Despite decades of development in anti-seizure medications, ~30% of individuals remain refractory to all treatments, and none of the existing therapies are disease modifying. Identifying targets outside the current preclinical paradigm is critically important. This study aimed to characterize the landscape of current epilepsy treatments at the level of gene interaction networks and identify novel genetic modifiers of epilepsy as potential novel therapeutic targets. We performed a functional network analysis to score genes based on their interactions with known epilepsy genes, and we integrated these functional scores with population genetics data and drug tractability information. In parallel, we performed a meta-analysis of genome-wide association studies of epilepsy-related phenotypes in genetically diverse mice using a large compendium of historical phenotyping data. Genes within mapped loci were prioritized based on functional rankings, and genomic evolutionary rate profiling (GERP) was used to identify highly single-nucleotide polymorphisms at evolutionarily constrained positions. Functional network analyses of known epilepsy genes revealed a strong involvement of neurodevelopmental processes in epilepsy pathogenesis, which are not targeted by existing or emerging treatments. Meta-analysis of seizure traits in mice identified 118 non-overlapping loci harboring potential seizure phenotype modifiers. Using functional rankings, we prioritized 168 candidate genes within these loci and used GERP scores to filter down to 75 SNPs as candidate variants within these genes. Among them, five genes-Ephb2, En2, Cadps2, Igsf21, and Cep170-contain regulatory variants in evolutionarily constrained sites. Four of these genes are validated as modifiers of neurological traits, including epilepsy susceptibility. This study prioritized epilepsy modifier genes that are strongly predicted to influence neurodevelopmental processes, which are underrepresented among current therapeutic targets. Furthermore, the identified genes represent novel candidate modifiers with potential clinical relevance. Our systems-level analysis offers a novel view into the potential target landscape, pointing toward promising new directions for disease-modifying treatments.

Gold nanoparticles have long been explored for their potential in medical diagnostics, drug delivery, and imaging, particularly in oncology. However, successful translation to clinical applications requires a deep understanding of their biomolecular interactions and transport mechanisms across cellular barriers and within cells. In this review, we examine the current understanding of the journey of gold nanoparticles from systemic administration to tumour infiltration. Specific focus is placed on the biological barriers crossed and the mechanisms involved in traversing those barriers, including active and selective transport pathways, like transcytosis, increasingly recognised as critical for nanoparticle translocation across endothelial and tumour barriers. We stratify the nanoparticle journey into smaller stages and critically discuss the most relevant in vitro models used to study each stage in isolation. Although traditional 2D cell cultures have provided some fundamental insights, more advanced tissue culture models outlined in this review offer enhanced physiological relevance. Monitoring nanoparticle behaviour within these models cannot be achieved without sophisticated imaging and quantification techniques. Herein, we have identified the most appropriate detection methods and their suitability for being used on each in vitro model for the detection of label-free gold nanoparticles. Using label-free nanoparticles preserves their native physicochemical properties and avoids potential artefacts introduced by fluorescent or radioactive tags, and conveniently, gold lends itself well to label-free detection due to its unique optical and electronic properties. By integrating insights from advanced in vitro modelling and cutting-edge detection strategies, this review highlights the current landscape and future directions for optimising the study of gold nanoparticle delivery across barriers in cancer nanomedicine.

Personalized cancer vaccines represent a revolutionary frontier in oncology, harnessing the unique genetic and molecular profile of individual tumors to elicit targeted immune responses. This review provides a comprehensive overview of the current landscape and future perspectives of neoantigen-based personalized cancer vaccines, encompassing peptide, mRNA, DNA, autologous dendritic cell, and viral or bacterial vector platforms. We further discuss the integration of immune adjuvants, delivery systems, and combinational strategies, particularly with immune checkpoint inhibitions, to overcome tumor-induced immune exhaustion and improve therapeutic efficacy. Despite significant clinical progress over the past decade in this space, major challenges remain in immunogenic neoantigens prediction, streamlining individualized vaccine manufacturing, and optimization of combinational regimens to maximize durable antitumor responses. By reviewing recent preclinical and clinical studies on neoantigen-based cancer vaccines, this review highlights key advances, identifies persistent translational bottlenecks, and underscores the need for biomarker-guided mechanistically informed trials to fully unleash the clinical potential of neoantigen-based personalized cancer vaccines in the era of precision immuno-oncology.

