e-ISSN: Pending
Failure-mode index

Search what already failed

A searchable index of real negative results, null findings, and replication failures from the published literature — so you can learn what didn't work before repeating it.

WASTE indexes published research — it does not host or republish full papers. Each entry is a metadata record (title, authors, DOI) compiled from open scholarly databases, with the abstract shown in full only where the paper is openly licensed (e.g. Creative Commons); otherwise a short excerpt is shown for reference under fair use. WASTE classifies each work by failure type; classifications are automated and approximate.

21742 results · page 677 of 725

Negative / Null Result ReportOpen accessAgriculture (General)

Estimation of aboveground biomass of Alfalfa using field robotics

Jasanmol Singh, Ali Bulent Koc, Matias Jose Aguerre et al. · 2024 · Smart Agricultural Technology

Alfalfa is a high-yielding forage crop that is widely grown in the United States for grazing, hay and silage making. A proper maintenance of these grasslands is necessary to ensure optimum productivity and profits. The pre-harvest estimation of biomass yield helps in quantifying the profits and optimizing the forage allocation in advance. Most traditional methods of forage estimation are relatively laborious and time-consuming. Recent developments in contact and remote sensing technologies opened numerous paths for performing aboveground biomass estimation tasks with flexibility and easiness.

View details →DOI: 10.1016/j.atech.2024.100597
Negative / Null Result ReportOpen accessTherapeutics. Pharmacology

Ineffective behavioral rescue despite partial brain Dp427 restoration by AAV9-U7-mediated exon 51 skipping in mdx52 mice

Ophélie Vacca, Amel Saoudi, Mathilde Doisy et al. · 2025 · Molecular Therapy: Nucleic Acids

The mdx52 mouse model exhibits a common mutation profile associated with brain involvement in Duchenne muscular dystrophy (DMD), characterized by heightened anxiety, fearfulness, and impaired associative fear learning. Deletion of exon 52 disrupts the expression of two dystrophins found in the brain (Dp427 and Dp140) and is eligible for therapeutic exon-skipping strategies. We previously demonstrated that a single intracerebroventricular administration of an antisense oligonucleotide (ASO) targeting exon 51 of the Dmd gene could restore 5%–15% of Dp427 expression. This treatment reduced anxiet

View details →DOI: 10.1016/j.omtn.2025.102779
Negative / Null Result ReportOpen accessOrthopedic surgery

In vivo cartilage tissue engineering

B. Gurer, S. Cabuk, O. Karakus et al. · 2018 · Journal of Orthopaedic Surgery and Research

Abstract Background Biologic treatment options for cartilage injuries require chondrocyte expansion using cell culture. Clinical application is accomplished in two surgical sessions and is expensive. If isolation of chondrocytes and stimulus for proliferation and extracellular matrix synthesis can be achieved in vivo, the treatment can be performed in one session and the cost can be reduced. Methods A 2.5-cm diameter full-thickness chondral defect was created in the knees of five groups of sheep. In one group, some of the chondral tissues obtained from the creation of the defect were diced int

View details →DOI: 10.1186/s13018-018-0823-0
Negative / Null Result ReportOpen accessMedicine

Post-thoracotomy paraplegia after oxidized cellulose spinal compression

Da Jun Than, Vinodh Vayara Perumall, Syamim Johan et al. · 2023 · Einstein (São Paulo)

ABSTRACT Post-thoracotomy paraplegia after non-aortic surgery is an extremely uncommon complication. A 56-year-old woman presented with a 1-year history of progressive shortness of breath. Computed tomography revealed a locally advanced posterior mediastinal mass involving the ribs and the left neural foramina. Tumor excision with a left pneumonectomy was performed. Post-resection, bleeding was noted in the vicinity of the T4-T5 vertebral body, and the bleeding point was packed with oxidized cellulose gauze (Surgicel®). Postoperatively, the patient complained of bilateral leg numbness extendin

View details →DOI: 10.31744/einstein_journal/2023rc0078
Negative / Null Result ReportOpen accessPublic aspects of medicine

Wastewater as an early indicator for short-term forecasting COVID-19 hospitalization in Germany

