Negative / Null Result ReportOpen accessMathematics
Yong Li, Henry Sun, Zuoli Zhang · 2025 · Pharmaceutics
Background: Physiologically based pharmacokinetic (PBPK) modeling is a mathematical approach that integrates human physiological parameters with drug-specific characteristics (including both active pharmaceutical ingredients and excipients), and it has emerged as one of the core technologies for optimizing the efficiency and reliability of drug development. Methods: This study synthesizes applications of PBPK models in FDA-approved drugs (2020–2024), systematically analyzing model utilization frequency, indication distribution, application domains and choice of modeling platforms, to reveal th
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Luyuan Chang, Yang Liu, Haipeng Li et al. · 2025 · Frontiers in Cellular and Infection Microbiology
Cirrhosis remains a significant global health burden, causing approximately 1.4-1.5 million deaths each year and contributing to nearly 46 million disability-adjusted life years (DALYs) worldwide. Increasing evidence identifies the gut-liver axis as a central driver of disease progression, wherein intestinal dysbiosis, barrier disruption, and microbe-derived metabolites collectively exacerbate inflammation, fibrogenesis, and related complications. Across more than 40 recent studies, gut microbial α-diversity declined by 30-60%, and over 80% reported a marked depletion of short-chain fatty acid
View details →Negative / Null Result ReportOpen accessMedicine
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…
View details →Negative / Null Result ReportOpen accessPharmacology, Toxicology and Pharmaceutics
Abdurrahman M. Fahmy, Osama Saher, Heba Attia et al. · 2026 · AAPS PharmSciTech
Abstract This study introduces and statistically optimizes novel Tetra-Synergistic Bilosomes (TSB), an advanced nano-platform for topical delivery of voriconazole (VOR) in otomycosis therapy. The term “Tetra-Synergistic” reflects the incorporation of four complementary components: Cremophor® EL, sodium deoxycholate, Brij® 58, and Brij® S2, working in synergy to enhance therapeutic efficacy. TSB was fabricated using the thin-film hydration method and optimized through a 2 3 D-optimal design. Three formulation factors were investigated: Cremophor® EL: VOR ratio, sodium deoxycholate: cholesterol
View details →Negative / Null Result ReportOpen accessImmunology and Microbiology
Marcello Candelli, Marta Sacco Fernandez, Gloria Rozzi et al. · 2025 · Diagnostics
Background and Objectives: Despite major advances in medical science and critical care, sepsis remains a leading cause of morbidity and mortality worldwide: it arises from dysregulated host response to infections and may culminate in organ dysfunction. A hallmark of its pathogenesis is the cytokine storm, in which interleukins (ILs) serve as central mediators of both protective and deleterious immune responses. This review summarizes the current knowledge on the role of ILs in sepsis, emphasizing their potential as biomarkers and therapeutic targets. Material and Methods: We analyzed recent cl
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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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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—
View details →Negative / Null Result ReportOpen accessPharmacology, Toxicology and Pharmaceutics
Suelen Gauna Trindade, Fernando Bonin Okasaki, Ashley P. Williams et al. · 2025 · Journal of Colloid and Interface Science
The self-assembly of glycyrrhizic acid (GA) in aqueous solutions has significant implications for soft matter science and material design. Here, we describe the self-assembly of GA under well-defined conditions, focusing on measurements of the critical aggregation concentration (CAC) - when GA dimers start stacking into nanofibrils, and of the critical gel concentration (CGC) - when nanofibrils entangle into a viscoelastic network. We examine in detail the structure at low concentrations and its evolution into a viscoelastic hydrogel, addressing the kinetic pathway. We highlight the dependence
View details →Negative / Null Result ReportOpen accessSocial Sciences
Junhua Dang, Zeynep E. Ekim, Sarah Ohlsson et al. · 2020 · BMC Psychology
BACKGROUND: Previous studies showed that anger, rather than sadness, created automatic intergroup bias in a minimal group context. METHODS: The current research reports a single study (N = 99) aiming to replicate this finding and further to test whether the intergroup bias manifests as ingroup favoritism, outgroup derogation, or both. RESULTS: Our results failed to replicate the effect of anger on automatic bias. Intriguingly, participants across all emotion conditions exhibited high level of ingroup favoritism, but there was little evidence of outgroup derogation. CONCLUSION: These results su
