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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 ReportMedicine

A Combination of Impulsivity Subdomains Predict Alcohol Intoxication Frequency

Laura O’Halloran, Brian Pennie, Lee Jollans et al. · 2018 · Alcoholism Clinical and Experimental Research

BACKGROUND: Impulsivity, broadly characterized as the tendency to act prematurely without foresight, is linked to alcohol misuse in college students. However, impulsivity is a multidimensional construct and different subdomains likely…

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Negative / Null Result ReportOpen accessMedicine

Deep brain stimulation for psychiatric disorders: role of imaging in identifying/confirming DBS targets, predicting, and optimizing outcome and unravelling mechanisms of action

Dejan Georgiev, Harith Akram, Marjan Jahanshahi · 2021 · Psychoradiology

Following the established application of deep brain stimulation (DBS) in the treatment of movement disorders, new non-neurological indications have emerged, such as for obsessive-compulsive disorders, major depressive disorder, dementia, Gilles de la Tourette Syndrome, anorexia nervosa, and addictions. As DBS is a network modulation surgical treatment, the development of DBS for both neurological and psychiatric disorders has been partly driven by advances in neuroimaging, which has helped explain the brain networks implicated. Advances in magnetic resonance imaging connectivity and electrophy

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Negative / Null Result ReportOpen accessMedicine

Emerging biologic frontiers for Sjogren’s syndrome: Unveiling novel approaches with emphasis on extra glandular pathology

Xiao Li, Maierhaba Maitiyaer, Qing Tan et al. · 2024 · Frontiers in Pharmacology

Primary Sjögren's Syndrome (pSS) is a complex autoimmune disorder characterized by exocrine gland dysfunction, leading to dry eyes and mouth. Despite growing interest in biologic therapies for pSS, FDA approval has proven challenging due to trial complications. This review addresses the absence of a molecular-target-based approach to biologic therapy development and highlights novel research on drug targets and clinical trials. A literature search identified potential pSS treatment targets and recent advances in molecular understanding. Overlooking extraglandular symptoms like fatigue and depr

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Negative / Null Result ReportMedicine

Is the Short Form of the Mini-Mental State Examination (MMSE) a better screening instrument for dementia in older primary care patients than the original MMSE? Results of the German study on ageing, cognition, and dementia in primary care patients (AgeCoDe).

Janine Stein, Melanie Luppa, Hanna Kaduszkiewicz et al. · 2015 · Psychological Assessment

The aim of the study was to investigate the psychometric properties of a Short Form of the Mini-Mental State Examination (SMMSE) for the screening of dementia in older primary care patients. Data were obtained from a large longitudinal…

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Negative / Null Result ReportOpen accessMedicine

Is There Significant Difference between Digital and Glass Mercury Thermometer?

Hadgu Gerensea, Rajalakshmi Murugan · 2016 · Advances in Nursing

Background . Children’s decisions concerning investigation and treatment may be based on the results of temperature alone. Although the accuracy of axillary temperature measurement is affected by a number of factors, device dwell time and device type are common. Objective . Compare body temperature between glass mercury thermometer (GMT) and digital thermometer (DT). Method . Comparative descriptive study was used. A total of 101 samples were taken with convenient sampling technique, but 98 were analyzed. Statistical significance (p<0.01) and clinical significance (MD≥0.2°C) were used in th

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Negative / Null Result ReportOpen accessMedicine

Rescue of Infectious Rotavirus Reassortants by a Reverse Genetics System Is Restricted by the Receptor-Binding Region of VP4

Alexander Falkenhagen, Marno Huyzers, Alberdina A. van Dijk et al. · 2021 · Viruses

The rotavirus species A (RVA) capsid contains the spike protein VP4, which interacts with VP6 and VP7 and is involved in cellular receptor binding. The capsid encloses the genome consisting of eleven dsRNA segments. Reassortment events can result in novel strains with changed properties. Using a plasmid-based reverse genetics system based on simian RVA strain SA11, we previously showed that the rescue of viable reassortants containing a heterologous VP4-encoding genome segment was strain-dependent. In order to unravel the reasons for the reassortment restrictions, we designed here a series of

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Negative / Null Result ReportOpen accessMedicine

Rise of precision medicine: can it deliver on its promise in IBD?