Jonas Radermacher, Steffen Thiel, Aimo Kannt et al. · 2025 · BMC Public Health

Abstract Background The COVID-19 pandemic has profoundly affected daily life and posed significant challenges for politics, the economy, and the education system. To better prepare for such situations and implement effective measures, it is crucial to accurately assess, monitor, and forecast the progression of a pandemic. This study examines the potential of integrating wastewater surveillance data to enhance an autoregressive COVID-19 forecasting model for Germany and its federal states. Methods First, we explore the cross-correlations between SARS-CoV-2 viral RNA load measured in wastewater

View details →DOI: 10.1186/s12889-025-24149-2
Negative / Null Result ReportOpen accessMedicine

Social-pair judgment bias testing in slow-growing broiler chickens raised in low- or high-complexity environments

M. I. Lourenço-Silva, A. Ulans, A. M. Campbell et al. · 2023 · Scientific Reports

Abstract Impacts of environmental complexity on affective states in slow-growing broiler chickens (Gallus gallus domesticus) are unknown. Chickens’ performance in judgment bias tests (JBT) can be limited as they are tested individually, causing fear and anxiety. The objectives were to apply a social-pair JBT to assess the effect of environmental complexity on slow-growing broiler chickens` affective states, and assess the impact of fearfulness, anxiety, and chronic stress on JBT performance. Six-hundred Hubbard Redbro broilers were housed in six low-complexity (similar to commercial) or six hi

View details →DOI: 10.1038/s41598-023-36275-1
Negative / Null Result ReportOpen accessMedicine (General)

Gender Differences in the Association Between Serum Uric Acid and Arteriosclerotic Cardiovascular Risk Among Chinese Type 2 Diabetes Mellitus Patients

Yang H, Gao J, Li S et al. · 2021 · International Journal of General Medicine

Hua Yang,1,* Jian Gao,2,* Shuyu Li,1 Huiling Xia,1 Zhangyan Chen,1 Shanzhu Zhu,1 Zhigang Pan1 1Department of General Practice, Zhongshan Hospital of Fudan University, Shanghai, 200030, People’s Republic of China; 2Department of Nutrition, Zhongshan Hospital of Fudan University, Center of Clinical Epidemiology and Evidence-Based Medicine, Fudan University, Shanghai, 200030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shanzhu Zhu; Zhigang PanDepartment of General Practice, Zhongshan Hospital of Fudan University, No. 180, Road Fenglin, Shan

Negative / Null Result ReportOpen accessPediatrics

Nonlinear association between neutrophil-to-lymphocyte ratio and asthma in children and adolescents in the United States: a cross-sectional study

Chuhan Cheng, Liyan Zhang · 2025 · Clinical and Experimental Pediatrics

Background The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation associated with various diseases including respiratory conditions. However, the relationship between NLR and asthma in the pediatric population remains underexplored. Purpose This study aimed to explore the association between NLR and asthma in children and adolescents and assess its potential role as a predictive biomarker for pediatric asthma. Methods We retrospectively analyzed the medical records of 12,974 children and adolescents from the National Health and Nutrition Examination Survey in 2011–2020.

View details →DOI: 10.3345/cep.2024.01844
Negative / Null Result ReportOpen accessMedicine

Relation between vitamin D serum levels with migraine

Mottaghi T, Askari Gh, Khorvash F et al. · 2015 · مجله دانشگاه علوم پزشکی گرگان

Background and Objective: Migraine is common worldwide. In recent years, vitamin D deficiency has been shown as a global health issue. This study was done to determine the relationship between serum levels of vitamin D with migraine. Methods: This descriptive - analytical study was carried out on 76 patients (21 males, 55 females) with migraine aged 10-61 years olds. Serum vitamin D level of each patient was measured. Adjustments were done for age, sex, waist circumference, body mass index (BMI), number of chronic diseases, and education level. The multiple linear regressions were done to dete

Negative / Null Result ReportOpen accessMedicine

Study on Association Between Lipid Profile Values and Psychiatric Disorders

SHINY JOHN, KAVITARATI DHARWADKAR, MANJUNATH V MOTAGI · 2014 · Journal of Clinical and Diagnostic Research

Background: Cholesterol is especially abundant in nervous system, where it plays important role in different aspects of cellular structure (e.g. fluidity of cell membranes) and function (e.g. membrane). Several studies showed that there may be a link between depression and low cholesterol because of altered central serotonergic functions. On the other hand, some studies also showed either no such association or yielded inconsistent results. However, many studies have related low cholesterol with different psychiatric disorders. Hence, we intend to see the possible link between the two. Aim: To

View details →DOI: 10.7860/jcdr/2014/10383.5301
Negative / Null Result ReportOpen accessMedicine

The burden of care and the understanding of disease in Parkinson's disease.

