United States

### Background
Type 1 diabetes (T1D) is characterized by autoimmune-mediated destruction of pancreatic β cells, leading to progressive loss of β-cell function and insulin deficiency. Crosstalk between the immune system and β-cell signaling contributes to disease progression, highlighting inflammatory pathways as potential therapeutic targets. While the development of an anti-CD3 monoclonal antibody against autoreactive T cells represents a significant advance in delaying the onset of insulin dependence, new approaches are needed to delay β-cell destruction in patients with diabetes-related autoantibodies. Our lab previously showed that ATI-450, a selective p38α/MK2 inhibitor, and AZD8931, an EGFR/ERBB2/ERBB3 inhibitor, delay the onset and reduce the incidence of T1D in female nonobese diabetic (NOD) mice. To explore the mechanism(s) by which ATI-450 and AZD8931 attenuate T1D, we examined whether these inhibitors could mitigate cytokine-induced β-cell dysfunction by modulating the expression of senescence-related markers and β-cell identity/function genes. 

### Methods
MIN6 cells were co-treated for 24 hours with cytokines (IL-1β, TNF-α, IFN-γ; 2.5 ng/mL each) ± ATI-450 (2µM) or AZD8931 (5 µM). DMSO was used as a control. Total RNA was extracted and reverse-transcribed into cDNA using standard kits. Quantitative real-time PCR was performed using synthesized cDNA and primers obtained from PrimerBank. Samples were run in triplicate, and relative mRNA expression was determined by the ΔΔCt method, normalized to mouse TATA-binding protein levels.

### Results
Cytokine-stress increased the relative expression of the senescence-related marker p21cip1 by 2.5-fold compared to DMSO control. Co-treatment with either ATI-450 or AZD8931 attenuated this cytokine-induced upregulation, suggesting that these inhibitors may delay the onset of senescence by blocking pro-inflammatory signaling pathways. Cytokine-stress reduced the relative expression of the β-cell identity/function genes Ucn3 and MafA by ~2.0-fold and ~1.5-fold, respectively, compared to DMSO control. Co-treatment with either ATI-450 or AZD8931 attenuated the cytokine-induced downregulation of Ucn3 and MafA, indicating that these compounds may help preserve β-cell functional identity.

### Conclusion
These findings suggest that both ATI-450 and AZD8931 can protect MIN6 cells from cytokine-induced dysfunction in vitro by reducing expression of the senescence-related marker p21cip1 and preserving key β-cell identity/function genes such as Ucn3 and MafA. This provides mechanistic insights for the in vivo effects of these inhibitors to reduce T1D incidence in NOD mice, revealing specific inflammatory pathways in β-cells that might be targeted for β-cell preservation. Since both inhibitors demonstrated favorable safety profiles in clinical trials for other diseases, these compounds could be investigated for preventing T1D in islet autoantibody-positive individuals.

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ATI-450 and AZD8931 Protect MIN6 Cells from Cytokine-Induced Dysfunction

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technical paper

### Background
Retinopathy of prematurity (ROP), a leading cause of childhood blindness, involves abnormal vascular proliferation and retinal detachment. Known risk factors include supplemental oxygen exposure, low gestational age (GA), and low birth weights (BW). Emerging evidence suggests early-life gut dysbiosis may contribute to ROP progression via the gut-retina axis and subsequent inflammatory pathways. Our group previously identified distinct gut microbial profiles in infants with severe ROP compared to those without. Systemic antibiotics are major disruptors of the gut microbiome, yet few studies have explored antibiotic exposure as a risk factor for ROP due to early-life gut dysbiosis. This study investigated the association of antibiotic exposure and clinical factors with ROP severity, focusing on high-risk preterm infants that developed ROP not requiring treatment compared to infants with severe ROP that required lasers/injections.