ABSTRACT There is strong evidence that design for remanufacturing (DfRem) can reduce initial‐design carbon emissions by up to 30%, and that product design can critically affect remanufacturing feasibility, yet academic adoption of DfRem remains limited. The last major review of DfRem dates to 2011, despite substantial evolution across environmental, economic, technological, and methodological domains. Through a review of 174 publications, this study maps the current DfRem research landscape and proposes a systematic framework approach to guide future research directions. Review findings reveal a transition from DfRem research addressed within conventional design challenges and tool development priorities, to data‐driven, sustainability‐motivated methodologies and studies. Clear emphases on OEM perspectives and the automotive sector are also identified. Notably, recent exploration and integration of Industry 4.0 technologies into DfRem research, that is, via digital twins, smart remanufacturing, and cyber‐physical systems, marks a significant and evolving shift that is logical in the context of OEM case studies. Methodologies used to study these innovations are founded upon, and increasingly aligned with eco‐design, life‐cycle assessment, and human‐centric frameworks. Methodologically, DfRem research is evolving from conceptual and secondary‐data studies toward empirical, validated research predominantly conducted as case studies, while a strong emphasis on technical engineering perspectives persists. Two resulting frameworks are presented to capture diverse perspectives related to emergent research priorities for DfRem on the basis of process versus product research focus, and analysis versus design research focus. Through the course of this review, we demonstrate DfRem as an increasingly relevant and critical enabler for the advancement of operationalized circular economy, lifecycle extension, and net‐zero strategies within sustainable manufacturing systems, and present our recommendations for continued progress, accordingly.

Generative artificial intelligence (AI) is rapidly transforming scientific publishing, offering new opportunities in surgical planning, imaging, and research. Plastic surgery's reliance on visual documentation creates unique ethical and methodological challenges, yet the extent of generative AI policy adoption in specialty journals is unclear. We reviewed author guidelines from 30 leading plastic surgery journals (April 24, 2025) identified through the 2023 Journal Citation Reports, SCImago Journal Rank, and Google Scholar Metrics. Two reviewers independently assessed each journal for generative AI policy presence and characteristics, including permitted uses, disclosure requirements, authorship restrictions, and geographic distribution. Fourteen journals (46.7%) had generative AI-related policies, most prohibiting AI authorship (85.7%) and allowing language assistance. Disclosure requirements were inconsistent, only 28.6% explained how to disclose use, and 64.3% specified a disclosure location. References to large language models or AI-generated images appeared in 28.6% of policies and 35.7% required naming the tool used. Policies were more common among US-based journals (64.3%) and absent in South America and Africa. This study presents the first specialty-specific analysis of generative AI use policies in plastic surgery journals. Fewer than half of major plastic surgery journals have generative AI policies, with significant variation in scope and global disparities that may create inequitable publication standards. Specialty-specific guidelines addressing AI-generated visual content, surgical planning, and aesthetic analysis are needed to maintain transparency and research integrity while enabling safe, ethical integration of generative AI into plastic surgery research. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Parkinson's disease in transition: Genetics, biomarkers, and emerging therapeutics.

Allogeneic hematopoietic cell transplantation is a potentially curative therapy for patients with both malignant and nonmalignant disorders. To select the optimal donor for allogeneic hematopoietic cell transplantation, the first step is to search for a matched sibling donor or a matched unrelated donor, both of which yield comparable outcomes in the current clinical landscape. Additional donor options include haploidentical donors, mismatched unrelated donors, and umbilical cord blood donors. Newer transplant approaches have refined the use of these donor sources to improve outcomes. Beyond human leukocyte antigen compatibility, several non-human leukocyte antigen factors influence optimal donor selection. These include donor age, the presence of donor-specific antibodies, cytomegalovirus status, and ABO blood type compatibility. Various graft engineering strategies have been developed. These include posttransplant cyclophosphamide, T-cell depletion techniques such as CD34+ selection, CD45RA depletion, and αβ T-cell depletion, T regulatory purification, and umbilical cord blood expansion. Optimizing the cell dose used in transplantation is also critical to improving outcomes. All of these strategies combined allow nearly every patient to find a donor with continued improvements in outcomes.