View details →Negative / Null Result ReportOpen accessMedicine
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…
View details →Negative / Null Result ReportOpen accessNeuroscience
Evgeny A. Ermakov, Irina A. Mednova, Anastasiia S. Boiko et al. · 2025 · Journal of Integrative Neuroscience
Neuroinflammation, meaning an inflammatory process primarily occurring within the central nervous system (CNS), is thought to be associated with the pathogenesis of psychiatric disorders including schizophrenia (SC), although existing evidence is sometimes contradictory. This review critically summarizes the existing data on neuroinflammation and possible neuroinflammatory mechanisms in the pathogenesis of SC. Despite heterogeneity and inconsistency, the existing evidence indicates dysregulation of inflammatory genes and infiltration of the CNS parenchyma by immune cells, disturbances in the b
View details →Negative / Null Result ReportOpen accessNeuroscience
James Downar, James Downar, Julie Lapenskie et al. · 2024 · Palliative Medicine
Background: Psychological and existential suffering affects many people with advanced illness, and current therapeutic options have limited effectiveness. Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective therapy…
View details →Negative / Null Result ReportOpen accessNeuroscience
Olivier Senn, Florian Hoesl, Toni Bechtold et al. · 2024 · PLoS ONE
There is a broad consensus in groove research that the experience of groove, understood as a pleasurable urge to move in response to music, is to some extent related to the complexity of the rhythm. Specifically, music with medium rhythmic complexity has been found to motivate greater urge to move compared to low or high complexity music (inverted-U hypothesis). Studies that confirmed the inverted-U hypothesis usually based their measure of complexity on the rhythmic phenomenon of syncopation, where rhythms with more and/or stronger syncopation are considered to be more complex than less synco
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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…
View details →Negative / Null Result ReportOpen accessEnvironmental Science
Yuchen Suo, Tong Li, Christian von Sperber et al. · 2025 · Biogeochemistry
Abstract The stability of carbon (C) stocks in peatlands is intricately linked to phosphorus (P) bioavailability. Given that organic P compounds (P o ) can make up to 89% of total soil P in these ecosystems, it is vital to understand their role in regulating plant productivity and organic matter decomposition. Despite this significance, the mechanisms controlling P bioavailability remain poorly understood. Plants and soil microorganisms primarily regulate the release of soil P via low-molecular-weight organic acids (LMWOAs) and modulate the hydrolysis of P o through phosphatase enzymes, partic
View details →Negative / Null Result ReportOpen accessMedicine
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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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…
View details →Negative / Null Result ReportMedicine
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…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Fanzhuo Xu, Yu Xie, Weiwei Yu et al. · 2026 · Frontiers in Microbiology
Multidrug resistance in Gram-negative bacteria has become a significant global public health challenge, threatening human health and clinical treatment outcomes. The unique outer membrane structure of these pathogens greatly limits antibiotic penetration, serving as the core mechanism of resistance. This paper systematically analyses antimicrobial strategies targeting the outer membrane of Gram-negative bacteria, mainly including: (1) directly disrupting the outer membrane structure and enhancing drug permeability; (2) inhibiting the biosynthesis or transport pathways of key outer membrane com
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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…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Vasilios Liapis, Aneta Zysk, Mark DeNichilo et al. · 2017 · Cancer Medicine
Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, hypoxia also leads to treatment opportunities as demonstrated by the development of compounds that target regions of hypoxia within tumors. Evofosfamide is a hypoxia-activated prodrug that is created by linking the hypoxia-seeking 2-nitroimidazole moiety to the cytotoxic bromo-isophosphoramide mustard (Br-IPM). When evofosfamide is delivered to hypoxic regions of tumors, the DNA cross-linking toxin, Br-IPM, is released leading to cell death. This study assessed the anticancer efficacy of evofosfamide in
