Beyond its efficacy on atrial fibrillation, pulsed field ablation (PFA) presents potential advantages in ventricular arrhythmia. This study sought to investigate the feasibility of PFA for ventricular tachycardia (VT) and premature ventricular complexes (PVC). A systematic search (Scopus, PubMed, and Science Direct) with citation searching was performed on 9 January 2026. Studies evaluating the feasibility of PFA in VT and PVC were included. This study included seven studies (74 patients with VT and 86 with PVC). Pooled acute procedural success rate in VT was 0.92 (95% CI: 0.86-0.99) and in the PVC was 0.93 (95% CI: 0.86-1.00). During follow-up, VT recurrence rates ranged from 20% to 54%. PVC ablation demonstrated a significant burden reduction (MD: 86.54%; 95% CI: 59.21-113.86; p = 0.005) with long-term success rates ranging from 50% to 85%. Safety evaluation demonstrated satisfactory outcomes, with major adverse cardiovascular events (MACE) during follow-up occurring in four patients with high-risk comorbidity. Major adverse events (AEs) occurred in 11 patients and were preventable; minor AEs consisted solely of vascular access site AEs. PFA was feasible for VT and PVC ablation. Larger long-term studies and standardized protocol were urgently necessary to ensure efficacy with minimal AEs. www.crd.york.ac.uk/prospero identifier is CRD420251272352. Pulsed field ablation (PFA) is a newer technology for abnormal heart rhythms. It uses electrical pulses to treat parts of the heart tissue that cause abnormal rhythms. Unlike older treatments, it does not use heat or freezing. In the world, doctors are already used to treating atrial fibrillation. However, less is known about its use for ventricular arrhythmias. These include ventricular tachycardia and premature ventricular complexes. This study reviewed data from seven studies involving 158 patients. The study found that new technology worked well during the procedure in most patients. However, some patients later had the abnormal heart rhythm return, especially those with ventricular tachycardia. In patients with premature ventricular complexes, the treatment lowered the number of extra heartbeats. Serious complications were rare and mostly happened in patients who already had severe health problems. We found that most complications are also preventable by the doctors, although more research needs to be done in this area. Overall, PFA appears to be a promising and feasible technology for these types of heart rhythm disorders.
Modern military medical operations frequently occur in environments where access to specialized procedural care is limited by distance, mobility requirements, and constrained infrastructure. In these settings, forward medical teams must often manage complex conditions with limited personnel and equipment. Physician associates represent a critical component of the military medical workforce and frequently serve as a senior medical provider within forward and austere environments. Because physician associates are already embedded within deployed medical teams and are trained to perform a range of invasive procedures, expanding their role in image-guided procedural care represents a potential pathway to strengthen forward medical capability without increasing personnel requirements. This article examines the potential role of physician associates as procedural extenders for image-guided care in expeditionary medical systems. Military medical literature, radiology workforce analyses, and global interventional radiology education initiatives were reviewed to evaluate how physician associates could safely perform selected image-guided procedures with appropriate training and oversight. Historical experience demonstrates that physician associates have long served as procedural leaders in deployed settings, routinely performing vascular access, thoracic drainage, and other invasive interventions within Role 1 and Role 2 medical elements. Civilian data further show that advanced practice providers safely perform procedures such as paracentesis, thoracentesis, venous access, drain placement, and lumbar puncture with outcomes comparable to physicians when structured training and supervision are present. These precedents suggest that physician associates may be well positioned to expand their scope to include selected image-guided procedures when supported by focused education and standardized credentialing. A training model emphasizing ultrasound proficiency, procedural decision-making, and complication management could enable physician associates to perform procedures such as vascular access, fluid drainage, and diagnostic aspiration in austere environments. Simulation-based training and tele-supervision networks may further support safe implementation while maintaining oversight from physician specialists. Positioning physician associates as procedural extenders aligns with broader military medical priorities that emphasize modular, capability-based care and efficient use of existing personnel. By leveraging an already deployed workforce, this model could expand access to minimally invasive procedures in combat, humanitarian, and prolonged casualty care environments while maintaining continuity with higher-echelon medical facilities. Prospective evaluation will be necessary to fully define appropriate procedural scope, training standards, and safety outcomes.
