Pharmacokinetic and Exposure-Response Modeling Support Body Surface Area-Based Dosing of Farletuzumab Ecteribulin in Japanese Patients with Solid Tumors.

The first-in-human, Phase 1 Study 101 showed antitumor activity and a tolerable safety profile of farletuzumab ecteribulin in Japanese patients with platinum-resistant ovarian and non-small cell lung cancer. A pharmacometric assessment evaluated farletuzumab ecteribulin pharmacokinetics and exposure-response (E-R) relationships for efficacy and safety to support dose optimization. Patients received 0.

Nitrogen fixation may not alleviate stoichiometric imbalances that limit primary production in eutrophic lake ecosystems.

Ecosystem-scale primary production may be proximately limited by nitrogen (N) but ultimately limited by phosphorus (P) because N fixation contributes new N that accumulates relative to P at ecosystem scales. However, the duration needed to transition between proximate N limitation and ultimate P limitation remains unknown for most ecosystems, including lakes. Here we present the results of a fully replicated, multi-annual lake mesocosm experiment that permitted full air-water-sediment interactions that mimicked lake ecosystem ecology.

Overcoming low status or maintaining high status? A multinational examination of the association between socioeconomic status and honour.

We examined the relationship between socioeconomic status (SES) and endorsement of honour. We studied the SES-honour link in 5 studies (N = 13,635) with participants recruited in different world regions (the Mediterranean and MENA, East Asian, South-East Asian, and Anglo-Western regions) using measures that tap into various different facets of honour. Findings from these studies revealed that individuals who subjectively perceived themselves as belonging to a higher (vs.

Extended Treatment Duration of Artemether-Lumefantrine in Ugandan Children with HIV on Efavirenz-Based Antiretroviral Therapy: A Randomized Controlled Pharmacokinetic and Pharmacodynamic Trial.

Malaria and HIV co-infection are prevalent in sub-Saharan Africa causing significant drug interactions with co-treatment. We previously reported a 30%-70% reduction in exposure to the standard 3-day (6-dose) artemether-lumefantrine (AL) treatment for malaria when given with efavirenz-based HIV therapy, impacting malaria reinfection risk. We conducted a prospective, randomized study comparing the 3-day regimen to an extended 5-day (10-dose) regimen with pharmacokinetic sampling for artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine (DBL) over 42 days.

Communicating scientific evidence: drugs for Alzheimer's disease as a case study.

This paper reviews the scientific evidence on new anti-amyloid monoclonal antibodies for treating Alzheimer's disease as a case study for improving scientific evidence communication. We introduce five guidelines condensed from the biomedical evidence literature but adapted to the short format of science communication in e.g.

Association of Menopause and Rhinitis Among Adult Women in the United States: Findings from the All of Us Research Program.

Objective: The inflammatory role of female hormones has been garnering increased attention in the literature. Studies suggest a link between estrogen and inflammatory conditions of the airways and nasal mucosa. However, there remains a paucity of literature regarding the associations of hormones with rhinitis.

Tailoring the oxidation of benzyl alcohol and its derivatives with (photo)electrocatalysis.

The electrochemical oxidation of alcohol molecules has gained significance as a key anode reaction, offering an alternative to the oxygen evolution reaction (OER) for hydrogen (H) production and carbon dioxide (CO) reduction. The (photo)electrochemical oxidation of benzyl alcohol and its derivatives serves as an important model system, not only because benzyl alcohol oxidation is a critical industrial process, but also because it offers valuable insights into electrocatalytic biomass conversion. Tailoring this reaction through electrochemical and photoelectrochemical methods using heterogeneous noble and transition metal electrocatalysts presents a green approach and the potential for uncovering new reaction mechanisms.

Relationships for Social Change: The Value of the Promotora Framework in Navigating Systems of Employment.

In the United States, socioeconomic disparities are a reality that shapes the challenges many communities of color experience. Throughout the globe, community-based initiatives have been explored as a way to reduce several barriers that contribute to social inequalities. One in particular, the Promotora framework, has been widely used to improve health outcomes.

Symptomatic Improvement in Adults and Adolescents With Eosinophilic Esophagitis Requires Higher Systemic Dupilumab Exposure Than Histologic Response.

Introduction: We assessed potential mechanisms behind the requirement for more frequent dupilumab dosing in eosinophilic esophagitis (EoE) compared with other approved indications.

Methods: Results for the phase 3 LIBERTY EoE TREET study coprimary endpoints (proportion of patients achieving a peak intraepithelial eosinophil count of ≤6 eosinophils per high-power field and absolute change from baseline in Dysphagia Symptom Questionnaire total score) were pooled in exposure-response analyses.

Results: A steep initial relationship then plateau was observed between higher dupilumab steady-state trough concentrations and decreased eosinophilic infiltration at week 24, whereas a graded exposure-response relationship was observed for symptomatic improvement at week 24.

International Validation of a Novel PEACE Scale to Improve the Quality of Upper Gastrointestinal Mucosal Inspection During Endoscopy.

Introduction: The performance of a high quality esophagogastroduodenoscopy (EGD) is dependent on the mucosal cleanliness. Recently, the Polprep: Effective Assessment of Cleanliness in EGD (PEACE) scale was created to assess the degree of mucosal cleanliness during EGD. The aim of this study was to validate this scoring system in a cohort of international endoscopists.

Alcohol-induced liver injury is mediated via α4-containing nicotinic acetylcholine receptors expressed in hepatocytes.

Background: Our previous study demonstrated that alcohol induced the expression of the α4 subunit of nicotinic acetylcholine receptors (nAChRs) in the livers of wild type mice (WT), and that whole-body α4 nAChR knockout mice (α4KO) showed protection against alcohol-induced steatosis, inflammation, and injury. Based on these findings, we hypothesized that hepatocyte-specific α4 nAChRs may directly contribute to the detrimental effects of alcohol on the liver.

