metastasis receiving background opioid…

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Negative / Null Result ReportOpen accessMedicine

Generation and validation of ActiGraph GT3X+ accelerometer cut-points for assessing physical activity intensity in older adults. The OUTDOOR ACTIVE validation study

Karin Bammann, Nicola K. Thomson, Birte Marie Albrecht et al. · 2021 · PLoS ONE

The study of physical activity in older adults is becoming more and more relevant. For evaluation of physical activity recommendations, intensity-specific accelerometer cut-points are utilized. However, research on accelerometer cut-points for older adults is still scarce. The aim of the study was to generate placement-specific cut-points of ActiGraph GT3X+ activity counts and raw measures of acceleration to determine physical activity intensity in older adults. A further aim was to compare the validity of the generated cut-points for a range of different physical activities. The study was a s

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Negative / Null Result ReportMedicine

Delirium in the intensive care setting: A reevaluation of the validity of the CAM–ICU and ICDSC versus the DSM–IV–TR in determining a diagnosis of delirium as part of the daily clinical routine

Soenke Böettger, David García Núñez, Rafael Meyer et al. · 2017 · Palliative & Supportive Care

BACKGROUND: In the intensive care setting, delirium is a common occurrence that comes with subsequent adversities. Therefore, several instruments have been developed to screen for and detect delirium. Their validity and psychometric…

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Failed Experiment ReportOpen accessMedicine

Protection Against Staphylococcus aureus by Antibody to the Polyglycerolphosphate Backbone of Heterologous Lipoteichoic Acid

Christian Theilacker, Andrea Kropec, Felix Hammer et al. · 2012 · The Journal of Infectious Diseases

Type 1 lipoteichoic acid (LTA) is present in many clinically important gram-positive bacteria, including enterococci, streptococci, and staphylococci, and antibodies against LTA have been shown to opsonize nonencapsulated Enterococcus…

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Negative / Null Result ReportOpen accessMedicine

A Novel Bat Herpesvirus Encodes Homologues of Major Histocompatibility Complex Classes I and II, C-Type Lectin, and a Unique Family of Immune-Related Genes

Huajun Zhang, Shawn Todd, Mary Tachedjian et al. · 2012 · Journal of Virology

Herpesviruses or herpesviral sequences have been identified in various bat species. Here, we report the isolation, cell tropism, and complete genome sequence of a novel betaherpesvirus from the bat Miniopterus schreibersii (MsHV). In…

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Negative / Null Result ReportOpen accessMedicine

A New Orbivirus Isolated from Mosquitoes in North-Western Australia Shows Antigenic and Genetic Similarity to Corriparta Virus but Does Not Replicate in Vertebrate Cells

Jessica J. Harrison, David Warrilow, Breeanna J. McLean et al. · 2016 · Viruses

The discovery and characterisation of new mosquito-borne viruses provides valuable information on the biodiversity of vector-borne viruses and important insights into their evolution. In this study, a broad-spectrum virus screening system, based on the detection of long double-stranded RNA in inoculated cell cultures, was used to investigate the presence of novel viruses in mosquito populations of northern Australia. We detected and isolated a new virus (tentatively named Parry's Lagoon virus, PLV) from Culex annulirostris, Culex pullus, Mansonia uniformis and Aedes normanensis mosquitoes that

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Negative / Null Result ReportOpen accessMedicine

Inhibitory effect of novel iron chelator, 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) and green tea extract on growth of Plasmodium falciparum

Phitsinee Thipubon, Chairat Uthaipibull, Sumalee Kamchonwongpaisan et al. · 2015 · Malaria Journal

BACKGROUND: Iron is an essential micronutrient required by all living organisms including malaria parasites (Plasmodium spp.) for many biochemical reactions, especially growth and multiplication processes. Therefore, malaria parasite needs to take up the iron from outside or/and inside the parasitized red blood cells (PRBC). Iron chelators are widely used for the treatment of thalassaemia-related iron overload and also inhibit parasite growth at levels that are non-toxic to mammalian cells. METHODS: Inhibitory effect of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) and green

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Negative / Null Result ReportOpen accessMedicine

Pre- and post-operative anti-PD-L1 plus anti-angiogenic therapies in mouse breast or renal cancer models of micro- or macro-metastatic disease

Florence T.H. Wu, Ping Xu, Annabelle Chow et al. · 2018 · British Journal of Cancer

There are phase 3 clinical trials underway evaluating anti-PD-L1 antibodies as adjuvant (postoperative) monotherapies for resectable renal cell carcinoma (RCC) and triple-negative breast cancer (TNBC); in combination with antiangiogenic VEGF/VEGFR2 inhibitors (e.g., bevacizumab and sunitinib) for metastatic RCC; and in combination with chemotherapeutics as neoadjuvant (preoperative) therapies for resectable TNBC. This study investigated these and similar clinically relevant drug combinations in highly translational preclinical models of micro- and macro-metastatic disease that spontaneously de

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Negative / Null Result ReportOpen accessMedicine

