Early Expansion Research Articles

Abstract 5177: Modeling 6q deletion and MYD88L265P-driven B-cell lymphomas in mice reveals early lymphomagenesis mechanisms and identifies the putative cell of origin

Abstract Chromosomal aberrations often represent early events in cancer development and might play a critical role in establishing malignant clones. Large chromosomal deletions typically involve the loss of multiple cooperating tumor suppressor genes, which makes it challenging to study their contribution to cancer pathogenesis. Recent genomic studies have identified the MYD88L265P mutation and chromosome 6q deletion as frequent alterations in Waldenstrom’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL). These genetic abnormalities are considered to be key drivers of oncogenic NF-κB signaling and are also observed in diffuse large B-cell lymphoma (DLBCL). Previous studies, including our own, have demonstrated that neither human MYD88L265P nor murine Myd88L252P mutations alone are sufficient to induce neoplastic transformation in mouse models. Chr6q deletion, containing multiple genes involved in B cell biology, might constitute a critical “second hit” necessary for sustaining MYD88L265P-induced signaling. This study aimed to elucidate the roles of MYD88L265P and Chr6q (syntenic to murine Chr10q) deletion in B-cell lymphoma pathogenesis. We generated the following genetically engineered mouse models: Myd88L252P/+;Cd19Cre/+, 10q+/-;Cd19Cre/+ and Myd88L252P/+;10q+/-;Cd19Cre/+. We have observed spontaneous development of low- and high-grade B cell lymphomas in aged cohorts of 10q+/-;Cd19Cre/+ and Myd88L252P/+;10q+/-;Cd19Cre/+ mice. Pathological analysis showed an expansion of lymphoplasmacytic B220- SOX5+ PAX5+ IgM+ B cells, which infiltrated the bone marrow, spleen and lymph nodes. To investigate the progression of B-cell changes during premalignant and malignant stages, we performed scRNA-seq on murine lymphoid organ samples. There was an early clonal expansion of B1 and memory B cells, potentially representing lymphoma precursor cells. Later on, these populations were replaced by larger cells frequently positive for Ki67, IRF4, and IgM, suggesting a transition from a low-grade WM-like disease to a high-grade DLBCL. Both early- and late-stage lymphomas exhibited elevated expression of therapeutic targets, including Bcl2, Ms4a1, Btk and Hck, offering potential avenues for intervention and therapy response studies. Additionally, profound alterations were observed in the T-cell compartment, with an increased frequency of PD1+ LAG3+ TIM3+ cells, suggesting immunotherapy targets that merit further validation. The mouse models provide valuable platforms for investigating the mechanistic roles of these genetic alterations and testing therapeutic strategies. In the future, we plan to validate the models as preclinical tools for studying MYD88 and Chr6q deletion-driven lymphomagenesis. This project was supported by the Robert A. Kyle Career Development Award from the IWMF and NIH grant R01CA273123. Citation Format: Filip Garbicz, Johany Penailillo, Senthilkumar Muthiah, Fernanda Cuevas, Tuyet Nguyen, Elisa Mandato, Eleonora Calabretta, Tomasz Sewastianik, Elena Ivanova, Aisha Saldanha, Moataz Noureddine, Rafael Irizarry, Margaret A. Shipp, Zachary Hunter, Steven P. Treon, Ruben D. Carrasco. Modeling 6q deletion and MYD88L265P-driven B-cell lymphomas in mice reveals early lymphomagenesis mechanisms and identifies the putative cell of origin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5177.

Chromosome-level genome assembly reveals adaptive evolution of the invasive Amazon sailfin catfish (Pterygoplichthys pardalis)

Catfish represents a diverse lineage with variable number of chromosomes and complex relationships with humans. Although certain species pose significant invasive threats to native fish populations, comprehensive genomic investigations into the evolutionary adaptations that contribute to their invasion success are lacking. To address this gap, our study presents a high-quality genome assembly of the Amazon sailfin catfish (Pterygoplichthys pardalis), a member of the armored catfish family, along with a comprehensive comparative genomic analysis. By utilizing conserved genomic regions across different catfish species, we reconstructed the 29 ancestral chromosomes of catfish, including two microchromosomes (28 and 29) that show different fusion and breakage patterns across species. Our analysis shows that the Amazon sailfin catfish genome is notably larger (1.58 Gb) with more than 40,000 coding genes. The genome expansion was linked to early repetitive sequence expansions and recent gene duplications. Several expanded genes are associated with immune functions, including antigen recognition domains like the Ig-v-set domain and the tandem expansion of the CD300 gene family. We also identified specific insertions in CNEs (conserved non-coding elements) near genes involved in cellular processes and neural development. Additionally, rapidly evolving and positively selected genes in the Amazon sailfin catfish genome were found to be associated with collagen formation. Moreover, we identified multiple positively selected codons in hoxb9, which may lead to functional alterations. These findings provide insights into molecular adaptations in an invasive catfish that may underlie its widespread invasion success.