### Methods
This retrospective cohort study included high-risk preterm infants (≤27 weeks GA or ≤750 g BW) admitted to a level III NICU who underwent routine ROP screening. Subjects were stratified into two groups: those requiring treatment for severe ROP (Stage 3 type 1) and those with mild ROP not requiring intervention (Stage 1-2, Stage 3 type 2). Clinical variables including BW, EGA, weight gain rate, days on ventilation, and diagnoses of bronchopulmonary dysplasia (BPD) or necrotizing enterocolitis (NEC) were compared. The Shapiro-Wilk test assessed normality. Continuous variables were analyzed with t-tests or Wilcoxon rank-sum, and categorical variables with Fisher’s exact test. 

### Results
Thirty-four infants met inclusion criteria (23 no treatment, 11 treatment). No statistically significant differences were observed between groups in BW, EGA, weight gain rate, days on ventilation, delivery method, or incidence of BPD or NEC. However, infants requiring treatment for severe ROP had a median of 29 days of antibiotic exposure, compared to 9.0 days in the no treatment group with ROP (p<0.05, Wilcoxon rank-sum). The significant association between prolonged antibiotic exposure and ROP requiring treatment suggests a potential role for microbiome disruption or immune modulation in ROP pathogenesis. 

### Conclusion
These findings suggest that extended antibiotic exposure in high-risk pre-term infants may be associated with increased ROP severity requiring intervention. Alterations in the gut microbiome, potentially mediated by antibiotic use, may trigger downstream effects on immune regulation and signaling pathways. As the gut-retina axis continues to emerge as a key mediator of retinal vascular development, future studies should integrate microbiome profiling and metabolomics to elucidate this mechanistic relationship. 


Prolonged Antibiotic Exposure Associated with Increased Severity of Retinopathy of Prematurity (ROP) Requiring Treatment

### Introduction
Accelerated brain aging can lead to cognitive decline, as morphological changes occur in the brain. We hypothesize that lower social engagement and higher geriatric depression in older adults pose a greater risk for accelerated brain aging and thus a higher brain age gap (BAG).

### Methods
Participants in the AGES study, aged 66 to 96, were surveyed on depression and social engagement at baseline and again after approximately five years. The Geriatric Depression Scale and monthly leisure activity participation were used as measures. Depression scores of 0–5 were categorized as normal/low risk, and scores of 6–15 as moderate/severe risk. For social engagement, each point on the leisure variable corresponded to four leisure activities per month; then categorized into four groups: None (0), Low (0–2), Medium (2–5), and High (5+). Each measure was analyzed using BAG as the dependent variable. 

### Results
Depression predicted higher BAG at baseline (P< 0.013), follow up (P <0.01) and longitudinally (P< 0.005). Leisure was associated with higher BAG at baseline (P < 0.002), however not at follow-up. A post hoc Tukey test confirmed individuals in the "None" category differed significantly from those in the other leisure groups (P < 0.01). No significance was found longitudinally for leisure on BAG.

### Conclusion
Depression has a significant impact on BAG in healthy older adults. Social engagement significantly influences brain aging at baseline, though this effect is not sustained over time; suggesting early intervention may be protective.


Psychosocial Predictors of Accelerated Brain Aging: A Study of Depression and Social Engagement in Healthy Older Adults

### Background
Anxiety disorders affect one in three people worldwide, yet current treatments, centered on brain neurotransmitters, fail many patients and often cause undesirable side effects. While these therapies act centrally, growing evidence suggests that emotional states are also influenced by signals from peripheral organs. We identify asprosin, a fasting-induced hormone secreted by adipose tissue, as a direct endocrine driver of anxiety. Asprosin crosses the blood-brain barrier and binds protein tyrosine phosphatase receptor delta (PTPRD), a neuronal receptor enriched in hippocampal neurons and genetically linked to anxiety risk. This work defines the first hormone–receptor circuit linking energy state to emotional behavior, one that is peripheral, mechanistically distinct, and therapeutically actionable.