View details →Negative / Null Result ReportMedicine
Xu Yang, Lina Zhao, Anhui Shi et al. · 2023 · The American Journal of Gastroenterology
INTRODUCTION: Adjuvant radiotherapy is recommended for pT1b esophageal squamous cell cancer (ESCC) after endoscopic submucosal dissection (ESD). However, it is unclear whether additional radiotherapy can improve patient survival. This…
View details →Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology
Hiroki Isono, Taiju Miyagami, Kohta Katayama et al. · 2016 · Internal Medicine
Tetanus is a potentially fatal infection. Approximately 100 cases are reported in Japan each year; however, little is known about its clinical course and outcomes in the current era of treatment. We herein report three cases of tetanus in…
View details →Negative / Null Result ReportOpen accessMedicine
Timothy S. Pardee, Bayard L. Powell, Richard A. Larson et al. · 2024 · Blood Neoplasia
Acute myeloid leukemia (AML) is an aggressive cancer of the myeloid lineage. Outcomes in older patients are poor with high rates of resistant and relapsed disease. Devimistat is a lipoic acid analog that inhibits mitochondrial metabolism.…
View details →Negative / Null Result ReportOpen accessMedicine
Nadine Haase, Julianna Rugor, Łukasz Przybył et al. · 2014 · PLoS ONE
Relaxin is a corpus-luteum produced protein hormone with vasodilatatory, anti-fibrotic, and angiogenic properties that are opposite to angiotensin (Ang) II. We investigated whether or not relaxin ameliorates Ang II-induced target-organ damage. We used double transgenic rats harboring both human renin and angiotensinogen genes (dTGR) that develop severe hypertension, target-organ damage, and die untreated within 7-8 weeks. Recombinant relaxin at a low (26 μg/kg/d) and a high dose (240 μg/kg/d) was given to 4 week-old dTGR and age-matched Sprague-Dawley rats (SD). Systolic blood pressure increas
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Luís Alberto de Pádua Covas Lage, Rita Novello de Vita, Lucas Bassolli de Oliveira Alves et al. · 2024 · Cancers
Background: Diffuse large B-cell lymphoma (DLBCL) especially affects the older population. Old (≥60 years) and very old age (≥80 years) DLBCL patients often present high-risk molecular alterations, lower tolerability to conventional immunochemotherapy, and poor clinical outcomes. In this scenario, attenuated therapeutic strategies, such as the R-MiniCHOP and R-MiniCHOP of the elderly regimens, have emerged for this particularly fragile population. However, the responses, clinical outcomes, and toxicities of these regimens currently remain poorly understood, mainly because these individuals are
View details →Negative / Null Result ReportOpen accessMedicine
Masatoshi Uchida, Toshikazu Abe, Kazuyuki Ono et al. · 2017 · Acute Medicine & Surgery
Aim Our aim was to evaluate the effect of ulinastatin on 28‐day mortality in patients who developed multiple organ failure ( MOF ) related to their acute illness and were admitted to the intensive care unit ( ICU ). Methods We carried out a retrospective observational study of MOF patients in a general ICU of a tertiary care hospital in Japan from January 2009 to December 2012. The primary outcome was 28‐day all‐cause mortality. Secondary outcomes were ventilator‐free days, ICU ‐free days, and vasopressor‐free days at day 28. We investigated the association between ulinastatin treatment and ou
View details →Negative / Null Result ReportMedicine
Shahid Habib, Nehali Patel, Sandeep Yarlagadda et al. · 2018 · Journal of Gastroenterology and Hepatology
BACKGROUND AND AIM: Infection is a leading precipitant of acute-on-chronic liver failure. This study aims to determine the safety and efficacy of antibiotics within acute-on-chronic liver failure. METHODS: Retrospective study of 457…
View details →Negative / Null Result ReportOpen accessMedicine
Mathilde Ruggiu, Bruno Cassinat, Jean‐Jacques Kiladjian et al. · 2020 · Biology of Blood and Marrow Transplantation
BCR-ABL-negative myeloproliferative neoplasms (MPNs) in transformation have a dismal prognosis, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the sole curative therapeutic option. We retrospectively…
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Vikash Agrawal, Satyan Lakshminrusimha, Praveen Chandrasekharan · 2019 · Children
The International Liaison Committee on Resuscitation (ILCOR) recommends the initiation of chest compressions (CC) during neonatal resuscitation after 30 s of effective ventilation if the infant remains bradycardic (defined as a heart rate…
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