Primary care is becoming increasingly complex, with primary care physicians (PCPs) facing rising workloads driven by workforce shortages, growing administrative demands, and expanding clinical responsibilities. Recent advances in large language models (LLMs) offer new opportunities to support PCPs across clinical, administrative, and communication-related tasks within their workflows. Understanding how these technologies are perceived and used in primary care practice is, therefore, critical to inform their safe, effective, and human-centered implementation. This study aimed to explore Dutch and US PCPs' perceptions and experiences regarding the use of LLMs in clinical practice, with particular attention to clinical usability, communication and teamwork, and implications for everyday workflows. We conducted a qualitative study using semistructured interviews with 15 PCPs from the United States and the Netherlands. Data were collected between February and June 2025 and analyzed using reflexive inductive thematic analysis. Ten themes emerged related to the use of LLMs in primary care clinical practice, each theme consisting of a set of subthemes. We found that LLMs are being integrated into primary care as both clinical and communication support tools, assisting with diagnostic reasoning, administrative tasks, workload management, and interprofessional and patient communication. While PCPs reported perceived benefits, they also expressed concerns related to safety, efficiency, authenticity, and the preservation of the therapeutic relationship, highlighting the need for careful and context-sensitive use. Our findings suggest that LLMs are already being integrated into primary care in diverse ways, with their value shaped by both contextual factors and clinician judgment. Understanding how clinicians navigate LLM use in everyday practice is essential to ensuring that LLMs support high-quality, patient-centered primary care and inform organizational policy and LLM design.
Prostate cancer survivorship is becoming an increasingly important issue in Tanzania, especially because follow-up care is still heavily centralised in a few specialised centres. This model is difficult to sustain in a country with a limited number of oncologists and specialised facilities. At the same time, there is growing recognition both globally and locally that primary healthcare (PHC) should play a major role in supporting cancer survivors. With this in mind, the present study set out to determine the proportion of prostate cancer survivors who actually use PHC services after completing active treatment, and to identify the factors that influence this pattern of care. A cross-sectional study was conducted at Besta Super Specialised Polyclinic in Dar es Salaam, recruiting 213 survivors who completed radiotherapy between January 2021 and December 2023. Data were collected via medical record reviews and telephone interviews using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer Module to assess symptom burden. The study found that 69.0% of survivors utilised PHC services, primarily at district hospitals (82.3%). Rural residence was the strongest predictor, with rural survivors over ten times more likely to access care than their urban counterparts. Higher education, early-stage diagnosis and severe treatment or sexual side effects also significantly increased utilisation. Interestingly, mild urinary symptoms were associated with higher PHC use compared to severe cases. These results suggest that a significant proportion of prostate cancer survivors in Tanzania are already engaged with PHC as a source for addressing survivorship issues, particularly those in rural settings with high symptom burdens. Given the persistent gaps and challenges in accessing specialised cancer services, it becomes even more important to recognise, understand and strengthen the role of PHC facilities as an essential part of the country's cancer care system.
The phase 3 NIMBLE trial demonstrated the efficacy of cemdisiran, an siRNA inhibitor of hepatic C5 synthesis, in patients with myasthenia gravis, making it the first complement inhibitor in the disease to employ this novel mechanism of action. These results expand the growing therapeutic landscape that already includes three FDA-approved complement inhibitors for myasthenia gravis.