Da’wah Strategies of the Prophet Muhammad (SAW) and His Companions: Lessons for Contemporary Muslim Preachers

The Da’wah (invitation to Islam) strategies of Prophet Muhammad (SAW) and his companions (Sahabah) offer profound insights into the effective propagation of Islam, combining wisdom, compassion, and adaptability to diverse contexts. Their method of inviting others to Islam was rooted in personal integrity, intellectual engagement, and social justice, offering timeless lessons for modern Islamic preachers. This paper examines the core Da’wah strategies employed by the Prophet and his companions, including the emphasis on knowledge, exemplary character, peaceful dialogue, and community engagement. It also explores how these strategies were integral to the early expansion of Islam, both within and beyond the Arabian Peninsula. Methodologically, this study utilizes a qualitative approach, conducting a textual analysis of Qur'anic verses and Hadith, alongside case studies of key companions such as Abu Bakr, Umar ibn al-Khattab, and Khalid ibn al-Walid. This analysis illuminates how their Da’wah efforts were influenced by the socio-political and cultural contexts of their time, providing a comprehensive understanding of their methods. By examining these methods, the paper provides key lessons for contemporary Muslim preachers, underscoring the significance of continuous learning, inclusivity, and the use of diverse communication platforms in Da’wah efforts. Additionally, it underscores the relevance of addressing contemporary issues, fostering unity within the Muslim community, and advocating for social justice. The study concludes that by integrating these foundational principles, contemporary Muslim preachers can effectively carry forward the legacy of Da’wah, adapting it to meet the needs of a rapidly evolving world while remaining deeply rooted in Islamic values.

Insulin-like growth factor 2 as a driving force for exponential expansion and differentiation of the neonatal thymus.

Like all organs, the thymus grows in size and function rapidly during development, but this growth comes to a halt after birth. However, the molecular mechanisms behind such a transition in the thymus remain obscure. Using single-cell RNA sequencing (scRNA-seq) of the murine thymic stroma, we identified that major transcriptomic changes occur in the endothelium and mesenchyme across the transition to homeostasis. Differentially expressed gene and intercellular network analyses of temporally resolved scRNA-seq data revealed fibroblast-derived insulin-like growth factor 2 (IGF2) as a candidate driving neonatal thymic expansion. We demonstrated that IGF2 activity promotes a cortical thymic epithelial cell-specific proliferation and is tightly regulated at the thymic growth transition. Bulk RNA-seq of human thymi across the transition also revealed that IGF2 drives thymic expansion, suggesting an evolutionarily conserved role. Our study highlights the role of fibroblast-derived IGF2 in promoting cortical thymic epithelial cell proliferation and differentiation, resulting in early thymic expansion that is followed by downregulation to establish homeostasis.

Anti-CTLA4 therapy leads to early expansion of a peripheral Th17 population and induction of Th1 cytokines.

The systemic immunological effects of combining anti-CTLA4 therapy with PD-(L)1 blockade remain incompletely characterized, despite the widespread use of this combination in treating various solid tumors across multiple stages of disease. Herein, we investigated the additive impact of anti-CTLA4 on peripheral immune signatures in patients undergoing PD-(L)1 blockade, using blood samples from a cohort of patients receiving checkpoint inhibitor therapy for advanced solid tumors. We performed in-parallel analysis of peripheral blood mononuclear cells (PBMC) using Cytometry by Time-of-Flight (CyTOF) and plasma cytokines using Luminex immunoassay. Our study cohort included 104 patients, 54 who received anti-PD(L)1 alone and 50 who received anti-PD(L)1 in combination with anti-CTLA4. As compared to single-agent anti-PD(L)1, combination therapy was associated with a greater expansion of CD4+ T helper cell subsets, including Th17 (adjusted p=0.04) and regulatory T cells (Treg) (adjusted p=0.02), after multivariable and multiple testing adjustment. In patients receiving anti-CTLA4, examination of functional marker expression within the Th17 subset revealed an increase in expression of the Th1-related transcription factor TBET (p=0.003). Assessment of the peripheral cytokine signatures showed an increase in Th1-associated cytokines (p=0.002) in recipients of combination anti-PD(L)1 and anti-CTLA4, particularly the IFN-inducible cytokines MIG (adjusted p=0.05) and IP-10 (adjusted p=0.05). Our results confirm prior reports that anti-CTLA4 therapy is associated with augmentation of Th17 cell subsets, and they also show that anti-CTLA4 may reshape CD4+ T-cell responses through Th17-to-Th1 plasticity, revealing a potential mechanism for enhanced antitumor immunity with broader implications immune modulation in immunotherapy.

