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11,309 real negative results, null findings, and replication failures in Medicine · Negative / Null Result Report. 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

Why Is Clozapine Uniquely Effective in Treatment-Resistant Schizophrenia? A Review and Proposal

Robin Murray, Alice Egerton, Yueming Gao et al. · 2025 · Biological Psychiatry

Much is known about the use, benefits, and side-effects, of clozapine in treatment resistant schizophrenia (TRS). However, why clozapine is more effective than other antipsychotics in TRS remains unclear. This paper addresses this question. TRS patients show glutamate abnormalities, and clozapine has widespread effects on glutamate. However, these actions have not been proven different to those of other antipsychotics. Immune dysfunction is also reported in TRS, and clozapine has anti-inflammatory actions, but these have not been correlated with clinical improvement. Currently, there is much i

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Negative / Null Result ReportOpen accessMedicine

Integration of Artificial Intelligence-Enhanced Capsule Endoscopy in Clinical Practice: A Review of Market-Available Tools for Clinical Practice

A. Giordano, Cristina Romero-Mascarell, Begoña González-Suárez et al. · 2025 · Digestive Diseases and Sciences

The integration of artificial intelligence (AI) into capsule endoscopy is transforming gastrointestinal diagnostics by enhancing lesion detection and optimizing reading efficiency. This review focuses on the clinical applications of…

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Negative / Null Result ReportOpen accessMedicine

Natural history of the revised ALS functional rating scale and its association with survival: the PRECISION-ALS Extant Study

Ruben P. A. van Eijk, Daphne N. Weemering, Sarah Opie-Martin et al. · 2025 · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

Objective To characterize the natural history of the revised ALS functional rating scale (ALSFRS-R) over a 24-month period following initial assessment, and to assess its associations with survival.Methods Longitudinal ALSFRS-R…

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Negative / Null Result ReportOpen accessMedicine

Learning with Generative AI: An Empirical Study of Students in Higher Education

Golan Carmi · 2025 · Education Sciences

Generative AI technologies are rapidly permeating higher education as innovative tools that support teaching and learning processes. This study investigates the integration of GenAI tools into academic learning and examines their influence on students’ learning effectiveness, attitudes, and satisfaction. A quantitative survey was administered to 485 college students. The findings indicate that students’ attitudes, satisfaction, and accumulated experience with GenAI constitute the most influential factors in promoting effective learning. Perceived advantages and disadvantages also play a substa

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Negative / Null Result ReportOpen accessMedicine

Integration of plasma eMTBR-tau243 and p-tau217 in the diagnosis and stratification of Alzheimer's disease: a prospective cohort study

Niklas Mattsson-Carlgren, Sebastian Palmqvist, Kanta Horie et al. · 2026 · The Lancet Neurology

BACKGROUND: Alzheimer's disease pathology can be accurately identified with blood biomarkers (core 1 biomarkers), including plasma p-tau217 tests. Biomarkers that change longitudinally after diagnosis (core 2 biomarkers) can increase confidence that Alzheimer's disease pathology is contributing to cognitive symptoms. Plasma eMTBR-tau243 reflects tau tangle pathology and is a promising core 2 biomarker. We aimed to examine whether, among patients positive for plasma p-tau217, plasma eMTBR-tau243 improves classification of established Alzheimer's disease and predicts cognitive decline and tau ta

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Negative / Null Result ReportOpen accessMedicine

Tracing the origin of myofibroblasts in kidney fibrosis

Shun He, Tianchang Xia, Zhihou Guo et al. · 2025 · Nature Communications

Kidney fibrosis is a key pathological feature of chronic kidney disease (CKD), characterized by the activation and accumulation of αSMA-positive myofibroblasts. The cellular origin of myofibroblasts in kidney fibrosis has been a subject of…

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Negative / Null Result ReportOpen accessMedicine

Resveratrol in food systems: challenges, innovations, and health potential

Jenny Bouchard, Nicola Gasparre, Thomas Netticadan et al. · 2025 · Journal of Functional Foods

The integration of resveratrol, a naturally occurring, health promoting polyphenolic stilbene, into food systems poses a challenge due to its low water solubility, chemical instability, poor bioavailability, and bitter taste. To address…

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Negative / Null Result ReportOpen accessMedicine