Stefan Schreiber, Konrad Aden, Florian Tran et al. · 2025 · Gut

The clinical and molecular heterogeneity of IBD—both between patients and within the same individual over time—continues to pose a significant challenge to the implementation of truly personalised treatment strategies. Unlike oncology,…

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Negative / Null Result ReportOpen accessMedicine

Therapeutic Potential of Calcium Channel Blockers in Neuropsychiatric, Endocrine and Pain Disorders

Aarish Manzar, Aleksandar Sič, Crystal E. Banh et al. · 2025 · Cells

Calcium channel blockers (CCBs), originally developed for cardiovascular indications, have gained attention for their therapeutic potential in neuropsychiatric, endocrine, and pain-related disorders. In neuropsychiatry, nimodipine and isradipine, both L-type CCBs, show mood-stabilizing and neuroprotective effects, with possible benefits in depression, bipolar disorder, and schizophrenia. In endocrinology, verapamil, a non-dihydropyridine L-type blocker, has been associated with the preservation of pancreatic β-cell function and reduced insulin dependence in diabetes. CCBs may also aid in manag

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Negative / Null Result ReportOpen accessMedicine

Integrating Artificial Intelligence and PET Imaging for Drug Discovery: A Paradigm Shift in Immunotherapy

Jeremy McGale, Harrison J. Howell, Arnaud Beddok et al. · 2024 · Pharmaceuticals

The integration of artificial intelligence (AI) and positron emission tomography (PET) imaging has the potential to become a powerful tool in drug discovery. This review aims to provide an overview of the current state of research and highlight the potential for this alliance to advance pharmaceutical innovation by accelerating the development and deployment of novel therapeutics. We previously performed a scoping review of three databases (Embase, MEDLINE, and CENTRAL), identifying 87 studies published between 2018 and 2022 relevant to medical imaging (e.g., CT, PET, MRI), immunotherapy, arti

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Negative / Null Result ReportOpen accessMedicine

Safety and efficacy of valoctocogene roxaparvovec with prophylactic glucocorticoids: 1-year results from the phase 3b, single-arm, open-label GENEr8-3 study

Margareth C. Ozelo, Jane Mason, Amy L. Dunn et al. · 2025 · Journal of Thrombosis and Haemostasis

BACKGROUND: Valoctocogene roxaparvovec, an adeno-associated virus vector that transfers a human factor (F)VIII (FVIII) coding sequence to hepatocytes, provides bleeding protection for people with severe hemophilia A. OBJECTIVES: Determine…

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Negative / Null Result ReportOpen accessMedicine

Organ-on-a-Chip Models of the Female Reproductive System: Current Progress and Future Perspectives

Pan Min, Huike Chen, Kai Deng et al. · 2025 · Micromachines

The female reproductive system represents a highly complex regulatory network governing critical physiological functions, encompassing reproductive capacity and endocrine regulation that maintains female physiological homeostasis. The in vitro simulation system provides a novel tool for biomedical research and can be used as physiological and pathological models to study the female reproductive system. Recent advances in this technology have evolved from 2D and 3D printing to organ-on-a-chip (OOC) and microfluidic systems, which has emerged as a transformative platform for modeling the female

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Negative / Null Result ReportOpen accessMedicine

Physical activity for public health in the 21st century

Deborah Salvo, Inácio Crochemore-Silva, Andrea Wendt et al. · 2026 · Nature Medicine

With over 5 million attributed deaths per year, physical inactivity is a major global public health issue. Although the importance of physical activity is well recognized within the scope of obesity and cardiometabolic disease prevention…

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Negative / Null Result ReportOpen accessMedicine

The role of agentic artificial intelligence in healthcare: a scoping review

Bernardo G. Collaco, Syed Ali Haider, Srinivasagam Prabha et al. · 2026 · npj Digital Medicine

Agentic AI represents a promising evolution of artificial intelligence in healthcare, with systems capable of operating autonomously to achieve defined clinical goals. However, the literature lacks conceptual clarity in distinguishing AI…

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Negative / Null Result ReportOpen accessMedicine

Pre-existing cross-reactive immunity to highly pathogenic avian influenza 2.3.4.4b A(H5N1) virus in the United States

Zhu‐Nan Li, Feng Liu, Yu‐Jin Jung et al. · 2025 · Nature Communications

The unprecedented 2.3.4.4b. A(H5N1) outbreak in dairy cattle, poultry, and spillover to humans in the United States (US) poses a major public health threat. Population immunity is a critical component of influenza pandemic risk assessment. We assessed the pre-existing cross-reactive immunity to 2.3.4.4b A(H5N1) viruses and analyzed 1794 sera from 723 people (0.5-88 yrs) in multiple US geographic regions during 2021-2024. Pre-existing neutralizing and hemagglutinin (HA)-head-binding antibodies to A(H5N1) were low, but there were substantial cross-reactive binding antibodies to N1 neuraminidase