Methods: Hepatocyte-specific α4 knockout mice (α4HepKO) were generated, and the absence of α4 nAChR was confirmed through PCR of genomic DNA.

Survival, Tumor Control, and Safety Outcomes of Proton Therapy in Sinonasal Cancer Population: A Systematic Review and Meta-Analysis.

Background: In sinonasal cancer (SNC), treatment with proton therapy (PT) provides excellent local control, especially after gross total resection. Because of the heterogeneity and rarity of this disease site, a comprehensive assessment of toxicity, survival, and control rates is lacking. Our primary objective was to assess the toxicity outcomes of PT in SNC patients, with a secondary aim of assessing survival and tumor control after PT.

A review of ectochondral bone and the role of membranes in shaping endochondral bones of the skull.

Bones of the skull are traditionally categorized as derived from either endochondral or intramembranous bone. In our previous work, we have observed the interaction of different tissue types in growth of the skull. We find the dichotomy of intramembranous and endochondral bone to be too restrictive, limiting our interpretation of sources of biological variation.

Inhibition of acyl-CoA synthetase long-chain isozymes decreases multiple myeloma cell proliferation and causes mitochondrial dysfunction.

Multiple myeloma (MM) is an incurable cancer of plasma cells with a 5-year survival rate of 59%. Dysregulation of fatty acid (FA) metabolism is associated with MM development and progression; however, the underlying mechanisms remain unclear. Herein, we explore the roles of long-chain fatty acid coenzyme A ligase (ACSL) family members in MM.

Enhancing surface energy and characterizing optical properties of ultra-high translucency zirconia via an innovative heat treatment process.

Purpose: Ultra-high translucency zirconia (UT-Zr) is known for its high esthetic quality; however, its inert surface results in low hydrophilicity and surface energy (SE). To address this limitation, this study proposes an innovative zirconia heat treatment process (ZHTP) and aims to evaluate the effects of ZHTP on the surface characteristics of UT-Zr, offering a novel and practical approach for surface pretreatment in dental practice.

Material And Methods: The plate-shaped UT-Zr samples were fabricated.

A phase 2 basket study of talabostat, a small-molecule inhibitor of dipeptidyl peptidases, administered in combination with pembrolizumab in patients with advanced solid cancers.

Background: Talabostat, an oral small molecule inhibitor of dipeptidyl peptidases (DPP4 and DPP8/9), has shown synergistic activity with immune checkpoint inhibitors in preclinical studies. This open label, phase 2 basket trial assessed the antitumor activity of combining talabostat and pembrolizumab (anti-programmed death-1 antibody) in advanced solid tumor patients.

Methods: The primary objective was assessment of dose-limiting toxicity (DLT) rates in the first six patients (lead-in stage) and response rate (efficacy stage; included cohort A [checkpoint inhibitor (ICI) naive] and cohort B [ICI pretreated]) for the study treatment using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.

Moral Complexity in Traffic: Advancing the ADC Model for Automated Driving Systems.

The incorporation of ethical settings in Automated Driving Systems (ADSs) has been extensively discussed in recent years with the goal of enhancing potential stakeholders' trust in the new technology. However, a comprehensive ethical framework for ADS decision-making, capable of merging multiple ethical considerations and investigating their consistency is currently missing. This paper addresses this gap by providing a taxonomy of ADS decision-making based on the Agent-Deed-Consequences (ADC) model of moral judgment.

Anxiety Symptoms Predict Subsequent Depressive Symptoms in Neurodivergent Youth: A 10-Year Longitudinal Study.

Neurodivergent youth often experience anxiety and depressive symptoms that may hamper adaptive functioning and well-being. There is little knowledge of how anxiety and depression are related in neurodivergent youth. Therefore, we aimed to examine whether the relationship between anxiety and depressive symptoms is uni- or bidirectional in neurodiverse youth.

Temporal Tendencies: Exploring the Impact of Chronotype Timing on Youth Depression Risk.

Developmental changes in youth sleep preferences (chronotype) and pubertal development are consequential for youth risk for depression. Previous research has identified individual differences in chronotype in risk for psychopathology. However, little is known regarding how the timing of chronotype may confer risk in youth.

Gender Differences in Barriers in Career Development Among a Cohort of Dental Researchers. A Cross-Sectional Study.

Background: This cross-sectional study investigated gender differences in barriers to career development among dental researchers and between academic and non-academic women.

Methods: An anonymous 34-item survey assessing barriers to career development and workplace obstacles (14 items), along with demographic/occupation characteristics (22 items), was distributed among dental researchers at the Women In Science Network meetings at 2024 AADOCR/IADR General Session (QR code) and through AADOCR/IADR discussion board (online platform). Differences in barriers and workplace obstacles were analyzed between women and men with chi-square tests; comparisons were repeated among women working within versus outside academia.

Treatment Patterns and Economic Burden of Ulcerative Colitis in Japan: A Retrospective Claims Analysis.

Introduction: This retrospective claims analysis characterized contemporary ulcerative colitis (UC) treatment patterns and investigated the economic burden of UC in Japan.

Methods: This study used anonymized claims data in the Medical Data Vision database. Patients were included if they had a confirmed UC diagnosis and ≥ 1 claim of systemic treatment for UC (index date) between June 2018 and December 2022, in addition to continuous enrollment for ≥ 6 months before and ≥ 12 months after the index date.

A new model-based approach for estimating rural hospital markets.

Purpose: To provide a new approach for defining rural hospital markets.

Methods: First, we estimated models of hospital choice. We defined hospitals in the choice set using nationwide hospital data from the Healthcare Cost Report Information System (HCRIS).