### Methods
We manipulated the asprosin-Ptprd signaling axis in mice using five approaches: (1) viral overexpression of asprosin (Ad5-FBN1 or AAV8-asprosin); (2) peripheral neutralization with an anti-asprosin monoclonal antibody (mAb); (3) genetic loss-of-function models, including Fbn1NPS/+ mice (asprosin-deficient) and Ptprd+/- mice; (4) pharmacologic inhibition using 7-butoxy-illudalic acid (7-BIA), a selective Ptprd inhibitor; and (5) stereotactic Cre-mediated deletion of Ptprd in specific brain regions. Anxiety-like behavior was quantified across well-validated assays: open field, light–dark, and elevated plus maze, under both basal conditions and chronic stress paradigms. Asprosin binding was assessed using alkaline phosphatase-tagged ligands, and whole-cell patch-clamp electrophysiology evaluated neuronal excitability.

### Results
Reducing asprosin signaling through - genetic asprosin deficiency, pharmacologic sequestration with a monoclonal antibody, partial Ptprd loss and pharmacologic Ptprd inhibition - reduced baseline anxiety-like behavior across multiple assays. Conversely, elevating asprosin with viral overexpression increased baseline anxiety. When anxiety was induced using chronic stress paradigms, circulating asprosin surged, found to be driven by catecholamine release. Mechanistically, recombinant asprosin depolarized ventral CA1 pyramidal neurons and doubled their firing rate via a Ptprd-dependent, synapse-independent process. Region-specific deletion studies confirmed that Ptprd in ventral CA1 was necessary for stress-induced anxiety, identifying this subregion as the key node mediating asprosin-driven emotional changes.

### Conclusion
This study reframes anxiety as a hormonally gated state regulated by a defined adipose-to-brain endocrine axis. The asprosin–Ptprd pathway operates independently of classical neurotransmission, offering dual therapeutic targets: a peripheral hormone and its central receptor. Our findings highlight the body’s peripheral pathways as an untapped source of insight and innovation in neuropsychiatric disease. It establishes the mechanistic foundation for the first hormone-based anxiolytic, a strategy that is translatable, safe, and designed to reach the millions of patients for whom current drugs fall short.


A hormone circuit from fat to hippocampus drives a novel, druggable anxiety pathway

Vaccination remains one of the most effective strategies of modern medicine in controlling infectious disease outbreaks. However, numerous case reports have described ocular adverse events following administration of COVID-19, influenza, and herpes zoster vaccines. These manifestations range from mild inflammation to vision-threatening complications, including Graves’ orbitopathy, uveitis, optic neuropathies, acute retinal necrosis, retinal vascular occlusions, corneal graft rejection, and cranial nerve palsies. This systematic review was conducted according to PRISMA 2020 guidelines and included 143 studies retrieved from PubMed in February 2025. Articles were screened and categorized by anatomical location and type of ocular manifestation. Many cases resolved with corticosteroids, antivirals, or conservative management; however, a subset of patients experienced persistent vision loss, structural damage, or recurrence. While most cases showed a temporal association rather than definitive causality, proposed mechanisms include molecular mimicry, bystander T-cell activation, and dysregulated cytokine responses in genetically predisposed individuals. Although rare, clinicians should remain aware of these pos-sible adverse effects and monitor high-risk patients accordingly.

A systematic review of vaccine-associated ocular adverse events: Patterns, Pathogenesis, and Public Health Considerations

Background
Hematopoietic stem cells (HSCs) sustain lifelong blood and immune cell supply through their ability to self-renew and generate diverse cell lineages, beginning with the HSCs and progressing through multipotent progenitors (MPPs) and increasingly lineage-restricted intermediates. These transitions remain incompletely understood, particularly the mechanism involved in lineage priming and the timing within a spectrum of MPPs. IKAROS (Ikzf1), a zinc-finger DNA binding factor, is first expressed in the HSC and increases with lymphoid lineage specification. IKAROS proteins interact with chromatin remodeling complexes during lymphoid lineage differentiation, yet their precise role at the onset of hematopoiesis is not defined. We investigated whether IKAROS alters chromatin structure and organization in the nuclear space and how it influences lineage potentials of the earliest progenitors. 