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Replication FailureOpen accessMedicine

Inhibition of FcRn with rozanolixizumab in adults with immune thrombocytopenia: Two randomised, double‐blind, placebo‐controlled phase 3 studies and their open‐label extension

Nichola Cooper, James B. Bussel, Maciej Kaźmierczak et al. · 2024 · British Journal of Haematology

Summary Primary immune thrombocytopenia (ITP) is an antiplatelet‐antibody‐mediated disorder with accelerated platelet clearance and decreased platelet production. Rozanolixizumab, a monoclonal IgG4 anti‐FcRn antibody, blocks IgG recycling and decreases IgG levels. We report efficacy and safety of rozanolixizumab in adults with persistent/chronic ITP in 24‐week phase 3 studies (TP0003; TP0006), and their 52‐week open‐label extension (OLE). Primary end‐point was durable clinically meaningful platelet response (DCMPR) of ≥50 × 10 9 /L for 8/12 weeks during Weeks 13–25 in the double‐blind studies.

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Negative / Null Result ReportOpen accessMedicine

Home-Based Prehabilitation for Older Surgical Patients With Frailty

Daniel I. McIsaac, Susan M. Lee, Dean Fergusson et al. · 2025 · JAMA Surgery

Importance: Explanatory trials suggest that prehabilitation has efficacy in improving surgical outcomes. The effectiveness of offering home-based prehabilitation across multiple centers and for older adults with frailty remains unknown. Objective: To evaluate the effectiveness of offering coach-supported, home-based prehabilitation to older surgical patients with frailty. Design, Setting, and Participants: This study is a pragmatic, parallel-arm, multicenter randomized clinical trial with embedded qualitative assessment. Clinicians and assessors were fully blinded; participants were partially

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Negative / Null Result ReportOpen accessMedicine

Long COVID trajectories in the prospectively followed RECOVER-Adult US cohort

Tanayott Thaweethai, Sarah E. Donohue, Jeffrey N. Martin et al. · 2025 · Nature Communications

Longitudinal trajectories of Long COVID remain ill-defined, yet are critically needed to advance clinical trials, patient care, and public health initiatives for millions of individuals with this condition. Long COVID trajectories were…

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Negative / Null Result ReportOpen accessMedicine

Anatomic Risk Factors for Initial and Secondary Noncontact Anterior Cruciate Ligament Injury: A Prospective Cohort Study in 880 Female Elite Handball and Soccer Players

Yusuke Kamatsuki, Marie Synnøve Qvale, Kathrin Steffen et al. · 2024 · The American Journal of Sports Medicine

Background: Anterior cruciate ligament (ACL) injury is one of the most severe injuries for athletes. It is important to identify risk factors because a better understanding of injury causation can help inform athletes about risk and increase their understanding of and motivation for injury prevention. Purpose: To investigate the relationship between anatomic factors and risk for future noncontact ACL injuries. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 870, excluding 9 players with a new contact ACL injury and a player with a new noncontact ACL injury just before the

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Negative / Null Result ReportOpen accessMedicine

The intragenic epistatic association of ADD3 with biliary atresia in Southern Han Chinese population

Zhe Wang, Xiaoli Xie, Jinglu Zhao et al. · 2018 · Bioscience Reports

Biliary atresia (BA) is a multifactorial pathogenic disease with possible genetic components. As a member of membrane skeletal proteins in the liver and bile ducts, a haplotype composed by five single nucleotide polymorphisms (SNPs) on adducin 3 (ADD3) has been identified as associated with BA. However, limited study was designed to further elaborate the mutual relationship amongst those replicated SNPs to disease. We selected three susceptibility SNPs in ADD3 and conducted a replication study using 510 BA cases and 1473 controls to evaluate the individual function of the SNPs and further stra

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Negative / Null Result ReportOpen accessMedicine

Update on Clinical Trials for Nonalcoholic Steatohepatitis.