High-impact sports participation may exacerbate pelvic floor dysfunctions (PFDs), a condition already common among women, in the female athletic population. In this population, pelvic floor health knowledge (PFHK) is key to preventing dysfunctions and sustaining performance. It was hypothesized that PFHK and dysfunctions in female athletes would differ according to age, education level, marital status, sport type, years of sports participation, and physical activity level. A total of 127 female athletes aged 16-40 years were recruited from various sports disciplines. Pelvic floor health knowledge (Pelvic Floor Health Knowledge Quiz), pelvic floor dysfunctions (Pelvic Floor Distress Inventory-20, PFDI-20), and physical activity levels (International Physical Activity Questionnaire-Short Form) were measured. The Mann-Whitney U test and Spearman correlation were used for statistical analysis. The mean age of participants was 21.1 ± 5.3 years, with 10.2 ± 5.3 years of sports participation. While 91.3% correctly identified the pelvic floor location, awareness of pelvic floor muscle training was limited. Athletes > 20 years and those with bachelor's or postgraduate education had significantly higher pelvic floor health knowledge (p < 0.05). Sports participation (> 10 years) was associated with higher risk/etiology and total scores (p < 0.05). PFDI-20 scores showed no significant correlations with demographic or sport-related variables (p > 0.05). While female athletes identify the pelvic floor's location, their knowledge of its function and treatment remains limited; therefore, integrating targeted education into athletic programs is essential to mitigate dysfunction risks and optimize long-term performance.
Sepsis is a highly heterogeneous syndrome, and conventional clinical indicators and single biomarkers often fail to capture its biological complexity or support precise risk stratification. To clarify the development of research in this area, this bibliometric study analyzed the literature on the clinical translation of genetic variation and multiomics biomarkers in sepsis. Publications were retrieved from PubMed, Web of Science Core Collection, and Scopus for the period from 2004 to 2025, and 940 eligible records were analyzed using Bibliometrix, VOSviewer, and CiteSpace. The results showed rapid expansion of the field, with annual output increasing from 1 publication in 2004 to 185 in 2025. China and the United States emerged as the leading contributors, while major institutions and journals reflected strong interdisciplinary collaboration across critical care, molecular biology, and translational medicine. The knowledge structure of the field has evolved from early emphasis on polymorphisms, susceptibility, and conventional inflammatory biomarkers toward metabolomics, transcriptomics, genomics, precision medicine, machine learning, and Mendelian randomization. At the same time, clinically relevant themes such as mortality, septic shock, acute kidney injury, and neonatal sepsis have remained central. These findings map a research trajectory from exploratory biomarker discovery toward translational frameworks for sepsis endotyping, prognostic evaluation, and risk stratification, but they should not be interpreted as evidence that the identified biomarkers or models are already clinically implemented. Future progress will depend on multicenter prospective validation, standardized analytic pipelines, broader population representation, and clinically deployable models that can translate molecular heterogeneity into real-world decision-making.
To develop and internally evaluate an age-assisted dual-input model for bone age assessment in late adolescence using paired hand-wrist and knee radiographs. This single-center retrospective study included 547 adolescents aged 13-19 years with paired left hand-wrist and left knee radiographs (1094 images) acquired during routine clinical care. Data were split at the subject level into training, validation, and internal held-out test sets (70%/10%/20%; 382/55/110 subjects), keeping paired images from each subject in the same subset. A ShuffleNet v2-based model used hand and knee radiographs as visual inputs and incorporated chronological age and sex as auxiliary variables. The validation set was used for model selection, and final performance was evaluated on the internal held-out test set using mean absolute error, root mean square error, and intraclass correlation coefficient. The final model achieved a mean absolute error of 3.77 months, root mean square error of 4.58 months, and intraclass correlation coefficient of 0.984, with 98.18% of predictions within 12 months of the reference standard. Internal ablation comparisons showed lower errors with paired hand-knee inputs and demographic variables than with single-site inputs. In this single-center retrospective cohort, the age-assisted dual-input framework showed promising internal performance for late-adolescent bone age assessment. Independent multicenter external validation is required before clinical deployment, forensic/disputed-age use, or legal decision-making. Knee radiographs should be used only when already available or medically justified, not as routine additional imaging.
