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Browse the failure-mode index

12,240 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

Efficacy and safety of combination behavioral activation for smoking cessation and varenicline for treating tobacco dependence among individuals with current or past major depressive disorder: A 2 × 2 factorial, randomized, placebo‐controlled trial

Brian Hitsman, George D. Papandonatos, Jackie K. Gollan et al. · 2023 · Addiction

BACKGROUND AND AIMS: Treatment of depression-related psychological factors related to smoking behavior may improve rates of cessation among adults with major depressive disorder (MDD). This study measured the efficacy and safety of 12…

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Negative / Null Result ReportOpen accessMedicine

Combining Structural and Vascular Parameters to Discriminate Among Glaucoma Patients, Glaucoma Suspects, and Healthy Subjects

Alessandro Rabiolo, Federico Fantaguzzi, Riccardo Sacconi et al. · 2021 · Translational Vision Science & Technology

Purpose: Compare the ability of peripapillary and macular structural parameters, vascular parameters, and their integration to discriminate among glaucoma, suspected glaucoma (GS), and healthy controls (HCs). Methods: In this study, 196…

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Negative / Null Result ReportOpen accessMedicine

Ocular Surface Ion Transport and Dry Eye Disease

Ethan S. Lindgren, Onur Çil, A. S. Verkman et al. · 2022 · Current Ophthalmology Reports

Purpose of Review: To review the role of ocular surface epithelial (corneal and conjunctival) ion transporters in the pathogenesis and treatment of dry eye disease (DED). Recent Findings: Currently, anti-inflammatory agents are the mainstay of DED treatment, though there are several agents in development that target ion transport proteins on the ocular surface, acting by pro-secretory or anti-absorptive mechanisms to increase the tear fluid Film volume. Activation or inhibition of selected ion transporters can alter tear fluid osmolality, driving water transport onto the ocular surface via osm

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Negative / Null Result ReportOpen accessMedicine

Rodent Models of Alzheimer’s Disease: Past Misconceptions and Future Prospects

Helen M Collins, Susan A. Greenfield · 2024 · International Journal of Molecular Sciences

Alzheimer's disease (AD) is a progressive neurodegenerative disease with no effective treatments, not least due to the lack of authentic animal models. Typically, rodent models recapitulate the effects but not causes of AD, such as cholinergic neuron loss: lesioning of cholinergic neurons mimics the cognitive decline reminiscent of AD but not its neuropathology. Alternative models rely on the overexpression of genes associated with familial AD, such as amyloid precursor protein, or have genetically amplified expression of mutant tau. Yet transgenic rodent models poorly replicate the neuropatho

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Negative / Null Result ReportOpen accessMedicine

Impact of Pancreatic Resection on Survival in Locally Advanced Resectable Gastric Cancer

Shih-Chun Chang, Chi-Ming Tang, Puo‐Hsien Le et al. · 2021 · Cancers

Whether gastric adenocarcinoma (GC) patients with adjacent organ invasion (T4b) benefit from aggressive surgery involving pancreatic resection (PR) remains unclear. This study aimed to clarify the impact of PR on survival in patients with locally advanced resectable GC. Between 1995 and 2017, patients with locally advanced GC undergoing radical-intent gastrectomy with and without PR were enrolled and stratified into four groups: group 1 (G1), pT4b without pancreatic resection (PR); group 2 (G2), pT4b with PR; group 3 (G3), positive duodenal margins without Whipple’s operation; and group 4 (G4)

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Negative / Null Result ReportOpen accessMedicine

Induction TPF followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locally advanced hypopharyngeal cancer: a preliminary analysis of a randomized phase 2 trial

Xi Luo, Xiaodong Huang, Jingwei Luo et al. · 2022 · BMC Cancer

PURPOSE: Concurrent chemoradiotherapy (CCRT) is a standard treatment choice for locally advanced hypopharyngeal carcinoma. The aim of this study was to investigate whether induction chemotherapy (IC) followed by CCRT is superior to CCRT alone to treat locally advanced hypopharyngeal carcinoma. METHODS AND MATERIALS: Patients (n = 142) were randomized to receive two cycles of paclitaxel/cisplatin/5-fluorouracil (TPF) IC followed by CCRT or CCRT alone. The primary end point was overall survival (OS). The secondary end points included the larynx-preservation rate, progression-free survival (PFS),

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Negative / Null Result ReportOpen accessMedicine

Genetic stability of RSV-F expression and the restricted growth phenotype of a live attenuated PIV3 vectored RSV vaccine candidate (MEDI-534) following restrictive growth in human lung cells

Christine L. Nelson, Roderick S. Tang, Elizabeth A. Stillman · 2013 · Vaccine

MEDI-534 is the first live, attenuated and vectored respiratory syncytial virus (RSV) vaccine to be evaluated in seronegative children. It consists of a bovine/human parainfluenza virus type 3 (PIV3) backbone with the RSV fusion…