Tissue-resident macrophage survival depends on mitochondrial function regulated by SerpinB2 in chronic inflammation

Sathish Babu Vasamsetti, Samreen Sadaf, Mohammad A. Uddin et al. · 2026 · Nature Communications

How cellular metabolism facilitates tissue-resident macrophage maintenance remains elusive. Here we show that visceral adipose tissue (VAT)-resident macrophages, unlike monocyte-derived macrophages, are enriched with mitochondrial-specific antioxidant enzymes restraining inflammation and promoting VAT homeostasis and insulin sensitivity. Additionally, VAT resident macrophages express high levels of plasminogen activator inhibitor type 2, encoded by SerpinB2, which is involved in the blood coagulation cascade. SerpinB2 promotes adipose resident macrophage survival by regulating mitochondrial ox

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Negative / Null Result ReportOpen accessMedicine

Osteoarthritis: molecular pathogenesis and potential therapeutic options

Yi Zhang, Yanqi Han, Ying Sun et al. · 2026 · Signal Transduction and Targeted Therapy

Osteoarthritis (OA) is a debilitating joint disorder that causes chronic pain, inflammation, and detrimental bone alterations. Despite significant advances in understanding OA pathogenesis, current therapeutic strategies remain inadequate in halting disease progression or providing effective pain relief, highlighting unmet clinical needs. Recent insights into OA nociceptive pathways, inflammatory mediators, and organelle dysfunction have revealed promising therapeutic targets. Specifically, OA progression is driven by mitochondrial dysfunction (marked by accumulated damaged mitochondria with e

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Negative / Null Result ReportOpen accessMedicine

Mitochondrial Health Through Nicotinamide Riboside and Berberine: Shared Pathways and Therapeutic Potential

F Visalli, Matteo Capobianco, F. Cappellani et al. · 2026 · International Journal of Molecular Sciences

Mitochondrial dysfunction represents a central hallmark of aging and a broad spectrum of chronic diseases, ranging from metabolic to neurodegenerative and ocular disorders. Nicotinamide riboside (NR), a vitamin B3 derivative and efficient precursor of NAD+ (nicotinamide adenine dinucleotide), and berberine (BBR), an isoquinoline alkaloid widely investigated in metabolic regulation, have independently emerged as promising mitochondrial modulators. NR enhances cellular NAD+ pools, thereby activating sirtuin-dependent pathways, stimulating PGC-1α–mediated mitochondrial biogenesis, and triggering

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Negative / Null Result ReportOpen accessMedicine

Performance and challenges of malaria rapid diagnostic tests in endemic regions of Africa

Fiyinfoluwa Demilade Ojeniyi, Adeola Oluwakemi Ayoola, Olajumoke Ibitoye et al. · 2025 · Scientific Reports

Rapid diagnostic tests (RDTs) have revolutionized malaria diagnosis, playing a crucial role in improving timely treatment and supporting surveillance efforts, especially in resource-limited settings. However, the performance of RDTs can…

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Negative / Null Result ReportOpen accessMedicine

Title Oxidative Stress in Age-Related Macular Degeneration: From Molecular Mechanisms to Emerging Therapeutic Targets

Tatsuya Mimura, Hidetaka Noma · 2025 · Antioxidants

Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in the elderly, and oxidative stress, primarily mediated by reactive oxygen species (ROS), is widely recognized as a central driver of its onset and progression. The retina is highly susceptible to oxidative damage due to its elevated oxygen consumption, abundant polyunsaturated fatty acids, and continuous exposure to light. Recent studies have elucidated molecular mechanisms in which mitochondrial dysfunction, disruption of redox homeostasis, inflammation, and complement activation interact to promote

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Negative / Null Result ReportOpen accessMedicine

Advances in the intrinsic signaling pathway interactions and clinical translation of HR+/HER2+ breast cancer

Xinyu Li, Tao Huang · 2025 · Breast Cancer

Hormone receptor-positive (HR +) and HER2-positive (HER2+) breast cancers represent a biologically unique subset of breast malignancies characterized by the co-expression of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2). These cancers exhibit distinct molecular features, often leading to aggressive growth and higher recurrence rates. HR+/HER2+ breast cancer cells can utilize estrogen and HER2-driven signaling pathways to promote proliferation, survival, and metastatic potential, presenting unique challenges and opportunities for treat