Combination therapies in acute myeloid leukemia (AML) are an area of current investigation due to the potential of overcoming resistance by targeting multiple pathways simultaneously. Triplet therapies combining hypomethylating agents, venetoclax, and targeted inhibitors are emerging as a promising therapy for older patients with AML unfit for intensive chemotherapy. These regimens have predominantly been studied in FLT3- and IDH1/2-mutated AML with attainment of high rates of measurable residual disease-negative composite remissions. Notably, patients with FLT3-internal tandem duplication and IDH1-mutated AML appear to garner a significant benefit from combination treatment due to poor duration of response to hypomethylating agents/venetoclax alone. While effective, the need to remain on indefinite therapy for individuals who are not stem cell transplant candidates and dose optimization/de-escalation strategies remain critical concerns. Herein, we aim to review the current treatment landscape of newly diagnosed and relapsed/refractory FLT3- and IDH1/2-mutated AML and the role of triplet regimens in these molecular subgroups.

T-cell engaging immunotherapies have transformed the treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL). First revolutionizing outcomes for relapsed and refractory disease, these therapies are now being incorporated and studied in the frontline setting. With the US Food and Drug Administration (FDA) approval of the CD19-directed bispecific T-cell engager (BiTE) blinatumomab for remission consolidation, the majority of patients with B-ALL receive blinatumomab in frontline therapy. Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 is FDA approved for pediatric patients with B-ALL that is refractory or in second or greater relapse. With the same target, similar mechanisms of action, and some overlap in indications, the optimal placement and sequence of these immunotherapies remain unclear. Here we review the recent data and expanded use of blinatumomab and CAR T-cell therapy and discuss the role of CAR T-cell therapy in the current pediatric B-ALL treatment landscape, including in populations with relapsed/refractory disease and at very high risk of relapse.

The beginning of precision medicine has come to rise in a new era of targeted therapies. Among these innovations, light-activatable antibody photo drug conjugates/photoimmunoconjugates termed as "PhotoBodies" have emerged as next-generation theranostic agents. By remaining inert until irradiated with a specific wavelength, PhotoBodies offer controlled diagnosis or treatment of diseased cells, tissues, or organs. This review aims to summarize the evolution of new generation of photosensitizers, linkers, and antibody formats employed in PhotoBodies, to assess current preclinical and clinical developments, to identify unaddressed challenges, and propose a roadmap for future PhotoBodies. We conducted a comprehensive literature survey focusing on studies reporting the designing and theranostic applications of PhotoBodies in both preclinical models and clinical trials. More than 15 PhotoBodies are currently in clinical trials for targeted diagnosis and two for therapeutic application in cancers. PhotoBodies have also demonstrated their flexibility to combat the silent pandemic of the world i.e., non-oncological. Advances in photosensitizer chemistry have improved photostability, singlet-oxygen quantum yield, and tissue penetration. From conventional antibodies (full length antibodies/mAb) to non-conventional antibodies (antibody fragments including Fab, F(ab')₂, scFv, diabodies, minibodies, and single-domain antibodies), all the formats have been explored to balance the pharmacokinetics of PhotoBodies with tissue accessibility. PolyBodies® based antibody partners in PhotoBodies have begun to enhance the clinical utility of PhotoBodies by improving their targeting efficacy. However, promising future includes key hurdles such as optimizing light delivery in deep tissues, managing immunogenicity, standardizing conjugation protocols, and navigating regulatory pathways. PhotoBodies represent a promising frontier in precision theranostics by combining the specificity of antibody targeting with the controllability of photochemistry. Continued refinement of photosensitizer, linkers and antibody engineering will accelerate the clinical translation of PhotoBodies and realize their full potential in next-generation precision medicine. PolyBodies (containing polyvalent and polyspecific) based antibody carriers possess an upper hand in changing the current landscape of PhotoBodies and redefine their future.