SAKK 24/09: safety and tolerability of bevacizumab plus paclitaxel vs. bevacizumab plus metronomic cyclophosphamide and capecitabine as first-line therapy in patients with HER2-negative advanced stage breast cancer - a multicenter, randomized phase III trial

Christoph Rochlitz, Martin Bigler, Roger von Moos et al. · 2016 · BMC Cancer

BACKGROUND: Adding bevacizumab to chemotherapy improves response rates and progression-free survival (PFS) in metastatic breast cancer (mBC). We aimed to demonstrate decreased toxicity with metronomic chemotherapy/bevacizumab compared with paclitaxel/bevacizumab. METHODS: This multicenter, randomized phase III trial compared bevacizumab with either paclitaxel (arm A) or daily oral capecitabine-cyclophosphamide (arm B) as first-line treatment in patients with HER2-negative advanced breast cancer. The primary endpoint was the incidence of selected grade 3-5 adverse events (AE) including: febrile

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Negative / Null Result ReportOpen accessMedicine

Initial Clinical Experience with a Modulated Holmium Laser Pulse—Moses Technology: Does It Enhance Laser Lithotripsy Efficacy?

Michael Mullerad, Jonatan R. A. Aguinaga, Tareq Aro et al. · 2017 · Rambam Maimonides Medical Journal

OBJECTIVE: High-power Holmium Laser (120H) has a unique modulated pulse mode, Moses™ technology. Moses technology modulates the laser pulse to separate the water (vapor bubble), then deliver the remaining energy through the bubble. Proprietary laser fibers were designed for the Moses technology. Our aim was to compare stone lithotripsy with and without the Moses technology. METHODS: We designed a questionnaire for the urologist to fill immediately after each ureteroscopy in which the Lumenis 120H was used. We compared procedures with (n=23) and without (n=11) the use of Moses technology. Surge

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Negative / Null Result ReportOpen accessMedicine

A segregation index combining phenotypic (clinical characteristics) and genotypic (gene expression) biomarkers from a urine sample to triage out patients presenting with hematuria who have a low probability of urothelial carcinoma

L. Kavalieris, P.J. O’Sullivan, James M. Suttie et al. · 2015 · BMC Urology

BACKGROUND: Hematuria can be symptomatic of urothelial carcinoma (UC) and ruling out patients with benign causes during primary evaluation is challenging. Patients with hematuria undergoing urological work-ups place significant clinical and financial burdens on healthcare systems. Current clinical evaluation involves processes that individually lack the sensitivity for accurate determination of UC. Algorithms and nomograms combining genotypic and phenotypic variables have largely focused on cancer detection and failed to improve performance. This study aimed to develop and validate a model inc

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Negative / Null Result ReportOpen accessMedicine

Islatravir Has a High Barrier to Resistance and Exhibits a Differentiated Resistance Profile from Approved Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Tracy L. Diamond, Winnie Ngo, Min Xu et al. · 2022 · Antimicrobial Agents and Chemotherapy

Islatravir (ISL) is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) that inhibits human immunodeficiency virus (HIV) reverse transcription by blocking reverse transcriptase (RT) translocation on the primer:template. ISL…

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Negative / Null Result ReportOpen accessMedicine

Prerequisites for the acquisition of mammalian pathogenicity by influenza A virus with a prototypic avian PB2 gene

Chung-Young Lee, Se-Hee An, Il Hwan Kim et al. · 2017 · Scientific Reports

The polymerase of avian influenza A virus (AIV) is a heterotrimer composed of PB2, PB1, and PA. PB2 plays a role in overcoming the host barrier; however, the genetic prerequisites for avian PB2 to acquire mammalian pathogenic mutations have not been well elucidated. Previously, we identified a prototypic avian PB2 that conferred non-replicative and non-pathogenic traits to a PR8-derived recombinant virus when it was used to infect mice. Here, we demonstrated that key amino acid mutations (I66M, I109V, and I133V, collectively referred to as MVV) of this prototypic avian PB2 increase the replica

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Negative / Null Result ReportOpen accessMedicine

A risk calculator to predict adult attention-deficit/hyperactivity disorder: generation and external validation in three birth cohorts and one clinical sample

Arthur Caye, Jessica Agnew‐Blais, Louise Arseneault et al. · 2019 · Epidemiology and Psychiatric Sciences

AIM: Few personalised medicine investigations have been conducted for mental health. We aimed to generate and validate a risk tool that predicts adult attention-deficit/hyperactivity disorder (ADHD). METHODS: Using logistic regression models, we generated a risk tool in a representative population cohort (ALSPAC - UK, 5113 participants, followed from birth to age 17) using childhood clinical and sociodemographic data with internal validation. Predictors included sex, socioeconomic status, single-parent family, ADHD symptoms, comorbid disruptive disorders, childhood maltreatment, ADHD symptoms,

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Negative / Null Result ReportOpen accessMedicine