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Negative / Null Result ReportOpen accessMedicine

Antibody drug conjugate targets are highly differentially expressed across the major types of ovarian cancer

Joanna M Porter, Cici Jin, Michael Churchman et al. · 2025 · European Journal of Cancer

BACKGROUND: Antibody-drug conjugates (ADCs) are emerging anti-cancer agents. The folate receptor alpha (FOLRα)-directed ADC mirvetuximab soravtansine recently demonstrated clinical activity in platinum-resistant ovarian cancer, with other ADCs currently in development. The relative expression of FOLRα and other ADC targets is largely unknown across ovarian cancer histotypes. METHODS: Expression levels of the ADC targets FOLRα, TROP2 and B7-H4 were assessed by immunohistochemistry in patient cohorts using tumour tissue microarrays of the major ovarian cancer histotypes: high grade serous (HGSOC

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Negative / Null Result ReportOpen accessMedicine

Distinct brain alterations and neurodegenerative processes in cognitive impairment associated with post-acute sequelae of COVID-19

Dayoung Seo, Yangsean Choi, Eunseon Jeong et al. · 2025 · Nature Communications

Although brain alterations have been reported in post-acute sequelae of SARS-CoV-2 (PASC), their prevalence and relationship to neurodegeneration remain unclear. We analyzed blood proteins and brain MRI from individuals approximately one…

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Negative / Null Result ReportOpen accessMedicine

Evaluating the role of CHG index in predicting stroke risk among adults with varying glucose regulation

Qun Xiao, WeiCheng Huang, Yuheng Zhuang et al. · 2025 · Aging Clinical and Experimental Research

BACKGROUND: Stroke is a significant public health issue, with its risk influenced by various metabolic factors. The Cholesterol, High-Density Lipoprotein, Glucose (CHG) index has been identified as a valid stroke predictor. However, the…

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Negative / Null Result ReportOpen accessMedicine

Maximizing the Utility of Alzheimer's Disease Trial Data: Sharing of Baseline A4 and LEARN Data

Gustavo Jimenez‐Maggiora, Arndt‐Peter Schulz, Michael Donohue et al. · 2024 · The Journal of Prevention of Alzheimer s Disease

BACKGROUND: The Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies were conducted between 2014 and 2023, with enrollment completed in 2017 and final study results reported in 2023. The study screening process involved the collection of initial clinical, cognitive, neuroimaging, and genetic measures to determine eligibility. Once randomized, enrolled participants were assessed every four weeks over a 4.5-year follow-up period during which longitudinal clinical, cognitive, and neuroimaging measures wer

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Negative / Null Result ReportOpen accessMedicine

The Functional Role of Polyphenols Across the Human Lifespan

Bekir Enes Koca, Sümeyye Sarıtaş, Mikhaël Bechelany et al. · 2025 · International Journal of Molecular Sciences

Polyphenols are bioactive molecules that occur naturally in plants and exhibit a diverse array of properties, including antioxidant, anti-inflammatory, and anti-obesity effects, all of which have been supported by numerous studies. They are categorized into four main groups: flavonoids, phenolic acids, stilbenes, and lignans. Polyphenols demonstrate a wide range of health-promoting effects throughout human life, from the womb to old age. They can exert these effects by modulating signaling pathways, regulating gut microbiota, influencing gene expression, and regulating epigenetic pathways. Thi

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Negative / Null Result ReportOpen accessMedicine

Anti-inflammatory agents for the management of COPD - Quo Vadis?

Agamemnon Bakakos, Zoi Sotiropoulou, Nektarios Anagnostopoulos et al. · 2025 · Respiratory Medicine

Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality around the globe. Its main characteristics are persistent respiratory symptoms and progressive airflow limitation, both of which are driven by chronic inflammation. Despite the use of maximum bronchodilation and in selected patients inhaled corticosteroids (ICS), current therapies neither halt disease progression nor prevent exacerbations and loss of lung function. Recent research has focused on developing novel anti-inflammatory agents targeting specific pathways implicated in COPD pathogenesis, ai

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Negative / Null Result ReportOpen accessMedicine