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Negative / Null Result ReportOpen accessMedicine

Selective internal radiation therapy (SIRT) for hepatocellular carcinoma (HCC): informing clinical practice for multidisciplinary teams in England

Helen L. Reeves, John Reicher, Georgia Priona et al. · 2022 · Frontline Gastroenterology

Objective: Hepatocellular carcinoma (HCC) deaths are rising alarmingly. Many patients are unsuitable for available therapies. Poor response rates further hamper outcomes for those that are. Selective internal radiation therapy (SIRT) offers hope, although which patients benefit over standard approaches remains unclear. Design/method: As a quality/service improvement, we audited consecutive patients treated with SIRT (2015-2020) by the Newcastle upon Tyne Hospitals National Health Service Foundation Trust HCC multidisciplinary team. Indications, Barcelona clinic liver cancer (BCLC) stage, treat

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Negative / Null Result ReportOpen accessMedicine

Genetic predictors of GLP1 receptor agonist weight loss and side effects

Qiaojuan Jane Su, James R. Ashenhurst, Wanwan Xu et al. · 2026 · Nature

The development of glucagon-like peptide 1 (GLP1) receptor agonists, including semaglutide and tirzepatide, has transformed the clinical management of overweight and obesity. However, substantial inter-person variability exists in both…

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Negative / Null Result ReportOpen accessMedicine

Tirzepatide on obstructive sleep apnea-related cardiometabolic risk: secondary outcomes of the SURMOUNT-OSA randomized trial

Atul Malhotra, R GRUNSTEIN, Ali Azarbarzin et al. · 2026 · Nature Medicine

Obstructive sleep apnea (OSA) is associated with obesity and cardiovascular risk. The SURMOUNT-OSA master protocol comprised two, 52-week, randomized, double-blind, placebo-controlled phase 3 studies (study 1 and study 2) and demonstrated…

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Negative / Null Result ReportOpen accessMedicine

Treat-to-Target Urate-Lowering Treatment and Cardiovascular Outcomes in Patients With Gout

Edoardo Cipolletta, Tatiana Zverkova Sandström, D. Rozza et al. · 2026 · JAMA Internal Medicine

Importance: Gout is associated with increased cardiovascular risk. Whether achieving a target serum urate level lower than 6 mg/dL with urate-lowering treatment (ULT) would reduce cardiovascular risk in patients with gout is unknown. Objectives: To evaluate the association between achieving a serum urate treatment target lower than 6 mg/dL and cardiovascular events among patients with gout who were newly prescribed ULT. Design, Setting, and Participants: This new-user cohort study using emulated target trial framework with up to 5-year follow-up was performed using primary care data from the C

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Negative / Null Result ReportOpen accessMedicine

Central adiposity indices and inflammatory markers mediate the association between life’s crucial 9 and periodontitis in US adults

Jia-Jie Guo, Qi-Qi Hang, Ting Xu et al. · 2025 · Lipids in Health and Disease

BACKGROUND: Periodontitis, a chronic inflammatory disease, is closely linked to cardiovascular health. While Life's Essential 8 (LE8) evaluates cardiovascular metrics, recent recommendations suggest incorporating psychological health (PHQ-9) to form Life's Crucial 9 (LC9). However, evidence regarding the utility of LC9 in periodontal disease remains limited. METHODS: We analyzed data from 7,674 adults in the 2009-2014 NHANES cycles. LC9 scores were calculated by integrating LE8 and PHQ-9 metrics, then categorized into quartiles. The association between LC9 and periodontitis was examined using

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Negative / Null Result ReportOpen accessMedicine

Parents perception of weight status of Mexican preschool children using different tools

M.a Cruces Souto-Gallardo, Arturo Jiménez–Cruz, Montserrat Bacardí‐Gascón · 2026 · Archivos Latinoamericanos de Nutrición

The aim of this study was to evaluate the ability of parents to estimate the weight status of preschool children attending the Instituto Mexicano del Seguro Social (IMSS) day-care centers using three different tools. A total of 100…

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Replication FailureOpen accessMedicine

Long-Term Outcomes of Left Bundle-Branch Pacing vs Biventricular Pacing in Heart Failure

Xueying Chen, Xi Liu, Ruogu Li et al. · 2026 · JAMA Cardiology

Importance: Left bundle-branch pacing (LBBP) has been proposed as an alternative to biventricular pacing (BiVP) for patients with heart failure with left bundle-branch block (LBBB). However, robust clinical evidence from randomized clinical trials is lacking. Objective: To evaluate the long-term clinical outcomes of LBBP and BiVP. Design, Setting, and Participants: This multicenter, prospective, randomized clinical trial enrolled 200 patients at 6 centers in China with a left ventricular ejection fraction (LVEF) of 35% or less and LBBB from October 2020 to March 2022. This study was took place