Geum-Bong Lee, Hyunhee Woo, Su-Yoon Lee et al. · 2019 · PLoS ONE

Background and objective Education of disease plays an important role in management of Parkinson's disease (PD). However, little is known about the link between the understanding of disease and the burden of care. This study was carried out to find the correlation between the burden of care and the understanding of disease in caregivers for PD patients. Methods Non-demented patients with PD and their caregivers participated in structured interviews. Understanding of patients and caregivers was evaluated through newly-devised questions. The caregiver burden inventory was used to assess the burd

View details →DOI: 10.1371/journal.pone.0217581
Negative / Null Result ReportOpen accessBiotechnology

Association of SNP Rs34678647 with breast cancer risk in the Vietnamese population: An initial study

Nga Thi Nguyen, Thanh Thi Ngoc Nguyen, Hue Thi Nguyen · 2025 · Ho Chi Minh City Open University Journal of Science - Engineering and Technology

Breast cancer remains a leading cause of mortality among women worldwide. In Vietnam, the rising incidence underscores the urgent need for early diagnostic markers. Genetic factors, particularly Single Nucleotide Polymorphisms (SNPs), play a critical role in breast cancer susceptibility. The SNP rs34678647, located downstream of the miR-221/222 cluster targeting Estrogen Receptor alpha (ERα), is hypothesized to influence breast cancer risk by modulating cancer-related pathways. This study investigates the association between rs34678647 and breast cancer risk in the Vietnamese population. A tot

View details →DOI: 10.46223/hcmcoujs.tech.en.15.2.4248.2025
Negative / Null Result ReportOpen accessMedicine

Clinical Factors and Disease Course Related to Diagnostic Delay in Korean Crohn's Disease Patients: Results from the CONNECT Study.

Chang Mo Moon, Sung-Ae Jung, Seong-Eun Kim et al. · 2015 · PLoS ONE

Diagnostic delay frequently occurs in Crohn's disease (CD) patients because of diagnostic limitations. However, diagnostic delay and its related factors remain poorly defined. Therefore, we aimed to identify the predictors associated with diagnostic delay and to evaluate the impact of diagnostic delay on clinical course in a Korean CD patient cohort. We performed a multicenter retrospective analysis of 1,047 CD patients registered in the Crohn's Disease Clinical Network and Cohort study in Korea. The mean interval of diagnostic delay was 16.0 ± 33.1 months. Multivariate analysis showed that ol

View details →DOI: 10.1371/journal.pone.0144390
Negative / Null Result ReportOpen accessMedicine (General)

Misconceptions and negative attitudes towards the metabolic effects of Ramadan fasting, resulting in fasting avoidance

Zhaleh Shadman, Nooshin Poorsoltan, Mahdieh Akhoundan et al. · 2014 · Journal of Fasting and Health

The aim of this study was to assess public knowledge about the effects of Ramadan fasting on various aspects of health and its association with fasting decision-making. This cross-sectional study was conducted on 600 subjects. The association between fasting and participants’ knowledge and attitudes toward Ramadan fasting, anthropometric measurements, physical activity, depression, anxiety, stress, dietary intake, and prior history of diseases was evaluated. The results indicated an adverse correlation between negative attitudes towards the effects of Ramadan fasting and adherence to fasting (

View details →DOI: 10.22038/jfh.2014.3682
Negative / Null Result ReportOpen accessMedicine

The Relationships of Dehydroepiandrosterone Sulfate, Erectile Function and General Psychological Health

Kanglai Li, BD, Shangyan Liang, MD, Yuyan Shi, BD et al. · 2021 · Sexual Medicine