Recent update on the development of EZH2 inhibitors and degraders for cancer therapy.

Obesity is common, affecting >40% of Americans and increasing at rapid rates worldwide. Defined by the presence of excess body fat, obesity is tied to a multitude of poor health conditions, including cardiovascular disease, insulin resistance, and malignancy. Although lifestyle modifications such as diet and physical activity are cornerstones of management and crucial to enhance the health benefits achieved via targeted treatment plans, highly efficacious obesity medications are also now available. In particular, glucagon-like peptide-1 receptor agonists, have been found to be safe and efficacious, inducing clinically significant weight loss that is sustainable. Their effect on nutrition status is still being defined. In addition to medications, bariatric endoscopy and bariatric surgery are also highly effective options for durable weight loss, although these treatments are associated with malnutrition if they are not appropriately monitored. This review aims to define the current landscape of obesity medicine today, highlighting both current therapies and discussing their associated nutrition considerations, to educate the nutrition-focused provider. Multimodal therapies, combining medications and procedures, are an active area of research and will likely define care in future years.

Corneal disorders are among the leading causes of visual impairment worldwide, with corneal transplantation historically serving as the cornerstone of surgical treatment. However, the global shortage of donor tissue, risk of immune rejection, and variable long-term graft survival underscore the urgent need for alternative approaches, particularly in the setting of ocular surface diseases such as inflammation or dry eye that can compromise graft survival. Regenerative medicine has emerged as a transformative paradigm, offering strategies to restore corneal architecture and function through cell-based therapies, tissue engineering, and gene modulation. These strategies are promising, addressing structural repair and modulating wound-healing responses. In the corneal epithelium, cultivated limbal epithelial transplantation, simple limbal epithelial transplantation, and cultivated oral mucosal epithelial transplantation have expanded therapeutic options for limbal stem cell deficiency, with clinical trials demonstrating long-term ocular surface stability. Regulatory approval of commercial products, such as Holoclar and Nepic, confirms the potential of standardized regenerative products. Stromal regeneration with stromal and mesenchymal stem cells has shown promise in preclinical and early phase clinical trials, with intrastromal stem cell injection improving corneal transparency and biomechanics and potentially stabilizing progressive disorders such as keratoconus. For endothelial dysfunction, intracameral injection of cultured corneal endothelial cells supplemented with Rho-associated protein kinase (ROCK) inhibitors has yielded sustained corneal clarity and visual restoration at 5-10years, marking a paradigm shift from transplantation to minimally invasive, donor-independent therapies. Tissue engineering innovations, including matrices, hydrogels, and three-dimensional bioprinting, are advancing toward translation, while gene therapy approaches using viral vectors and Clustered Regularly Interspaced Short Palindromic Repeats -Cas9 are being explored to modulate angiogenesis, fibrosis, and inherited dystrophies. Overall, regenerative medicine is reshaping corneal therapeutics, offering effective alternatives to conventional transplantation with reduced donor dependence and improved safety. Future work must focus on long-term safety, cost-effectiveness, and equitable global access to realize its full clinical potential.

The increasing prevalence of night shift work (NSW) in our current professional landscape has raised significant public health concerns, particularly regarding its potential role in breast cancer (BC) development among women. Recognized by the International Agency for Research on Cancer (IARC) as a probable human carcinogen, NSW is believed to contribute to carcinogenesis primarily through circadian disruption induced by exposure to light at night. This review explores three key areas: (1) the biological mechanisms potentially linking NSW to BC, including melatonin suppression, oxidative stress, immune dysregulation, chronic inflammation, clock gene alterations, epigenetic modifications, telomere shortening, estrogen signaling disruption, vitamin D deficiency, and gut microbiome imbalance; (2) the emergence of novel putative biomarkers with might be relevant to early detection and precision risk analysis; and (3) the latest epidemiological evidence from case-control and cohort studies evaluating BC risk in female night shift workers, while considering the heterogeneity caused by exposure misclassification and other confounding factors. Altogether, these insights underscore the importance of integrating mechanistic, molecular, and epidemiological data, not only to deepen our understanding of the strength and nature of the relationship between NSW and BC, but also to support a precision medicine framework. This integrated approach is essential for improving individual risk stratification, guiding occupational health policies, and developing targeted preventive strategies for high-risk workers.