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Negative / Null Result ReportOpen accessMedicine

The combined risk effect among BIN1, CLU, and APOE genes in Alzheimer’s disease

Lígia Ramos dos Santos, Jucimara Ferreira Figueiredo Almeida, Lúcia Helena Sagrillo Pimassoni et al. · 2019 · Genetics and Molecular Biology

Genome-wide associations studies (GWAS) are detecting new variants associated with late-onset of Alzheimer's disease (LOAD), a multifactorial neurodegenerative disorder. The variants rs744373 BIN1, rs11136000 CLU and rs3764650 ABCA7 uncovered by GWAS led to different AD pathways, such as metabolism, trafficking and endocytosis of lipids and inflammation. However, most of the association studies did not replicate these variants with significance. This could be due to a small power effect evident when these variants are tested independently with LOAD. Therefore, we aimed to investigate whether t

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Negative / Null Result ReportOpen accessMedicine

A human tumor-immune organoid model of glioblastoma

Shivani Baisiwala, Elisa Fazzari, Matthew Li et al. · 2026 · Cell Reports

A major obstacle to identifying effective therapies for the aggressive brain tumor glioblastoma is the lack of human-specific, immunocompetent models that reflect the human tumor microenvironment. To address this, we developed the…

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Negative / Null Result ReportOpen accessMedicine

Serum Albumin Level at Intensive Care Unit Admission and Delirium Duration and Severity in Critically Ill Adults

Rosalyn Chi, Anthony J. Perkins, Yara Khalifeh et al. · 2024 · American Journal of Critical Care

BACKGROUND: Hypoalbuminemia has been associated with an increased risk of in-hospital delirium. However, the relationship between serum albumin levels and the duration and severity of delirium is not well defined. OBJECTIVE: To investigate…

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Negative / Null Result ReportMedicine

Should we use automated external defibrillators in hospital wards?

Mélissa De Regge, Koenraad G. Monsieurs, K. Vandewoude et al. · 2012 · PubMed

Automated external defibrillators (AEDs) have shown to improve survival after cardiopulmonary arrest (CPA) in many, but not all clinical settings. A recent study reported that the use of AEDs in-hospital did not improve survival. The…

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Negative / Null Result ReportOpen accessMedicine

The Effects of Disease-Modifying Antirheumatic Drugs on Cardiovascular Risk in Inflammatory Joint Diseases: Current Evidence and Uncertainties

Olena Garmish, Svitlana Smiyan, Fedir Hladkykh et al. · 2025 · Vascular Health and Risk Management

Patients with inflammatory joint diseases, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, have an elevated risk of cardiovascular complications due to systemic inflammation, immune-mediated endothelial…

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Negative / Null Result ReportOpen accessMedicine

Molecular mechanisms underlying the abscopal effect induced by radiotherapy and its synergistic translational potential with immunotherapy

Xinyi Chen, Mu Yang, Yongbiao Huang et al. · 2025 · Therapeutic Advances in Medical Oncology

Abscopal immunity—the regression of distant, non-irradiated lesions after localized radiotherapy (RT)—signals conversion of focal DNA damage into systemic antitumor immunity. This review advances a unifying three-stage…

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Negative / Null Result ReportOpen accessMedicine

Gut Microbiota Dysbiosis in Endometriosis: A Potential Link to Inflammation and Disease Progression

Alexandra Irma Gabriela Bauşic, Francesca Scurtu, Andrei Manu et al. · 2025 · International Journal of Molecular Sciences

Endometriosis is a complex gynaecological disorder characterised by the presence of endometrial-like tissue outside the uterus, leading to chronic inflammation, pain, and infertility. Recent research suggests that gut microbiota may play a crucial role in the pathogenesis and progression of endometriosis by modulating immune responses and oestrogen metabolism. This study investigates the intestinal microbiota composition in women with endometriosis and its potential as a disease diagnosis and severity biomarker. Stool samples from nine patients diagnosed with endometriosis were analysed using

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Negative / Null Result ReportOpen accessMedicine

Leveraging radiotherapy to improve immunotherapy outcomes: rationale, progress and research priorities

Faith Hartley, Martin A. Ebert, Alistair Cook · 2025 · Clinical & Translational Immunology

The most successful immunotherapies for solid malignancies to date, immune checkpoint inhibitors, target the essential role of T cells in antitumor immunity. However, T-cell dysfunction presents a major hindrance to treatment efficacy, warranting research into combined treatment strategies for improving outcomes. The use of radiotherapy for this purpose has garnered much interest. Preclinical study has established that radiotherapy activates various immune mechanisms to improve T-cell activation, localisation and function within tumors, which improves response to immune checkpoint inhibitors.