Introduction: Dehydroepiandrosterone sulfate (DHEAS) has been reported to be associated with sexual function and general psychological health respectively, however, no one has ever examined their mutual relationships in a single study. Aim: The aim of the present study was to find out whether DHEAS, general psychological health, and erectile function were all associated with each other. Methods: A cross-sectional study was conducted on 34 patients with erectile dysfunction (ED) and 32 healthy controls (HC). The levels of serum DHEAS were assessed by chemiluminescence method. Erectile function

View details →DOI: 10.1016/j.esxm.2021.100386
Negative / Null Result ReportOpen accessMedicine

Relationship between manual dexterity and left–right asymmetry of anatomical and functional properties of corticofugal tracts revealed by T2-weighted brain images

Noriyuki Oka, Masaharu Sakoh, Misato Hirayama et al. · 2023 · Scientific Reports

Abstract The corticofugal tracts (CFT) are key agents of upper limb motor function. Although the tracts form high-intensity regions relative to surrounding tissue in T2-weighted magnetic resonance images (T2WI), the precise relations of signal intensities of the left and right CFT regions to hand function are unknown. Here, we tested the hypothesis that the different signal intensities between the left and right CFT signify clinically important differences of hand motor function. Eleven right-handed and eleven left-handed healthy volunteers participated in the study. Based on horizontal T2WI e

View details →DOI: 10.1038/s41598-023-29557-1
Negative / Null Result ReportOpen accessMedicine (General)

Nonlinear association between hematocrit and 3-month outcome after acute ischemic stroke: identification of threshold effects in males

Xiaomin Liang, Qian Wang, Zemao Xing et al. · 2026 · Frontiers in Medicine

ObjectiveAcute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. Hematocrit (HCT), the proportion of blood volume occupied by red blood cells, has been associated with outcome in AIS patients, but the relationship remains controversial. This study aimed to investigate the association between HCT levels and 3-month adverse outcome in South Korean patients with AIS, with a focus on potential sex differences.MethodsThis secondary analysis utilized data from an existing South Korean prospective cohort study involving 1,896 AIS patients. HCT was assessed both as a cont

View details →DOI: 10.3389/fmed.2026.1721251
Negative / Null Result ReportOpen accessArctic medicine. Tropical medicine

Seroprevalence for hepatitis E virus (HEV) infection among volunteer blood donors of the Regional Blood Bank of Londrina, State of Paraná , Brazil Soroprevalência da infecção pelo virus da hepatite E (VHE) em candidatos a doadores de sangue voluntários do Hemocentro Regional de Londrina, Londrina, Estado do Paraná, Brasil

André Luiz Bortoliero, Ana Maria Bonametti, Helena Kaminami Morimoto et al. · 2006 · Revista do Instituto de Medicina Tropical de São Paulo

A cross-sectional study was carried out among 996 volunteer blood donors enrolled from May 1999 to December 1999 to determine the seroprevalence of hepatitis E virus (HEV) infection among volunteer blood donors of the Regional Blood Bank of Londrina, State of Paraná, Brazil, and to evaluate whether the rate of seroprevalence of IgG anti-HEV antibodies is associated with sociodemographic variables and with seropositivity for hepatitis A virus (HAV) infection. All participants answered the questionnaire regarding the sociodemographic characterisitcs. Serum samples were tested for IgG antibodies

View details →DOI: 10.1590/s0036-46652006000200006
Negative / Null Result ReportOpen accessMedicine (General)

Relationship Between Helicobacter Pylori Infection and Chronic Obstructive Pulmonary Disease

Mohammad-Ali Seif-Rabiei, Mehrdad Hajilooi, Uldoz Roustaei et al. · 2011 · Acta Medica Iranica

There is some evidence indicating the role of Helicobacter pylori infection in pathogenesis of extragastrointestinal diseases including skin, vascular, and autoimmune disorders, as well as some respiratory diseases. The aim of this study was to investigate the association between H. pylori and chronic obstructive pulmonary disease (COPD). In a case-control study, 90 patients with COPD and 90 age- and sex- matched control subjects were included. Serum samples were tested for anti-H. pylori and anti-CagA IgG by ELISA. A physician completed a questionnaire including demographic characteristics, h

Negative / Null Result ReportOpen accessMedicine

Knowledge and perception of parents regarding halitosis in their children in Saudi Arabia