Methods
With IKAROS-knockout and wild-type mice, we used fluorescence-activated cell sorting (FACS) to obtain early progenitor subsets from the bone marrow, including the long- and short-term HSCs, MPPs (from LSK: lineage-/loSca1+c-Kit+), and erythro-myeloid restricted precursors (from LK: lineage-/loSca1+c-Kit-). We performed single-cell RNA sequencing (scRNAseq), single-cell Multiome (scRNAseq and scATACseq/Assay for Transposase-Accessible Chromatin), and Hi-C assays to assess gene expression, chromatin accessibility at regulatory sites (e.g. enhancers and promoters), and 3D genome organization, respectively. Novel bioinformatic approaches were developed to integrate transcriptomic and epigenetic data.

Results
In IKAROS-deficient LSK populations, lymphoid-primed progenitors (CD150-CD48+Flt3+IL7R+) were markedly reduced, while myeloid-primed subsets (CD150-CD48+CD16/32+) were increased. Meanwhile, heterozygous deletions demonstrated haploinsufficiency with similar but milder effects, providing a working model for IKAROS as a molecular regulator for hemo-lymphopoiesis.

With our scMultiome and scRNAseq datasets, integration of MPPs based solely on scATACseq data yielded clearer cell type segregation than scRNAseq or integrated analyses (scRNAseq and scATACseq), reflecting a greater significance of chromatin accessibility over gene expression at this cell stage. Loss of IKAROS led to decreased accessibility at lymphoid-associated transcription factor binding sites and increased accessibility at myeloid sites, suggesting a shift in lineage potential driven by chromatin-level regulation and potential antagonism with myeloid programs. Ongoing 3C (Hi-C) studies examine the influence of IKAROS on lineage-specific 3D organization that appears to precede lineage restrictions.

Conclusion
Our study shows that IKAROS, a key regulator of early hemo-lymphopoiesis, is required for chromatin access at lineage-specific regulatory sites and three-dimensional genome organization. These findings highlight the importance of epigenetic mechanisms in governing early blood cell fates and suggest a new model of blood cell differentiation through lineage-specific epigenetic programs operating prior to lineage specification.


IKAROS-based chromatin regulation on early hematopoietic lineage trajectories

### Background
Despite the success of antiviral treatment for HIV-1 infection, people living with HIV (PWH) have persistent gastrointestinal inflammation which contributes to continued comorbidity. HIV-1 associated gut pathogenesis includes both structural and immunological changes resulting in local inflammation and increased bacterial translocation. In our prior study we observed that in PWH, higher frequencies of a serine protease called Granzyme B (GZB) were associated with greater abundance of potentially inflammatory bacteria. Moreover, enteric bacteria were shown to induce higher frequencies of GZB expressing gut CD4+ T cells. GZB is classically utilized by cytotoxic T cells to induce apoptosis but has additional functions of interest including inflammatory cytokine activation. Currently, significant gaps remain in how GZB affects inflammatory cytokine profiles in the gut. Here we aim to assess how GZB produced in response to enteric bacteria exposure drives gut associated inflammatory cytokine production in a gastrointestinal in vitro model.

### Methods
We utilized our previously established human gut lamina propria mononuclear cell (LPMCs) in-vitro model. LPMCs were stimulated with commensal Escherichia coli (E. coli) lysate in the presence of a cell permeable GZB inhibitor or extracellular anti-GZB blocking antibody. Levels of TNFα, IL-1α, IL-18, and IL-1β, which have been previously shown to be produced in response to exposure to granzymes, were measured by ELISA. Measurement after 48 hours was determined to be the optimal observation time. 

### Results
Exposure of LPMC’s to E. coli for 48 hours induced significantly higher levels of secreted GZB with measurable activity compared to LPMCs that were not exposed to E. coli. Secreted TNFα, IL-1α, IL-18, and IL-1β, and cell associated IL-1α were also increased. In the presence of cell permeable GZB inhibitor, intracellular and extracellular GZB activity was significantly inhibited, and cytokine production decreased to levels similar to unstimulated conditions. In the presence of extracellular anti-GZB blocking antibody, only extracellular GZB activity was significantly inhibited, however E. coli stimulated cytokine production was not reduced.