Decisions regarding driving licence eligibility represents a complex medical and legal challenge, requiring careful consideration of both public safety and individual interests. The present paper provides a brief overview of the legal and administrative framework of fitness-to-drive evaluation, the roles of the professionals involved in the process, and key issues related to cognitive assessment. While physical symptoms associated with neurological conditions are generally objectively identifiable, cognitive impairments often remain less apparent and may significantly affect driving ability even in milder forms. The diagnostic accuracy of currently used neuropsychological tests is moderate, which limits the reliability of clinical decision-making. In this context, we present a prospective study conducted in stroke patients, in which a validated model based on the combination of multiple neuropsychological tests and logistic regression was developed. The model explicitly accounts for uncertainty and does not enforce categorical decisions in all cases, thereby allowing clinicians to refrain from definitive judgement in borderline cases. Although the method was validated in a stroke population, the proposed approach may be extended in future research to larger populations, such as older drivers. This would require the selection and validation of age-specific cognitive tests, which may support decision-making already at the level of primary care. Orv Hetil. 2026; 167(28): 1097-1104. A gépjárművezetésre való alkalmasság megítélése komplex orvosi és jogi feladat, amelynek során a közlekedésbiztonsági és az egyéni szempontok egyaránt mérlegelendők. A jelen közlemény rövid áttekintést nyújt a gépjárművezetői alkalmasság megítélésének jogi és közigazgatási hátteréről, az eljárásban részt vevő szereplők feladatairól, továbbá a kognitív alkalmasság kérdéseiről. Míg a neurológiai betegségekhez társuló fizikális tünetek általában objektíven megítélhetők, a kognitív működészavarok gyakran rejtve maradnak, és már enyhébb formájukban is jelentősen befolyásolhatják a vezetési képességeket. A jelenleg önmagukban alkalmazott neuropszichológiai tesztek diagnosztikus pontossága mérsékelt, ami korlátozza a megbízható döntéshozatalt. Ezzel összefüggésben ismertetünk egy stroke-betegek körében végzett prospektív vizsgálatot, amelyben több neuropszichológiai teszt kombinációjára épülő, logisztikus regresszión alapuló, validált modellt alakítottak ki. A modell a szakterületen megjelenő bizonytalanságot explicit módon kezeli, nem törekszik minden esetben kategorikus döntésre, így lehetőséget biztosít a klinikus számára a döntéshozataltól való tartózkodásra a határértéken teljesítő betegek körében. A módszert stroke-betegek körében validálták, ugyanakkor az ismertetett megközelítést jövőbeli kutatások olyan, nagyobb létszámú csoportokra is kiterjeszthetik, mint az időskorú gépjárművezetők. Ennek érdekében korcsoport-specifikus módon kiválasztott és validált kognitív tesztek használata javasolt, amelyek már az alapellátás szintjén támogathatják a döntéshozatalt. Orv Hetil. 2026; 167(28): 1097–1104.
Mast cells (MCs), as innate immune cells residing in cutaneous tissues, serve as critical mediators in the cross-talk between the neuroendocrine and immune systems. Upon activation by internal or external stimuli, MCs synthesize, accumulate, and secrete a variety of regulatory mediators, thereby exerting multifaceted effects through their secretory capacity and regulatory functions. Vitiligo, a complex disorder with a heterogeneous etiology encompassing genetic susceptibility, oxidative stress, autoimmunity, and neurogenic components, remains incompletely understood. Current pathogenetic models based solely on neural, humoral, or immunological frameworks fail to provide a comprehensive explanation for its development. Despite the incomplete characterization of mechanisms driving MC accumulation in vitiligo lesions, therapeutic agents targeting MCs and their signaling pathways (e.g., ketotifen, imatinib) have already been clinically implemented. Notably, MCs exhibit bidirectional interactions with neural and endocrine systems: they respond to neurotransmitter and hormonal signals while simultaneously releasing bioactive substances that reciprocally modulate neural activity, endocrine balance, and local immune responses, ultimately impacting melanocyte function. Consequently, targeting MCs and their key signaling pathways(e.g., the MrgX2-PAR2 axis and chymase-TLR4 pathway) represents a promising novel approach for vitiligo management, with potential applications in controlling disease progression, preventing relapse, and advancing therapeutic development.