Adjuvant radiotherapy for completely resected stage 2 thymoma

Abigail T. Berman, Leslie A. Litzky, Virginia A. LiVolsi et al. · 2011 · Cancer

BACKGROUND: The clinical benefit of postoperative mediastinal radiation for completely resected Masaoka stage 2 thymoma remains controversial. Due to its indolent nature and infrequent recurrences, no study has definitively determined the…

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Negative / Null Result ReportOpen accessMedicine

Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer

Yan Sun, Ying Cheng, Xuezhi Hao et al. · 2016 · BMC Cancer

BACKGROUND: Extensive-disease small-cell lung cancer (ED-SCLC) is characterized by rapid progression and relapse, despite high initial response rates to chemotherapy. The primary objective of this trial was to demonstrate the non-inferiority of amrubicin and cisplatin (AP) combination therapy compared with the standard first-line regimen of etoposide and cisplatin (EP) for previously untreated ED-SCLC in a Chinese population. When non-inferiority was verified, the objective was switched from non-inferiority to superiority. METHODS: From June 2008 to July 2010, 300 patients were enrolled and ra

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Negative / Null Result ReportOpen accessMedicine

Myxomavirus-Derived Serpin Prolongs Survival and Reduces Inflammation and Hemorrhage in an Unrelated Lethal Mouse Viral Infection

Hao Chen, Donghang Zheng, Jeff Abbott et al. · 2013 · Antimicrobial Agents and Chemotherapy

Lethal viral infections produce widespread inflammation with vascular leak, clotting, and bleeding (disseminated intravascular coagulation [DIC]), organ failure, and high mortality. Serine proteases in clot-forming (thrombotic) and…

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Negative / Null Result ReportMedicine

LRP1B, BRD2 and CACNA1D : New Candidate Genes in Fetal Metabolic Programming of Newborns Exposed to Maternal Hyperglycemia

Andrée-Anne Houde, Stéphanie-May Ruchat, Catherine Allard et al. · 2015 · Epigenomics

AIM: To assess the associations between gestational diabetes mellitus (GDM) and DNA methylation levels at genes related to energy metabolism. PATIENTS & METHODS: Ten loci were selected from our recent epigenome-wide association study on…

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Negative / Null Result ReportOpen accessMedicine

High-Dose Inhaled Nitric Oxide in Acute Hypoxemic Respiratory Failure Due to COVID-19: A Multicenter Phase II Trial

Raffaele Di Fenza, Naman S. Shetty, Stefano Gianni et al. · 2023 · American Journal of Respiratory and Critical Care Medicine

Abstract Rationale The effects of high-dose inhaled nitric oxide on hypoxemia in coronavirus disease (COVID-19) acute respiratory failure are unknown. Objectives The primary outcome was the change in arterial oxygenation (PaO2/Fi O2) at 48…

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Negative / Null Result ReportOpen accessMedicine

Patients with carotid atherosclerosis who underwent or did not undergo carotid endarterectomy: outcome on mood, cognition and quality of life

Mauro Giovanni Carta, Maria Efisia Lecca, Luca Saba et al. · 2015 · BMC Psychiatry

BACKGROUND: To compare the six-month outcome on mood, cognition and quality of life (QoL) in patients with severe carotid atherosclerosis (CA) who underwent carotid endarterectomy (CEA) with subjects who refused treatment. METHODS: Cohort study on consecutive inpatients with CA (stenosis ≥ 50 %) (N = 46; age 72.56 ± 7.26; male 65.2 %). Intervention cohort: subjects who decided to undergo CEA (N = 35); Control cohort patients who refused CEA (N = 11). DSM-IV-Psychiatric diagnosis made by clinicians using interviews, QoL measured by Short Form Health Survey (SF-12); cognitive performance by WAIS

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Negative / Null Result ReportOpen accessMedicine

TMEM41B and VMP1 modulate cellular lipid and energy metabolism for facilitating dengue virus infection

Meisam Yousefi, Wai Suet Lee, Biaoguo Yan et al. · 2022 · PLoS Pathogens

Transmembrane Protein 41B (TMEM41B) and Vacuole Membrane Protein 1 (VMP1) are two ER-associated lipid scramblases that play a role in autophagosome formation and cellular lipid metabolism. TMEM41B is also a recently validated host factor required by flaviviruses and coronaviruses. However, the exact underlying mechanism of TMEM41B in promoting viral infections remains an open question. Here, we validated that both TMEM41B and VMP1 are essential host dependency factors for all four serotypes of dengue virus (DENV) and human coronavirus OC43 (HCoV-OC43), but not chikungunya virus (CHIKV). While

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Negative / Null Result ReportOpen accessMedicine

Loss of Protease Dimerization Inhibition Activity of Darunavir Is Associated with the Acquisition of Resistance to Darunavir by HIV-1

Yasuhiro Koh, Manabu Aoki, Matthew Danish et al. · 2011 · Journal of Virology

Dimerization of HIV protease is essential for the acquisition of protease's proteolytic activity. We previously identified a group of HIV protease dimerization inhibitors, including darunavir (DRV). In the present work, we examine whether…

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