An early functional adaptive NK cell signature drives optimal CD8 + T-cell activation and predicts sustained HIV-1 viral control.

Early expansion of adaptive NK cells during acute HIV-1 infection promotes long-term viral control.

Leukemogenic Kras mutation reprograms multipotent progenitors to facilitate its spread through the hematopoietic system.

Leukemia-driving mutations are thought to arise in hematopoietic stem cells (HSC), yet the natural history of their spread is poorly understood. We genetically induced mutations within endogenous murine HSC and traced them in unmanipulated animals. In contrast to mutations associated with clonal hematopoiesis (such as Tet2 deletion), the leukemogenic KrasG12D mutation dramatically accelerated HSC contribution to all hematopoietic lineages. The acceleration was mediated by KrasG12D-expressing multipotent progenitors (MPP) that lacked self-renewal but showed increased proliferation and aberrant transcriptome. The deletion of osteopontin, a secreted negative regulator of stem/progenitor cells, delayed the early expansion of mutant progenitors. KrasG12D-carrying cells showed increased CXCR4-driven motility in the bone marrow, and the blockade of CXCR4 reduced the expansion of MPP in vivo. Finally, therapeutic blockade of KRASG12D spared mutant HSC but reduced the expansion of mutant MPP and their mature progeny. Thus, transforming mutations facilitate their own spread from stem cells by reprogramming MPP, creating a preleukemic state via a two-component stem/progenitor circuit.

Development of an efficient differentiation culture system of murine HSC into megakaryocytes.

Development of an efficient differentiation culture system of murine HSC into megakaryocytes.

Non-commutativity in modified loop cosmology

In this study, we explore the pre-inflationary dynamics of the universe using a non-commutative extension of the mLQC-I framework. By incorporating a scalar field potential, we show that key features of Loop Quantum Cosmology (LQC), such as the quantum bounce and the super-inflationary phase, are preserved. Numerical solutions to the modified Hamiltonian equations, with initial conditions set at the quantum bounce, reveal that the universe’s early expansion rate is sensitive to the shape of the potential. For a chaotic potential, the inclusion of non-commutativity results in a faster expansion rate, whereas for the Starobinsky potential, the expansion rate decreases with increasing non-commutative parameter θ. Additionally, higher values of θ lead to an increased time derivative of the Hubble parameter, causing a shorter yet more expansive super-inflationary phase. Over time, Hubble parameters for different values of θ converge. For the Starobinsky potential, the Hubble parameter consistently decreases with larger θ, resulting in a prolonged super-inflationary stage. The study also addresses the validation of the Hamiltonian constraint during the evolutionary time.

Genomic Insights into Post-Domestication Expansion and Selection of Body Size in Ponies.

Horse domestication revolutionizes human civilization by transforming transportation, agriculture, and warfare patterns. Despite extensive studies on modern domestic horse origins, the intricate demographic history and genetic signatures underlying pony size remain unexplored. Here, a high-quality genome assembly of the Chinese Debao pony is presented, and 452 qualified individuals from 64 horse breeds worldwide are extensively analyzed. The authors' results reveal the conservation of ancient components in East Asian horses and close relationships between Asian horses and Western pony lineages. Genetic analyses suggest an Asian paternal origin for European pony breeds. These pony-sized horses share close genetic affinities, potentially attributed to their early expansion and adaptation to local environments. In addition, promising cis-regulatory elements influencing horse withers height by regulating genes such as RFLNA and FOXO1 are identified. Overall, this study provides insightful perspectives on the dispersal history and genetic determinants underlying body size in ponies, offering broader implications for horse population management and improvement.