Vision depends on the continuous recycling of the visual pigment chromophore 11-cis-retinal, which is converted by light into all-trans-retinal at the onset of the phototransduction cascade. Cellular retinaldehyde-binding protein 1 (CRALBP1) is a key component of both the canonical visual cycle in the retinal pigment epithelium (RPE) and the cone-specific recycling pathway mediated by Müller glia (MG) cells. Previous studies demonstrated that knockout of the RPE-specific gene rlbp1a (encoding CRALBP1) results in severe physiological and morphological defects that are evident already at cone dominant larval stages in zebrafish. In contrast, mutants lacking the MG-specific paralog rlbp1b showed no obvious phenotype during early development. Here, we show that juvenile rlbp1b mutants, when the retina has incorporated rod photoreceptors, exhibit reduced b-wave amplitudes in the electroretinogram under dark-adapted conditions, accompanied by a progressively prolonged time-to-peak at higher light intensities. These results underscore the importance of both illumination conditions and retinal maturation when investigating visual pigment recycling dynamics in cone vision.
Pemphigus vulgaris is a potentially life-threatening autoimmune blistering disease for which corticosteroid minimization can be difficult when prior steroid toxicity has already occurred. We report a 60-year-old woman with severe mucocutaneous pemphigus vulgaris confirmed by clinical, immunopathologic, and serologic findings, who had previously developed femoral head avascular necrosis during high-dose prednisone therapy and also had advanced chronic kidney disease, hypoalbuminemia, and anemia. Rituximab was discussed as a guideline-supported first-line option; however, after counseling regarding its expected benefits and potential adverse effects, the patient declined rituximab. Therefore, dupilumab was introduced off-label as an adjunctive corticosteroid-minimizing approach together with oral prednisone 30 mg/day and supportive care. The Pemphigus Disease Area Index was 111 during the first treatment week and decreased to 22 by week 6, when disease control was achieved with cessation of new lesions and marked healing of pre-existing erosions. Prednisone was then tapered gradually. Complete re-epithelialization was achieved by approximately month 4 while the patient was receiving oral prednisone 7.5 mg/day, and clinical stability was maintained through month 6 after dupilumab discontinuation at month 4. No adverse events were observed. This case supports the clinical feasibility of dupilumab-assisted corticosteroid minimization in selected patients with pemphigus vulgaris and major treatment-related constraints, while further evidence is needed regarding patient selection, duration of therapy, and long-term relapse risk.
ObjectiveTo examine longitudinal changes in depressive symptoms during a 30-session course of repetitive transcranial magnetic stimulation (rTMS) in routine clinical practice, with particular attention to symptom change by mid-treatment.MethodsIn this single-center, naturalistic, retrospective observational study, 24 patients with unipolar depressive disorder diagnosed in routine clinical practice according to the International Classification of Diseases, 10th or 11th revision, were included. The primary outcome was change in 17-item Hamilton Depression Rating Scale (HAMD-17) total score at baseline, after 15 sessions, and after 30 sessions, analyzed using a linear mixed-effects model. Secondary analyses examined the 6-item Hamilton Depression Rating Scale (HAMD-6) and the insomnia 3-item score.ResultsHAMD-17 total scores decreased significantly over time. Estimated reductions from baseline were 8.58 points at mid-treatment and 12.99 points at end-of-treatment, corresponding to reductions of 37.9% and 57.4%, respectively. A further 4.41-point reduction was observed from mid-treatment to end-of-treatment. HAMD-6 also decreased significantly across treatment, whereas the insomnia 3-item score improved mainly between baseline and mid-treatment.ConclusionsIn this small real-world cohort, depressive symptom scores decreased during rTMS, with substantial reduction already evident by 15 sessions. Mid-treatment assessment may provide clinically useful information during treatment, although these findings should be interpreted as hypothesis-generating.