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Negative / Null Result ReportOpen accessMedicine

Five‐Year Unified Risk Prediction Model for Gastric and Esophageal Cancer Based on Nationwide Health Check‐Up Data in Japan: J‐GESS Score

Kenta Watanabe, Sho Fukuda, Dai Kubota et al. · 2026 · Journal of Gastroenterology and Hepatology

BACKGROUND AND AIM: In Japan, gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC) account for nearly all fatal upper gastrointestinal malignancies. A unified model that simultaneously predicts the incidence of these two…

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Negative / Null Result ReportMedicine

Different organ-specific response to nivolumab to determine the survival outcome of patients with advanced hepatocellular carcinoma (aHCC).

Han Sang Kim, Jung Yong Hong, Jaekyung Cheon et al. · 2020 · Journal of Clinical Oncology

4584 Background: Previously, two phase III clinical trials of immune checkpoint inhibitors (ICI) failed to meet their primary endpoints, leading to doubts regarding the clinical activity of ICI monotherapy in patients with aHCC. Here, we…

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Negative / Null Result ReportOpen accessMedicine

Exercise blood pressure relative to fitness and cardiovascular outcomes: the EXERTION study

Martin G Schultz, Petr Otahal, Philip Roberts-Thomson et al. · 2025 · European Heart Journal

BACKGROUND AND AIMS: A hypertensive response to exercise is independently associated with cardiovascular disease (CVD), but clinical interpretation may be confounded by aerobic capacity (fitness). The aim of this study was to determine the relationship between exercise blood pressure (BP) relative to fitness and CVD events. METHODS: Clinical exercise test records were analysed from 12 743 people (aged 53 ± 13 years, 60% male) who completed a standard exercise stress test (Bruce treadmill protocol, stages 1-4) at six Australian hospitals. Records were linked to administrative datasets (hospital

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Negative / Null Result ReportOpen accessMedicine

Rotational Projection Errors in Coronal Knee Alignment on Weight-Bearing Whole-Leg Radiographs: A 3D CT Reference Across CPAK Morphotypes

Igor Strahovnik, Andrej Strahovnik, Samo K. Fokter · 2025 · Bioengineering

Whole-leg radiographs (WLRs) are widely used to assess coronal alignment before total knee arthroplasty (TKA), but may be inaccurate in patients with atypical morphotypes or malrotation. This study evaluated the discrepancy between WLR and 3D computed tomography (CT) scans across coronal plane alignment of the knee (CPAK) morphotypes and introduced a novel projection index—the femoral notch projection ratio (FNPR). In CPAK III knees, 19% of cases exceeded a clinically relevant threshold (>3° difference), prompting investigation of underlying projection factors. In 187 knees, coronal angles—

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Negative / Null Result ReportOpen accessMedicine

Impact of Preexisting Hepatitis C Virus Genotype 6 NS3, NS5A, and NS5B Polymorphisms on theIn VitroPotency of Direct-Acting Antiviral Agents

Fiona McPhee, Joseph Ueland, Vincent Vellucci et al. · 2019 · Antimicrobial Agents and Chemotherapy

[tested DAAs] of >5,000 nM) and were detected in evaluated GT-6b and -6f sequences. NS5A-L28A-R30A, observed in GT-6r, did not replicate. In conclusion, HCV GT-6b, GT-6f, and GT-6r sequences harbored highly resistant RASs to all evaluated…

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Negative / Null Result ReportOpen accessMedicine

Conduction System vs Biventricular Pacing in Heart Failure

André Zimerman, Alexander Dal Forno, Luis E. Rohde et al. · 2026 · JAMA Cardiology

Importance: Conduction system pacing (CSP) is a promising and potentially cost-effective alternative to biventricular pacing (BiVP) in patients with heart failure with reduced ejection fraction (HFrEF) and left bundle-branch block (LBBB), but its impact on heart failure (HF) outcomes remains uncertain. Objective: To compare CSP vs BiVP on an HF-related outcome in patients with HFrEF and LBBB. Design, Setting, and Participants: PhysioSync-HF (Conduction System Pacing Versus Biventricular Resynchronization in Patients With Chronic Heart Failure) was an investigator-initiated, multicenter, noninf

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Negative / Null Result ReportOpen accessMedicine

Still a Place for Metoclopramide as a Prokinetic Drug in Critically Ill Patients?

Arthur R. H. van Zanten, Y. G. Van Der Meer, Willem A. Venhuizen et al. · 2015 · Journal of Parenteral and Enteral Nutrition

Neurologic adverse reactions, including extrapyramidal disorders, dyskinesia, dystonia, convulsions, hypertonia, and tremors.4 The reported occurrence of tardive dyskinesia ranges from <0.01%–23%.5 High occurrence is attributed to chronic…

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