Ultrafast expansion kinetics of femtosecond laser-induced optical breakdown in bulk fused silica

Abstract In this study, we employ femtosecond pump–probe transmission microscopy and complex Nomarski interferometry to investigate the ultrafast dynamics of laser-induced plasma and shock waves in bulk fused silica subjected to high laser intensities. It was found that the plasma channel, in its development, takes on a columnar shape with minimal variations during the early expansion stage between 130 and 200 ps. However, after 200 ps, the cylindrical shock wave commenced its departure from the plasma channel and gradually expanded outward along the radial direction. An electron density in the evolving plasma channel approached a level of ∼ 1.9 ∗ 10 20 cm − 3 , at a delay time of 50 ps. The resulting change in refractive index caused by electronic plasma was 0.05, while the reflectivity of the probe beam was ≈0.03 % . The blast wave model described the plasma and cylindrical shock wave expansion. A pressure of 65 GPa and a plasma temperature of a few eV were registered at a delay time of 150 ps. The resulting extreme conditions mapped to the cross-section analysis of the void and shock wave-affected area reveal polycrystalline structures near the periphery of the cavity at the geometrical focus. The areas more distant from the focus tend to show an amorphous character. These findings enrich the interpretation of femtosecond laser–dielectric interactions, with significant implications for micromachining, optical data storage, and the advancement of photonic device technologies.

Exploring the associations of gut microbiota with inflammatory and the early hematoma expansion in intracerebral hemorrhage: from change to potential therapeutic objectives.

Although a great deal of research has explored the possibility of a systemic inflammatory response and dysbiosis of the gut microbiota after an intracerebral hemorrhage (ICH), the relationships between gut microbiota and blood inflammatory indicators as well as their role in the hematoma expansion following an early-stage mild-to-moderate ICH (emICH) remain unknown. This study analyzes these changes and associations in order to predict and prevent hematoma expansion after emICH. The study included 100 participants, with 70 individuals diagnosed with emICH (30 with hematoma expansion and 40 without hematoma expansion, referred to as the HE and NE groups) and 30 healthy controls matched in terms of age and gender (HC). We used 16S rRNA gene sequencing to explore the gut microbial structure and its underlying associations with blood inflammatory parameters in the HE group. Our findings showed a significant decrease in the diversity and even distribution of microorganisms in the HE group when compared to the HC and NE groups. The composition of the gut microbiota experienced notable alterations in the emICH group, especially in HE. These changes included a rise in the number of gram-negative pro-inflammatory bacteria and a decline in the level of probiotics. Furthermore, we observed strong positive connections between bacteria enriched in the HE group and levels of systemic inflammation. Several microbial biomarkers (e.g. Escherichia_Shigella, Enterobacter, and Porphyromonas) were revealed in disparateiating HE from HC and NE. Analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) exposed disturbances in essential physiological pathways, especially those related to inflammation (such as the Toll-like receptor signaling pathway), in the HE group. Our exploration indicated that individuals with emICH, especially those with HE, demonstrate notably different host-microbe interactions when compared to healthy individuals. We deduced that emICH could rapidly trigger the dysbiosis of intestinal flora, and the disturbed microbiota could, in turn, exacerbate inflammatory response and increase the risk of hematoma expansion. Our comprehensive research revealed the potential of intestinal flora as a potent diagnostic tool, emphasizing its significance as a preventive target for HE.

Accounting for the expansion of the universe using an energy/momentum model to construct the space-time metric

Background The success of the theories of special and general relativity in describing localised phenomena, such as objects undergoing high speed motion or located in gravitational fields, needs no further elaboration. However, when applied to the evolution of the universe several problems arise which can require an additional model, e.g., inflation during the early expansion, and adjustments to parameters to account for phenomena such as the late-time acceleration of the universe. Methods Focusing on the difference between the ways in which space and time are measured, this paper shows that there are two paths which allow the equations of special relativity to be produced from the same basic postulates. Results Both the standard theory and the energy/momentum, or dynamic model, utilise the Minkowski metric, but with different coordinate systems. The dynamic model transforms Cartesian coordinates into an Euclidean form by multiplying the coordinates by functions of γ (= (1– ν 2/c 2)-1/2). When utilising these coordinates, the relativistic equations are unchanged for local phenomena such as the Lorentz coordinate transformation and the energy/momentum equation for high-velocity objects. Conclusions However, the derived coordinates alter the perceived overall structure of the universe in a manner that, for the simplest model under this system, allows the reproduction of observed cosmological features, such as the intrinsic flatness of the universe and the apparent late-time acceleration of its expansion, without the need of additional models or changes in parameter values.