The preservation of samples, whether they are from humans, cell lines, animals, plants, or other resources, usually follows a similar process. They are packaged in appropriate containers, whether tubes for cryogenic containers or boxes in freezers or other systems. For this biological sample database to be and remain useful, the samples must be appropriately cataloged and consecutively maintained in a document. After all, only when it is clear where which sample is located, the biological database has a value. In many cases this documentation is done in local spreadsheets and saved in e.g. CSV or XLSX format. In some cases, there are even handwritten records to comprehend where which sample is located. The intention behind a biological database is mainly the collection of rare material, but also the withdrawal of this material from the storage for further analysis, partly in-house but presumably also with external cooperation partners. If a sample is now taken from a container that has already been completely filled and stored, this empty space can only be re-allocated with a sample with great administrative effort, since new samples would otherwise be stored in the container that is currently active. With NORG we address this problem. NORG offers a stand-alone software solution via webservices to catalog e.g. nitrogen tanks and store the contents digitally with a color-coding for the filling level of the storages. In addition, NORG can trace who sent which sample to whom and when, for example to have it analyzed by a cooperation partner.
Process engineering often requires continuous monitoring of structural health in components exposed to chemically aggressive environments or high temperatures. Examples include thermal solar power plants, where liquid-metal heat-transfer fluids must be monitored to ensure safe and efficient operation, and lithium or next-generation batteries, where liquid-metal electrodes or electrolytes may develop uneven flow, instabilities, or hotspots detectable in real time using ultrasound. Conventional contact ultrasound imaging, however, is limited in these applications because transducers are highly sensitive to harsh conditions, since harsh environment already include elevated temperatures, often resulting in device failure. Waveguides provide a promising alternative by shielding transducers from aggressive environments. Single-mode waveguides (SMWGs) have been widely studied for ultrasound testing, offering protection from thermal damage but requiring slow point-by-point scanning for imaging. Multimode waveguides (MMWGs) have therefore been proposed for ultrasound imaging at high temperatures, though challenges remain regarding wettability, geometry, boundary conditions and the development of aberration correction algorithms to address wavefront distortion. This paper presents a systematic review of ultrasound waveguide transducers for structural health monitoring under high-temperature conditions. It evaluates key designs, highlighting their benefits, drawbacks and contributions to knowledge and surveys aberration correction methods and modelling approaches applicable in harsh environments. The review also traces the evolution from SMWGs to advanced MMWGs that exploit multiple wave modes, discusses opportunities in computational ultrasound imaging, and outlines future research directions. These findings support the optimization of waveguide-based ultrasound imaging for high-temperature liquids in solar power and battery applications, with potential transferability to improve medical ultrasound imaging through aberrative medium (e.g skull).