Rohit Nathani, Meena B. Bansal · 2023 · PubMed

Tremendous effort has been put forth over the past 2 decades in understanding the pathophysiology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH). Although multiple potential targets for drug development…

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Negative / Null Result ReportOpen accessMedicine

Inhibition of Toll-like receptor 4 and Interleukin-1 receptor prevent SARS-CoV-2 mediated kidney injury

Daigo Nakazawa, Yohei Takeda, Masatoshi Kanda et al. · 2023 · Cell Death Discovery

Acute kidney injury (AKI) is a common and severe complication of the coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly affects the glomerular and tubular epithelial cells to induce AKI; however, its pathophysiology remains unclear. Here, we explored the underlying mechanisms and therapeutic targets of renal involvement in COVID-19. We developed an in vitro human kidney cellular model, including immortalized tubular epithelial and endothelial cell lines, demonstrating that SARS-CoV-2 directly triggers cell death. To identify the molecular

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Negative / Null Result ReportOpen accessMedicine

Temporal validation of machine learning models for pre-eclampsia prediction using routinely collected maternal characteristics: A validation study

Sofonyas Abebaw Tiruneh, Daniel L. Rolnik, Helena Teede et al. · 2025 · Computers in Biology and Medicine

BACKGROUND: Pre-eclampsia (PE) contributes to more than one-fourth of all maternal deaths and half a million newborn deaths worldwide every year. Early screening and interventions can reduce PE incidence and related complications. We aim to 1) temporally validate three existing models (two machine learning (ML) and one logistic regression) developed in the same region and 2) compare the performances of the validated ML models with the logistic regression model in PE prediction. This work addresses a gap in the literature by undertaking a comprehensive evaluation of existing risk prediction mod

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Negative / Null Result ReportOpen accessMedicine

Beneath the surface: Amino acid variation underlying two decades of dengue virus antigenic dynamics in Bangkok, Thailand

Angkana T. Huang, Henrik Salje, Ana Coello Escoto et al. · 2022 · PLoS Pathogens

Neutralizing antibodies are important correlates of protection against dengue. Yet, determinants of variation in neutralization across strains within the four dengue virus serotypes (DENV1-4) is imperfectly understood. Studies focus on structural DENV proteins, especially the envelope (E), the primary target of anti-DENV antibodies. Although changes in immune recognition (antigenicity) are often attributed to variation in epitope residues, viral processes influencing conformation and epitope accessibility also affect neutralizability, suggesting possible modulating roles of nonstructural prote

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Negative / Null Result ReportOpen accessMedicine

Circulating PD-L1 levels change during bevacizumab-based treatment in recurrent glioma

Maximilian J. Mair, Aysegül Ilhan‐Mutlu, Sahra Pajenda et al. · 2021 · Cancer Immunology Immunotherapy

PURPOSE: In primary brain tumors, the efficacy of immune-modulating therapies is still under investigation as inflammatory responses are restricted by tight immunoregulatory mechanisms in the central nervous system. Here, we measured soluble PD-L1 (sPD-L1) in the plasma of patients with recurrent glioblastoma (GBM) and recurrent WHO grade II-III glioma treated with bevacizumab-based salvage therapy. METHODS: Thirty patients with recurrent GBM and 10 patients with recurrent WHO grade II-III glioma were treated with bevacizumab-based salvage therapy at the Medical University of Vienna. Prior to

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Negative / Null Result ReportOpen accessMedicine

Plasma proteomics for prediction of subclinical coronary artery calcifications in primary prevention

Patrick Royer, Elias Björnson, Martin Adiels et al. · 2024 · American Heart Journal

BACKGROUND AND AIMS: Recent developments in high-throughput proteomic technologies enable the discovery of novel biomarkers of coronary atherosclerosis. The aims of this study were to test if plasma protein subsets could detect coronary artery calcifications (CAC) in asymptomatic individuals and if they add predictive value beyond traditional risk factors. METHODS: Using proximity extension assays, 1,342 plasma proteins were measured in 1,827 individuals from the Impaired Glucose Tolerance and Microbiota (IGTM) study and 883 individuals from the Swedish Cardiopulmonary BioImage Study (SCAPIS)

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Negative / Null Result ReportMedicine

Evaluation of Pelvic Circular Compression Devices in Severely Injured Trauma Patients with Pelvic Fractures

Josephine Berger-Groch, Johannes M. Rueger, Patrick Czorlich et al. · 2021 · Prehospital Emergency Care

Background: The role of pelvic circumferential compression devices (PCCD) is to temporarily stabilize the pelvic ring, reduce its volume and to tamponade bleeding. The purpose of this study was to evaluate the effect of PCCDs on mortality…

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