Settlement discontinuity at Ak'awillay and the development of the Inca imperial capital region

Radiocarbon dates can offer important corollaries for historic events and processes, including territorial expansion and consolidation in early empires. Eighteen new radiocarbon dates from test excavations at Ak'awillay, near the Inca imperial capital of Cuzco, reveal new perspectives on interactions between the Incas and Xaquixaguana Valley groups. Rather than persisting as a regional centre, Ak'awillay declined well before early Inca expansion, remaining largely unoccupied until after an extensive empire had been established. This new chronology adds nuance to the growing understanding of local group interactions and how they contributed to Inca state development and imperial expansion.

Intrinsic p53 activation restricts gammaherpesvirus driven germinal center B cell expansion during latency establishment

Gammaherpesviruses are DNA tumor viruses that establish lifelong latent infections in lymphocytes. For viruses such as Epstein-Barr virus and murine gammaherpesvirus 68, this is accomplished through a viral gene-expression program that promotes cellular proliferation and differentiation, especially of germinal center B cells. Intrinsic host mechanisms that control virus-driven cellular expansion are incompletely defined. Using a small-animal model of gammaherpesvirus pathogenesis, we demonstrate in vivo that the tumor suppressor p53 is activated specifically in B cells latently infected by murine gammaherpesvirus 68. In the absence of p53, the early expansion of murine gammaherpesvirus 68 latency greatly increases, especially in germinal center B cells, a cell type whose proliferation is conversely restricted by p53. We identify the B cell-specific latency gene M2, a viral promoter of germinal center B cell differentiation, as a viral protein sufficient to elicit a p53-dependent anti-proliferative response caused by Src-family kinase activation. We further demonstrate that Epstein-Barr virus-encoded latent membrane protein 1 similarly triggers a p53 response in primary B cells. Our data highlight a model in which gammaherpesvirus latency gene-expression programs that promote B cell proliferation and differentiation to facilitate viral colonization of the host trigger aberrant cellular proliferation that is controlled by p53.

Assessment of the correlation between the volume of tongue, oral cavity, tongue/oral cavity volume ratio and the upper airway in unilateral cleft subjects: A CBCT study.

The current study was conducted to assess the volume of the tongue, oral cavity, and tongue/oral cavity and their correlation with the volume of the upper airway in cleft subjects compared with the control group. The study population included 60 CBCT images from dental school. The sample comprised 30 unilateral cleft patients and 30 sex and age-matched healthy subjects. The CBCT images were imported to the Mimics software in DICOM format. Then, the segmentation process was done in order to create distinct masks for the upper airway, oral cavity, and tongue. The software calculated the volume of the created masks. The volume of tongue, oral and upper airway were significantly lower in cleft patients than in the control group (P value < 0.05 taken as statistically significant). There was a weak but statistically significant correlation between the U.A.W.V and T.V in both cleft and non-cleft subjects. Additionally, there was a statistically significant correlation between the O.C.V and the U.A.W.V in cleft subjects. Except than the proportion of tongue/oral cavity volume, other volumetric measurements were significantly lower in cleft subjects than control group. This reveals that clefts are not necessarily more susceptible to obstructive sleep apnea. Also, the positive correlation between the volume of the tongue and oral cavity with the upper airway confirms that early expansion of the maxillary region in clefts helps significantly in increasing their upper airway volume.

Efficacy and safety of zanubrutinib combined with chimeric antigen receptor T-cell therapy targeting CD19 in refractory or relapsed diffuse large B cell lymphoma: A retrospective analysis.

Efficacy and safety of zanubrutinib combined with chimeric antigen receptor T-cell therapy targeting CD19 in refractory or relapsed diffuse large B cell lymphoma: A retrospective analysis.

Early expansion of TIGIT+PD1+ effector memory CD4 T cells via agonistic effect of alefacept in new-onset type 1 diabetes.