Noura A. Almadhi, Ayman M. Sulimany, Hamad A. Alzoman et al. · 2021 · Saudi Dental Journal

Objective: To evaluate parents’ knowledge about halitosis, and to compare parents’ perception of halitosis in their children to the presence of halitosis clinically. Methods: Children between 3 and 8 years attended to Dental University Hospital, King Saud University, were screened. Children satisfying inclusion criteria and their parents agreed to participate were included. Questionnaires regarding parents’ knowledge and perception about halitosis in their children were filled by attending parents. Then, the assessment of halitosis in the participating children carried out by portable gas chro

View details →DOI: 10.1016/j.sdentj.2020.08.005
Negative / Null Result ReportOpen accessSpecialties of internal medicine

Socioeconomic disadvantage and long-term survival duration in out-of-hospital cardiac arrest patients: A population-based cohort study

Dawn Yi Xin Lee, Chun En Yau, Maeve Pin Pin Pek et al. · 2024 · Resuscitation Plus

Background: Socioeconomic status (SES) is a well-established determinant of cardiovascular health. However, the relationship between SES and clinical outcomes in long-term out-of-hospital cardiac arrest (OHCA) is less well-understood. The Singapore Housing Index (SHI) is a validated building-level SES indicator. We investigated whether SES as measured by SHI is associated with long-term OHCA survival in Singapore. Methods: We conducted an open cohort study with linked data from the Singapore Pan-Asian Resuscitation Outcomes Study (PAROS), and the Singapore Registry of Births and Deaths (SRBD)

View details →DOI: 10.1016/j.resplu.2024.100610
Negative / Null Result ReportOpen accessMedicine

Effect of antacid syrup on the surface roughness and microhardness of composite materials: An <i>in vitro</i> atomic force microscopy study.

Patil PB, Chougule PG, Kamat SB et al. · 2026 · Journal of conservative dentistry and endodontics

Aim The aim of this in vitro study was to evaluate the effect of antacid syrup on surface roughness and microhardness of composites. Materials and methods Two different composite resin materials, Nanofilled and Suprananofilled were used.…

View details →DOI: 10.4103/jcde.jcde_121_26
Negative / Null Result ReportOpen accessMedicine (General)

Association of mixed exposure to lithium, vanadium, uranium, and bismuth in early pregnancy with gestational weight gain

Jiao LI, Qi LI, Shuang CHENG et al. · 2026 · 环境与职业医学

BackgroundGestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy.ObjectiveTo investigate the associa

View details →DOI: 10.11836/jeom25403
Negative / Null Result ReportOpen accessArctic medicine. Tropical medicine

Leishmania, Babesia and Ehrlichia in urban pet dogs: co-infection or cross-reaction in serological methods?

Felipe da Silva Krawczak, Ilka Afonso Reis, Julia Angélica da Silveira et al. · 2015 · Revista da Sociedade Brasileira de Medicina Tropical

INTRODUCTION: The present study was designed to assess the occurrence of co-infection or cross-reaction in the serological techniques used for detecting the anti-Leishmania spp., -Babesia canis vogeli and -Ehrlichia canis antibodies in urban dogs from an area endemic to these parasites. METHODS: The serum samples from dogs were tested for the Babesia canis vogeli strain Belo Horizonte antigen and Ehrlichia canis strain São Paulo by immunofluorescence antibody test (IFAT) and by anti-Leishmania immunoglobulin G (IgG) antibody detection to assess Leishmania infection. We used the following four

View details →DOI: 10.1590/0037-8682-0291-2014
Negative / Null Result ReportOpen accessNeurology. Diseases of the nervous system

Intracranial and extracranial artery stenosis and clinical outcome of acute ischemic stroke patients receiving intravenous thrombolysis

Yangyang Guo, Bingyang Zhang, Lianmei Zhong et al. · 2026 · Frontiers in Neurology

BackgroundIntracranial and/or extracranial atherosclerotic stenosis is a common etiology of acute ischemic stroke (AIS). This study aimed to evaluate the impact of intracranial or extracranial atherosclerotic stenosis on early neurological deterioration (END), hemorrhagic transformation (HT) and 90-day clinical outcomes in patients receiving intravenous thrombolysis.MethodsWe retrospectively enrolled patients with AIS who received intravenous alteplase (0.9 mg/kg) at the First Affiliated Hospital of Kunming Medical University between February 2019 and August 2022. Data on demographics, stroke

