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Novel drugs approved by the EMA, the FDA and the MHRA in 2025: A year in review
No full textIn the 2025 novel drug mini-review, one can take a full measure of the ingenuity that underlies current drug design and development, despite the year's smaller harvest (46 novel drugs) compared to 2024 (53) and 2023 (70). 54% of the novel drugs are first-in-class (FIC). The emphasis on proteins/antibodies is maintained (~25% novel drugs in 2025), an industry trend that does not seem to abate. Fewer than half of the novel medicines address major or common disorders. Among the FIC drugs, it is worth mentioning the Na
1.8 channel inhibitor suzetrigine, the first non-opioid approved to palliate acute pain; the first positive allosteric modulator of transient receptor potential melastatin 8 (TRPM8), acoltremon, that increases basal tear production in dry eye disease, a globally common disorder; lerodalcibep, a 'third generation' adnectin inhibitor of the protease Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) to treat elevated LDL-c; and zoliflodacin and gepotidacin, both innovatively targeting bacterial topoisomerases to treat uncomplicated urinary tract infections. Most of the approved medicines target unmet medical need areas and/or orphan indications (the latter alone accounting for 41% of the 2025 novel drugs) by applying imaginative approaches. These approaches include: the combination of two FIC drugs, the RAF/MEK clamp avutometinib paired with the FAK/Pyk2 inhibitor defactinib, to block more efficiently the RAS-RAF-MEK-ERK/FAK oncogenic pathway in low-grade serous ovarian cancer; fitusiran, the first RNAi therapy for haemophilia, targeting for the first time the production of the natural anticoagulant anti-thrombin in the liver; and brensocatib, which attenuates the activation of downstream neutrophil proteases by inhibiting the protease DPP1, thereby preventing lung tissue destruction in bronchiectasis. The landscape of novel drugs approved in 2025 reveals that pharmaceutical innovation continues to advance through FIC mechanisms, sophisticated therapeutic approaches, and a strong focus on unmet medical need
Dyspepsia Care as a Missed Gateway to Gastric Cancer Prevention in High-Risk U.S. Populations
No full textDyspepsia is among the most common gastrointestinal complaints, affecting nearly one in five adults annually. Guidelines diverge in their recommendations: the American College of Gastroenterology and Canadian Association of Gastroenterology endorse Helicobacter pylori "test-and-treat" for patients under 60 years, with upper endoscopy for those aged 60 and above or with alarm features. By contrast, the American Society for Gastrointestinal Endoscopy advises endoscopy for patients with new-onset dyspepsia beginning at age ≥ 50, even without alarm features. The British Society of Gastroenterology emphasizes risk context, recommending earlier endoscopy (age > 40 years) for individuals from regions with a high incidence of gastric cancer or with a family history of gastric cancer. These differences underscore uncertainty around age thresholds and the limitations of uniform, age-based strategies. In the United States, where several high-risk populations carry disproportionately elevated gastric cancer risk, a tailored, ethnicity- and life-course-informed approach is warranted. Embedding ancestry, nativity, and family history into dyspepsia evaluation would reframe H. pylori eradication as primary prevention and lower thresholds for endoscopy in high-risk groups. Such a strategy would rationalize endoscopy use, advance equity, and reduce preventable deaths. Reframing dyspepsia as an opportunity for prevention is both a clinical and equity imperative
SynthCharge: An Electric Vehicle Routing Instance Generator with Feasibility Screening to Enable Learning-Based Optimization and Benchmarking
No full textThe electric vehicle routing problem with time windows (EVRPTW) extends the classical VRPTW by introducing battery capacity constraints and charging station decisions. Existing benchmark datasets are often static and lack verifiable feasibility, which restricts reproducible evaluation of learning-based routing models. We introduce SynthCharge, a parametric generator that produces diverse, feasibility-screened EVRPTW instances across varying spatiotemporal configurations and scalable customer counts. While SynthCharge can currently generate large-scale instances of up to 500 customers, we focus our experiments on sizes ranging from 5 to 100 customers. Unlike static benchmark suites, SynthCharge integrates instance geometry with adaptive energy capacity scaling and range-aware charging station placement. To guarantee structural validity, the generator systematically filters out unsolvable instances through a fast feasibility screening process. Ultimately, SynthCharge provides the dynamic benchmarking infrastructure needed to systematically evaluate the robustness of emerging neural routing and data-driven approaches
Disaster Preparedness and Resource Awareness Gaps Among Families Managing Food Allergy: Findings from a Pilot Survey
No full textSingle-dose genome editing therapy rescues auditory and vestibular functions in adult mice with DFNA41 deafness