Digital focus groups are increasingly used in health research, yet their methodological implications within complex interventions remain insufficiently examined. When conducted with pre-existing cohorts, digital focus groups may function not only as evaluative tools but also as relational and socio-technical encounters that shape the generation of qualitative data. The goal of the present study was to examine how digital focus groups operate within this context. This study presents a methodological re-analysis of focus group material originally collected for the evaluation of a hybrid psychosocial prevention intervention, examining how digital focus groups operate within this context following the perspective of Situational Analysis. Digital focus groups were conducted with participants who had completed the hybrid intervention together in fixed cohort groups, meaning participants were already acquainted with one another prior to the focus group sessions. For the analysis, the transcripts were examined using descriptive, inductive coding. Verbatim quotations were used as methodological markers to illustrate how relational, emotional and technological factors shaped the data. Pre-existing cohort cohesion strongly influenced how participants engaged in the digital setting, fostering emotional safety, peer-supported learning, motivational reinforcement and opportunities for self-regulation. Digital platforms structured visibility, turn-taking and synchronization, while differences in devices, connectivity and digital literacy affected participation and the stability of group interaction. The researcher role expanded to include facilitation, technical troubleshooting and emotional anchoring, making the research team part of the socio-technical infrastructure. At times, the focus groups elicited supportive or motivational effects that echoed elements of the intervention itself, blurring the line between evaluation and unintended interventional effects. Focus groups in intervention research operate as relational encounters rather than neutral data-collection tools. This applies particularly to Digital Focus Groups. Recognizing how pre-existing relationships, technological environments and researcher involvement shape interaction is essential for methodological transparency and rigorous interpretation. The findings highlight the importance of reflexivity, attention to digital differences, and awareness of unintended interventional dynamics when designing and interpreting digitally mediated qualitative methods in healthcare contexts. Furthermore, the findings indicate that the choice between digital and in-person FGs should not be guided by pragmatic considerations alone, but by the relational, technological and institutional conditions of the research situation. DRKS-ID: DRKS00033080 (registration date: December 7, 2023).
Transitional care after a hospital stay remains a challenge in Germany. Despite the legal obligation for structured discharge management that has been in place since 2017, seamless transition to post-acute care is still not consistently available. This scoping review aims to compile available studies on discharge management in Germany, identify key challenges for patients and stakeholders, and present measures that have already been implemented. This scoping review followed the methodology of the Joanna Briggs Institute and the PRISMA-ScR guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). A systematic search was conducted in four bibliographic databases (CareLit, Cochrane Library, MEDLINE via PubMed, Web of Science Core Collection), supplemented by reference screening and hand searching. Using predefined criteria, German-and English-language primary and secondary studies, as well as gray literature from 2015 onwards, were included, focusing on hospitalized patients in Germany and those involved in discharge management. Thirty studies were included. Interventional studies demonstrated limited effectiveness, particularly in preventing hospital readmissions. Non-interventional research identified barriers such as inconsistent implementation, absence of standardized procedures, shortages of resources, and poor communication between care sectors. Structured assessments, standardized discharge summaries, and case managers showed potential to strengthen the continuity of care and improve patient outcomes. Cross-sectoral care in Germany requires stronger interprofessional collaboration, binding standards, and flexible models adaptable to local conditions. Despite useful insights, further research is urgently needed to evaluate, implement, and compare existing strategies and pilot programs.
In March 2026, a two-days' international workshop entitled "Hox- and TALE transcription factors: From developmental regulatory networks to disease states" took place in the historical guest house of the University of Heidelberg. The workshop recalled previous workshops organized under the European COST action between 2008 and 2013 and explored new advances in Hox/TALE biology in the context of congenital conditions. Hox- and TALE-homeodomain (HD) family proteins are highly conserved developmental transcription factors (TFs) that were originally characterized as major instructors providing spatial-temporal coordinates along the antero-posterior axis in bilaterian embryos. Hox and TALE proteins are also known to play numerous additional functions during embryogenesis, as well as during the adult life. Not surprisingly, several diseases and congenital malformations result from the aberrant expression or function of Hox- and/or TALE-encoding genes in human. Disorders that are attributable to already known mutations in Hox- and TALE-genes are expected to manifest themselves overtly. However, other mutations or allelic variants affecting Hox- and TALE-genes, or genes that encode for proteins they associate with, may produce more subtle effects. A central question of the workshop was therefore to explore whether the existence of such mutations or variants can be predicted based on research findings in model organisms. Against this backdrop, the workshop revealed novel functional and molecular aspects of Hox and TALE in the context of different animal model systems and regulatory pathways (Figure 1). It also illustrated the power of most recent technologies associated with dedicated bioinformatics tools in deciphering Hox/TALE molecular complexity at an unprecedented level in vivo. Time was dedicated for stimulating discussions and the workshop was also a good opportunity to bring together seniors and more junior colleagues in the Hox/TALE field. Over these two days, the Hox/TALE community not only demonstrated its remarkable dynamism but also raised key questions that are sure to inspire exciting research for years to come.