View details →DOI: 10.3389/fneur.2025.1700753
Negative / Null Result ReportOpen accessMedicine

Usefulness of chest radiographs in the management of acute asthma in adult asthmatics in a developing country

Piyusha Milani Atapattu, Chemindra Biyanwila, Manamalabaduge Upul Jerard Fernando · 2017 · American Journal of Experimental and Clinical Research

Chest radiographs are widely available, even in most hospitals in developing countries, and can detect a variety of lung pathologies. When adults are admitted to hospital with acute asthma, chest radiographs are often obtained. Studies on the usefulness of chest radiographs in acute asthma have shown varying results. This study aimed at evaluating the usefulness of chest radiographs in the management of acute asthma in adult asthmatics in a developing country. Plain chest radiographs performed within 24 hours of admission in 115 consecutive adult asthmatic patients (asthma defined by Asthma Ed

Negative / Null Result ReportOpen accessMedicine

Demographic risk factors for extra-pulmonary tuberculosis among adolescents and adults in Saudi Arabia.

Hawra Al-Ghafli, Bright Varghese, Mushira Enani et al. · 2019 · PLoS ONE

Despite low infectious potential of extrapulmonary tuberculosis (EPTB), it poses significant clinical challenges in terms of diagnosis and treatment monitoring. Understanding the main demographical risk factors for disease characteristics of EPTB plays a crucial role in speeding up diagnosis process and improving overall clinical experience. The aim of this study was to investigate the main demographical and clinical risk factors for EPTB among adults and adolescents for the first time in Saudi Arabia. A cross-sectional multicenter study was carried out on a collection of 902 extrapulmonary My

View details →DOI: 10.1371/journal.pone.0213846
Negative / Null Result ReportOpen accessMedicine

Red cell distribution width in relation to incidence of stroke and carotid atherosclerosis: a population-based cohort study.

Martin Söderholm, Yan Borné, Bo Hedblad et al. · 2015 · PLoS ONE

Increased red cell distribution width (RDW) has been related to poor prognosis in patients with cardiovascular disease, and is a predictor of cardiovascular mortality in the general population. The purpose of the present study was to investigate if RDW is associated with increased incidence of stroke and its subtypes in individuals from the general population.Red cell distribution width was measured in 26,879 participants (16,561 women and 10,318 men aged 45-73 years) without history of coronary events or stroke, from the population-based Malmö Diet and Cancer Study. Incidences of total stroke

View details →DOI: 10.1371/journal.pone.0124957
Negative / Null Result ReportMedicine

Gut Microbiome and Environmental Enteric Dysfunction Are Unchanged by 18 Months of Small-Quantity Lipid-Based Nutrient Supplementation among Young Children in Lusaka, Zambia.

Lauer, Leng, Chembe et al. · 2026 · The British journal of nutrition

Small-quantity lipid-based nutrient supplements (SQ-LNS) have been shown to improve growth, development, and survival among young children in low-resource settings. One hypothesized pathway is through improvements in intestinal health,…

View details →DOI: 10.1017/s0007114526107818
Negative / Null Result ReportOpen accessDermatology

Can Foot Dermatophyte Infections Signal Future Diabetes Risk? Findings from a Register-based Study

Anne Sofie Frølunde, Jan Brink Valentin, Lise Kristensen et al. · 2026 · Acta Dermato-Venereologica

Dermatophyte infections are common in general practice and occur more often in individuals with type 2 diabetes (T2D), but whether they signal undiagnosed T2D remains unclear. We conducted a register-based cohort study including positive PCR tests for dermatophyte infection from the feet or nails, matched 1:3 to individuals from the same geographic area in Denmark. Those with known diabetes, type 1 diabetes or aged under 20 were excluded. Incidence rates (IRs) and incidence rate ratios (IRRs) for new-onset T2D were estimated using Poisson regression. The final cohort comprised 78,140 individua

View details →DOI: 10.2340/actadv.v106.adv-2025-0125