Get PDFStem Cell-based Nerve Regenerative Therapies: The Role of Adipose-Derived Stem Cells (ADSCs) in Preventing Nerve Adhesions and Promoting Axonal Nerve Repair
No full textDamage to either the central or peripheral nervous system can result in significant impairments of movement and sensation, with poor regeneration often resulting from complications such as nerve adhesion and fibrosis. Adipose-derived stem cells (ADSCs) have emerged as a promising therapeutic candidate in promoting nerve regeneration owing to their regenerative potential, abundance, ease of harvest, low immunogenicity, and anti-inflammatory properties. ADSCs, isolated from adipose tissue, can differentiate into neural lineages, secrete a broad spectrum of neurotrophic and anti-fibrotic factors, and thereby foster axonal sprouting, remyelination, and scar attenuation. Additionally, these cells have demonstrated efficacy in preventing nerve adhesion, a common complication of nerve injury that impedes functional recovery. This review explores the properties, advantages, and regenerative potential of ADSCs, highlighting their roles in promoting axonal regeneration, myelination, and reducing fibrosis. Preclinical studies and early clinical trials associated with the peripheral and central nervous system injuries have reported promising results in terms of functional recovery and reduced scar formation, but challenges remain in standardizing ADSC-based therapies and achieving full functional restoration. Future advancements in ADSC therapies may include optimized delivery systems, genetic modifications, and the integration of advanced biomaterials to enhance their regenerative capabilities
Causal machine learning reveals age-dependent radiation dose effects on mandibular osteoradionecrosis
No full textDistinguishing causal relationships from statistical correlations remains a fundamental challenge in clinical research, limiting the translation of observational findings into interventional treatment guidelines. Here we apply causal machine learning to establish causal effects of radiation dose parameters on mandibular osteoradionecrosis (ORN) in 931 head and neck cancer patients treated with volumetric-modulated arc therapy. Using generalized random forests, we demonstrate that all examined dosimetric factors exhibit significant positive causal effects on ORN development (average treatment effects: 0.092-0.141). Integration with explainable machine learning reveals substantial treatment effect heterogeneity, with patients aged 50-60 years showing the strongest causal dose-response relationships (conditional average treatment effects up to 0.229), while patients over 70 years demonstrate minimal effects. These results suggest that age-stratified treatment optimization and personalized treatment planning for the dosimetric factors could reduce ORN risk. Our findings demonstrate that causal inference methods can transform clinical retrospective radiotherapy data into personalized treatment recommendations, providing a methodological framework applicable to toxicity prediction across oncology and other clinical domains where treatment decisions depend on complex dose-response relationships
Light Filtering Lenses and Visual Photosensitivity in Individuals With Traumatic Brain Injury
No full textThe purpose of this study was to assess visual photosensitivity using the Ocular Photosensitivity Analyzer (OPA) with and without light filtering lenses in individuals with traumatic brain injury (TBI) and non-TBI controls.
This cohort study included 46 individuals with TBI (n = 46) and without TBI (n = 46) assessed from May 2021 to August 2023 at a large academic tertiary center. Visual photosensitivity thresholds (VPTs) were measured at two visits (≥1 month apart) under four lens conditions: no lens (NL), plano lenses (PLs), FL-41 lenses (FLs), and gray-filtering lenses (GLs). Lower VPTs indicate greater visual photosensitivity.
Participants with TBI had significantly lower VPTs compared with non-TBI controls across all lens conditions at the initial visit (TBI: PL = 1.6 ± 0.9, FL = 1.9 ± 0.9, and GL = 1.9 ± 1.0; and non-TBI: PL = 2.5 ± 0.9, FL = 2.8 ± 0.9, and GL = 2.8 ± 0.9 log lux, P 0.80 for all conditions).
Individuals with TBI consistently demonstrated greater visual photosensitivity compared with controls. FL and GL light filtering lenses improved light tolerance for both groups. These results highlight visual photosensitivity as a TBI sequela and suggest that these light filtering lenses may serve as effective treatment options
Party Pressure and Representation
No full textI study how political parties affect representation in the U.S. House. To do so, I account for party pressure on the votes of members in an otherwise standard spatial model that uses roll call voting patterns to identify member ideologies. I simultaneously estimate voter ideologies from survey responses, leveraging their responses on issues before Congress to bridge voters and members into the same ideological space. I find that, relative to a model without party pressure, member ideologies and those of their constituents are much more closely aligned. The results imply that, in terms of actual votes, parties drive a wedge between members and those they represent. I provide evidence that parties do so strategically, balancing the need for legislative wins and the electoral concerns of their member