### Conclusion
Simultaneously blocking of both extracellular and intracellular GZB activity in response to E. coli stimulation of LPMCs in-vitro resulted in decreased production of inflammatory cytokines while inhibition of exclusively extracellular GZB did not attenuate production. This suggests that intracellular GZB, either produced or taken up by immune cell populations is the primary driver for enhancing microbe-induced inflammatory cytokine production within gut LPMCs. Treatments targeting intracellular Granzyme B function could be used in the future to better prevent and control inflammatory gut conditions.


The Role of Granzyme B on Inflammatory Cytokine Production by Human Gut Lamina Propria Mononuclear Cells

### Background
Ulcerative colitis (UC) is a chronic, relapsing and remitting immune mediated condition requiring long-term therapy. Moderate to severe disease is managed using steroids, sulfasalazine, thiopurines, biologicals (anti-tumor necrosis factor, anti-integrins and anti-interleukin IL 12/23) and small molecules (Janus kinase inhibitors, sphingosine-1-receptor modulators). Ustekinumab (UST) is a IgG1 monoclonal antibody acting on IL 12/23 recently authorized to treat moderate to severe UC that is not responsive to other biologic medicines. There remains an unmet need in management of UC despite growing availability of therapeutic agents. Current treatment algorithms use a standard approach for all patients, but targeted therapies are required for better outcomes. This study's goal is to determine the safety and effectiveness of UST therapy in moderate to severe UC. We also noted the clinical and endoscopic improvement with maintenance of clinical and steroid free remission across multiple databases to strengthen reproducibility. 

### Methods
This systematic review followed the Preferred Reporting Items for Systematic Review and Meta Analysis (PRISMA) 2020 guidelines. Relevant literature was retrieved from PubMed, PubMed Central, Cochrane Library, Science Direct and Google Scholar. Articles published in English within the last 5 years (2020 to 2025) were included. Quality assessment tools were applied to ensure the quality of evidence-based medicine that will be utilized to develop a conclusion and direct future review. 

### Results
The studies analysed showed a superiority of UST in induction and maintenance of remission in active, difficult to treat UC. Our findings indicate that reduction in Mayo score with improvement in C-reactive protein (CRP) and fecal calprotectin (fCal) can be used to assess a reduction in inflammatory burden and response to treatment. Histo-endoscopic mucosal healing also provides a long-term clinical assessment of reduction in disease burden. All safety events which led to drug discontinuation and malignancy were similar for UST therapy and placebo. 

### Conclusion
UST as a treatment option for moderate to severe UC can provide an alternative avenue in development of patient centric targeted therapies. Further research targets should include formulation of a standard dosing regimen and evaluation of long-term safety profile of the drug. There also remains an unmet need in comparative analysis of UST treatment with other available therapeutic options, especially biologic agents and effect on extra-intestinal manifestations.

Efficacy and Safety of Ustekinumab in Treatment of Ulcerative Colitis: A Systematic Review

### Background
African American women experience higher breast cancer mortality and are more frequently diagnosed with aggressive tumor subtypes compared to other racial and ethnic groups. Despite advances in cancer genomics, the absence of population-specific diagnostic tools contributes to persistent disparities in clinical outcomes. Circular RNAs (circRNAs) are stable, non-coding RNAs with emerging potential as non-invasive biomarkers in cancer detection and profiling. This study aims to identify tumor-associated circRNAs in African American breast cancer patients using a circRNA analysis pipeline. Discovering circRNA biomarkers specific to African American patients is a key step toward advancing precision oncology and achieving equity in cancer diagnostics and treatment.

### Methods
Serum samples from 35 breast cancer patients and 15 healthy female controls were obtained from the Prisma Health Cancer Institute Biorepository. Following cell-free RNA isolation and circRNA enrichment, full-length circRNA libraries were prepared using the circFL-seq protocol and sequenced using Oxford Nanopore long-read technology. After basecalling and adapter trimming, reads were aligned to the GRCh38 human reference genome. Differential expression analysis using edgeR identified circRNAs associated with cancer status. Expression profiles were compared to public circRNA datasets from individuals of European ancestry to assess race-associated differences. 