The CD2-depleting drug alefacept (LFA3-Ig) preserved beta cell function in new-onset type 1 diabetes (T1D) patients. The most promising biomarkers of response were late expansion of exhausted CD8 T cells and rare baseline inflammatory islet-reactive CD4 T cells, neither of which can be used to measure responses to drug in the weeks after treatment. Thus, we investigated whether early changes in T cell immunophenotypes could serve as biomarkers of drug activity. We characterized T cell responses by flow cytometry and identified an exhausted-like population of CD2low CD4 effector memory T cells coexpressing TIGIT and PD1 that expanded by 11 wk after the start of treatment. This population was not entirely spared from alefacept-mediated depletion in vivo or in vitro but recovered through homeostatic proliferation of CD2low cells in vivo. Proliferation of TIGIT+PD1+ effector memory CD4 T cells increased with treatment, with a concomitant reduction of proinflammatory cytokine production. The persistent increase of TIGIT+PD1+ effector memory CD4 T cells was specific to alefacept treatment; 2 other T cell depleting therapies, teplizumab and anti-thymocyte globulin, induced only a transient increase in this CD4 population. Our data suggest that the expanding TIGIT+PD1+ effector memory CD4 T cell population represents a promising biomarker of early treatment effects of alefacept. The nondepleting effects on proliferation and cytokine production also suggest agonistic activity by this CD2 targeted therapy.

Predictors and Outcomes of Hematoma Expansion and Neurological Decline in Intracerebral Hemorrhage: A Multisite Mobile Stroke Unit Study

BACKGROUND Hemorrhagic stroke, particularly intracerebral hemorrhage, is one of the leading causes of permanent disability worldwide. Early hematoma expansion (HE) is a key factor in neurological deterioration (ND) and functional outcomes post intracerebral hemorrhage. This observational cohort study examines the predictors and outcomes of HE and ND in spontaneous intracerebral hemorrhage patients using data from 3 Mobile Stroke Units (MSUs) in the United States. METHODS Patients diagnosed with spontaneous intracerebral hemorrhage within 4 hours of last known well were included. Data collection involved initial and follow‐up non‐contrast (computerized tomography) CT scans from MSUs and emergency departments, from which the rate of HE and ND were determined. The interrater reliability for radiographic signs of HE was also assessed. Predictive factors were analyzed using multiple logistic regression models. RESULTS Of the 55 patients who met the inclusion criteria, 27% experienced HE within the first 4 hours from last known well with the majority of HE occurring within the first 60 to120 minutes. Significant predictors of HE were a history of diabetes and blend sign on initial MSU CT scans. Predictors of ND included initial hematoma volume and the presence of hydrocephalus. Patients with HE and ND had a higher discharge modified‐Rankin Scale score and mortality rates. Interrater agreement on radiographic signs of HE varied, with moderate agreement on some signs and little to none on others. CONCLUSION Highest HE was seen within 60 to120 minutes from last known well for patients between MSU and emergency department transport. The blend sign and a history of diabetes emerged as key predictors of HE, whereas initial hematoma volume and hydrocephalus were significant for ND. Interventions to prevent HE and ND should be tested on the MSU in future studies.

Contralateral Coronal-Lambdoid Craniosynostosis Treated with Distraction Osteogenesis and Spring-Mediated Cranioplasty

Introduction: Treatment of multi-sutural craniosynostosis presents unique challenges and requires a patient specific approach. Patients with contralateral multi-suture craniosynostosis are particularly challenging as the surgical technique utilized must induce opposing forces of expansion. When patients present early in life, early dynamic expansion may be preferable to open approaches. Herein we report a 2-stage technique to treat contralateral right unicoronal and left lambdoid synostosis with simultaneous distraction osteogenesis and spring-mediated cranioplasty. Methods: A 3-month-old male presented to our clinic for concern for head asymmetry. A CT scan confirmed right coronal and left lambdoid craniosynostosis. Preoperative and postoperative head CT and 3D photogrammetry were used to compute the Head Shape Anomaly index (HSA) and difference in head volume from a personalized normative reference for shape and volume. Results: The surgery lasted 163 minutes, and the patient received a 168 mL blood transfusion. The patient was discharged after 3 days. Two springs were placed following a 1 cm strip craniectomy of the lambdoid suture, and a 40 mm uniplane cranial distractor was placed after a right fronto-orbital osteotomy. Devices were removed following activation and consolidation phases. There were no major complications. Postoperative 3D head CT showed correction of left lambdoid and right coronal craniosynostosis with improved plagiocephaly. The patient’s postoperative HSA Index improved from 4.39 pre-operatively to 2.85 at 145 days post-operatively. In addition, the difference in intracranial volume from the personalized normative reference improved from -87.35 mL pre-operatively to 1.65 mL post-operatively. Conclusion: This early dynamic expansion technique provided improved safety outcomes including decreased operative time, transfusion requirement, and hospital stay when compared to other techniques for multi-suture correction such as cranial vault reconstruction. This technique also produced desired results in shape correction and correction of volumetric anomalies. This illustrates the importance of innovation to develop patient specific surgical designs that maximize safety and morphologic outcomes.