Oxygen level alters energy metabolism in bovine preimplantation embryos

Nina Boskovic, Marilin Ivask, Gamze Yazgeldi Gunaydin et al. · 2025 · Scientific Reports

Abstract Mammalian preimplantation embryo development is a complex sequence of events. This period of development is sensitive to oxygen (O 2 ) levels that can affect various cellular processes. We compared the influence of O 2 tension by culturing embryos either in normoxic (20% O 2 ) or physiological hypoxic (6% O 2 ) conditions, or sequential low O 2 concentration starting with 6% O 2 until 16-cell stage and then switching to ultrahypoxic conditions (2% O 2 ). Due to ethical concerns, we used bovine as an animal model with a good similarity of embryogenesis to human. We found that the cleav

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Negative / Null Result ReportOpen accessMedicine

Cetuximab Reduces the Accumulation of Radiolabeled Bevacizumab in Cancer Xenografts without Decreasing VEGF Expression

Sandra Heskamp, Otto C. Boerman, Janneke D.M. Molkenboer‐Kuenen et al. · 2014 · Molecular Pharmaceutics

Bevacizumab and cetuximab are approved for the treatment of cancer. However, in advanced colorectal cancer, addition of cetuximab to chemotherapy with bevacizumab did not improve survival. The reason for the lack of activity remains…

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Negative / Null Result ReportOpen accessMedicine

Non-invasive temporal interference stimulation of the hippocampus suppresses epileptic biomarkers in patients with Epilepsy: biophysical differences between kilohertz and amplitude modulated stimulation

Florian Missey, Emma Acerbo, Adam S. Dickey et al. · 2025 · Brain stimulation

INTRODUCTION: Medication-refractory focal epilepsy creates a significant clinical challenge, with approximately 30 % of patients deemed ineligible for surgery due to involvement of eloquent cortical regions within the epileptogenic network. For these patients, electrical neuromodulation represents a promising alternative therapy. We investigated the potential of non-invasive temporal interference (TI) electrical stimulation in reducing epileptic biomarkers in patients with mesiotemporal epilepsy (MTLE) MATERIAL AND METHOD: Thirteen patients implanted with stereoelectroencephalography (sEEG) de

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Negative / Null Result ReportOpen accessMedicine

SGLT-2 Inhibitors and GLP-1 Receptor Agonists as Combination Therapy in Type 2 Diabetes

Aris Liakos, Thomas Karagiannis, Ioannis Avgerinos et al. · 2026 · Current Diabetes Reports

PURPOSE OF REVIEW: The pharmacologic management of type 2 diabetes prioritises sodium-glucose cotransporter 2 (SGLT-2) inhibitors or glucagon-like peptide 1 (GLP-1) receptor agonists for their demonstrated cardiovascular benefits in individuals with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors, chronic kidney disease, and heart failure. However, while current guidelines recommend these drug classes alone, combination therapy is not explicitly advocated. Herein we summarise the rationale and available evidence in support for combination therapy. RECENT FINDINGS

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Negative / Null Result ReportOpen accessMedicine

Improving medication adherence in type 2 diabetes: strategies for better clinical and economic outcomes

Patrick Highton, Mark P. Funnell, Pankaj Gupta et al. · 2025 · Diabetologia

Abstract Medication adherence is critical for optimal glycaemic management and the prevention of complications in type 2 diabetes mellitus. Despite its importance, non-adherence remains a prevalent issue, with global estimates suggesting that approximately 38% of people with type 2 diabetes do not take their medications as prescribed, although estimates vary widely due to a range of patient-related, socioeconomic, condition-related (e.g. chronicity, severity of comorbidities) and healthcare system factors. This review synthesises the current evidence on the prevalence of non-adherence in type

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Negative / Null Result ReportOpen accessMedicine

Silybin A from Silybum marianum reprograms lipid metabolism to induce a cell fate-dependent class switch from triglycerides to phospholipids

Solveigh C. Koeberle, Maria Thürmer, Fengting Su et al. · 2025 · Theranostics

: Our study deciphers the structural features of silybin contributing to hepatic lipid remodeling and suggests that silymarin/silybin protects the liver in individuals with mild metabolic dysregulation, involving a lipid class switch from triglycerides to phospholipids, whereas it may be less effective in disease states associated with severe metabolic dysregulation.

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