The management of infertility in women with bowel endometriosis remains a significant clinical challenge. The two primary therapeutic approaches include first-line medically assisted reproduction (MAR) and primary bowel surgery, with or without subsequent fertility treatments. While surgery can significantly improve fertility outcomes, the success of these interventions is influenced by several factors, and MAR may still be necessary for certain patients, especially those over 35 years or with complex disease patterns. In this narrative review, we assessed the outcomes of the main therapeutic strategies commonly offered to patients with bowel endometriosis-associated infertility and discussed the challenges inherent in evaluating reproductive outcomes in women with colorectal endometriosis.

Abstract Standardized outcome measures are essential for evidence-based pediatric audiology practice, yet Malaysia lacks unified national guidelines, risking inconsistent care quality and inequitable service delivery for children with hearing loss. This conceptual review presents a national perspective on pediatric audiology outcome measures, synthesizing findings from expert panel discussions, literature integration, and practice assessment through triangulation. Key insights were gathered through the Seventh Malaysian Audiology Scientific Conference forum, involving structured panels with government, private sector, and international representatives, plus insights from 180 forum participants. Current landscape analysis reveals public sector services follow established protocols with government investment in equipment upgrades, while private sector practices demonstrate significant variability. Critical gaps include sector variability, absence of unified standards, inadequate inter-facility comparison capabilities, and the need for tiered implementation approaches. Implementation challenges include fragmented service delivery, limited access to advanced tools outside specialized centers, workforce and infrastructure gaps, and private sector constraints. International examples, particularly the Welsh Primary Care Audiology Pathway, demonstrate successful integration models enhancing service consistency and equity. Strategic recommendations propose a three-phase framework: foundation (stakeholder coordination), development (culturally-adapted standards), and sustainability (monitoring and evaluation). A national task force comprising key stakeholders is recommended to lead standardization efforts, ensuring consistent, evidence-based care for children with hearing loss across Malaysia's diverse healthcare settings.

Who you gonna call? Understanding the shortages of the pediatric subspecialty workforce.

In the current energy transition landscape, characterised by the dual requirements of accelerated decarbonisation and increased resilience to disruptions in the electricity system, the concept of positive energy districts (PEDs) is becoming increasingly relevant [...]

The current healthcare landscape represents the vision to provide care closer to home in a more comprehensive way than ever before. However, with the existing workforce challenges within district nursing workforce and the shortfall in nurses, pressures on community-based services are expected to increase as they strive to meet this additional demand. The author explores contemporary issues related to recruitment and retention through the lens of existing government policy, which aims to address increasing caseloads, realignment of services, staff turnover and burnout and consider some of the potential solutions.

ABSTRACT Authenticity has emerged as a central theme in both academic discourse and business practice within the current virtual landscape. Nevertheless, prior marketing research has predominantly focused on the effect of authenticity on purchase decisions, largely overlooking “consumer decision‐making confidence”—a critical psychological variable essential for both short‐term revenue generation and the development of a long‐term sustainable ecosystem in the live‐streaming industry. To address this gap, this study employs an online survey methodology, recruiting participants via the Credamo and Wenjuanxing platforms (Study 1: N = 144, Study 2: N = 296), to investigate the influence of virtual streamer authenticity on consumer decision‐making confidence amid the rise of AI in live‐streaming commerce. The findings indicate that 3E assets significantly mediate this relationship. Furthermore, different interaction strategies are found to moderate this effect. Specifically, functional interaction strategies amplify the effect of authenticity on enhancing the “enabling‐the‐self” dimension, whereas social interaction strategies strengthen the authenticity effect on the “enticing‐the‐self” dimension. These findings advance influencer marketing research by thoroughly mapping the underlying process that drives decision‐making confidence and provide managers with actionable strategies for effective virtual streamer engagement.