The exponential growth of biomedical literature creates a cognitive bottleneck in drug target discovery, particularly for identifying therapeutically relevant mechanisms beyond established pathways. In ocular neovascularization, anti-VEGF therapies are standard of care, yet non-response and resistance remain critical unmet needs. We present an integrated computational framework combining Graph Retrieval-Augmented Generation (GraphRAG)-based literature mining, pathway co-localization analysis, and deep learning-based druggability assessment for systematic target prioritization. Using 5562 angiogenesis-related PubMed abstracts, we constructed a vascular knowledge graph (17 842 nodes; 9555 edges) and applied pathway co-localization with vascular endothelial growth factor A (VEGF-A) as a biological filter. As a validation step, the workflow recovered four targets-fibroblast growth factor 2, transforming growth factor-beta 1, interleukin-1 beta, and matrix metalloproteinase-9-already supported by clinical or advanced preclinical development, demonstrating concordance with expert-driven selection. Iterative querying subsequently identified two additional mechanistically supported candidates, fibroblast growth factor 1 and hepatocyte growth factor, sharing receptor tyrosine kinase-centered pathways with VEGF-A but lacking clinical evaluation in ocular neovascularization. Deep learning-based structural analysis (DeepSite and PocketMiner) identified high-confidence ligandable pockets for all six candidates. This work demonstrates how GraphRAG can systematically mine existing literature to recover known targets and surface literature-supported candidates that may be underprioritized for translational development. Rather than claiming de novo discovery, we emphasize the framework's utility as a scalable, transparent, and reproducible methodology for overcoming citation bias and literature overload. The workflow is generalizable to other complex, literature-rich disease domains.
Rapidly decreasing costs of sequencing whole genomes has caused a boom in genomic resources for many species. However, many key nonmodel systems that were sequenced early in the genomic revolution lack assemblies that reflect the quality and contiguity that are routine with current technology. Some of these "early for assembly, late for contiguity" genomes belong to the butterfly genus Heliconius, a remarkably fruitful clade for exploring questions of phenotypic mimicry, speciation dynamics, and population genetics. We de novo assembled five new reference genomes of Heliconius butterflies based on PacBio HiFi sequencing: two subspecies of H. erato, two subspecies of H. melpomene, and a closely related species, H. numata. While independent assemblies of multiple subspecies are already a valuable resource, these specific genomes are important for exploration of the genomic basis of mimicry, because the four H. erato and H. melpomene genomes represent two pairs of H. erato/H. melpomene local comimics. These genomes prove to be high quality (merqury quality score 51-58) and approach completeness (>98% BUSCO complete genes) over a lower number of longer contigs than earlier Heliconius genomes, illustrating how PacBio long-read technology alone can unlock untapped genomic resources. This set of high-quality, uniformly processed genomes represents an important resource for exploring the genomics of adaptation, hybridization, and speciation. Although a Heliconius butterfly was among the first animal genomes to be sequenced, the genus lacks high-quality, publicly accessible, de novo reference genomes for most of its species. This is particularly important for Heliconius because independent and complete genomes are necessary to unambiguously determine the history of introgression and phenotypic innovation that makes this system so relevant for evolutionary research. We address this gap by generating deep-coverage PacBio long-read data from 5 Heliconius subspecies, assembling genomes de novo with a uniform and reproducible Snakemake processing pipeline. We recover excellent genome contiguity, quality, and completeness scores using only long-read data. We further annotate these genomes with subspecies-specific RNA-seq data to produce annotations with >97% BUSCO completeness. This group of Heliconius genomes represent an important contribution of identically processed, high-quality genomes for comparative genomic investigation into the evolution and innovation of ecologically relevant phenotypes.