### Results
Differential gene expression analysis identified 11 circRNAs associated with race, 27 with tumor status, and 4 showing a race-tumor interaction, revealing race-specific differences in breast tumor biology. Among these, circRNAs from REG3A, a secreted lectin involved in inflammatory signaling and epithelial-mesenchymal transition (EMT), were upregulated in African-American tumors. REG3A drives tumor progression through STAT3 and mTOR activation. Similarly, circRNAs from REG1A, a secreted lectin involved in immune modulation, were upregulated and are linked to tumor progression and resistance to immune surveillance. CircRNAs from CTNNA2, a cell adhesion gene, were upregulated, indicating altered adhesion signaling and a potential regulatory role in tumor progression. In addition, AC011754.1, a long noncoding RNA was also differentially expressed and may contribute to race-specific tumor regulation.

### Conclusion
This study identifies a race-specific gene expression profile in African-American breast cancer involving dysregulation of immune and epithelial pathways. CircRNAs from REG1A, REG3A, CTNNA2, and AC011754.1 may act as molecular drivers of aggressive tumor phenotypes and serve as race-conscious diagnostic and therapeutic biomarkers. CircRNAs regulate gene expression by blocking microRNAs, limiting their ability to suppress targets involved in proliferation, invasion, and immune response. These findings highlight a critical gap in cancer genomics and underscores the need to integrate race-informed molecular data into precision oncology to drive equitable biomarker discovery and improve outcomes in underrepresented populations.

Uncovering Race-Specific CircRNA Biomarkers in African American Breast Cancer Patients

### Background
Prior studies suggest that patient-reported allergies (PRAs) may correlate with poorer surgical outcomes, including greater psychological distress, increased postoperative pain, and reduced mobility in orthopedic populations. However, the relationship between PRAs and outcomes after lumbar interbody fusion (LIF) remains unclear. This study evaluates the association between PRAs and postoperative pain, mobility, and functional improvement following LIF. 

### Methods
A retrospective review was conducted for patients who underwent elective LIF for degenerative spine pathology between November 2019 and January 2023. Patients were grouped by the presence of PRAs (n=242) or no known drug allergies (NKDA; n=83). Baseline demographics, psychiatric history, preoperative opioid use, and reported allergies—categorized as medical or environmental—were recorded. Primary outcomes included one-year changes in Patient-Reported Outcomes Measurement Information System (PROMIS) overall and mental health scores, and Oswestry Disability Index (ODI). Secondary outcomes included postoperative visual analog scale (VAS) pain scores and Activity Measure for Post-Acute Care (AMPAC) scores. Associations were assessed using univariate and multivariate regression models. Receiver operating characteristic (ROC) analysis evaluated the predictive value of PRA count for achieving minimal clinically important difference (MCID) in PROMIS and ODI scores. 

### Results
Patients with PRAs were more likely to be female (57%, p=0.002) and have psychiatric histories (0.9 ± 1.1 vs. 0.7 ± 1.0, p=0.02). PRA patients had greater improvement in PROMIS overall (11.5 ± 12.8 vs. 6.7 ± 10.2, p=0.048) and mental health scores (13.5 ± 18.7 vs. 6.6 ± 14.6, p=0.026). ODI improvement did not differ significantly. PRA count was not associated with VAS, AMPAC, or MCID achievement in PROMIS or ODI. Increasing fusion levels negatively impacted AMPAC scores (-1.096 per level fused, p<0.05) but not VAS. Psychiatric history reduced odds of achieving MCID for PROMIS physical and ODI scores, while preoperative opioid use had no impact on pain, mobility, or MCID outcomes. ROC analysis showed poor predictive value of PRA count for MCID (AUC <0.600).

### Conclusion
PRAs were not associated with worse outcomes following LIF. Instead, patients with PRAs experienced greater improvements in PROMIS, particularly in mental health. PRA count did not affect postoperative pain, mobility, or MCID achievement. These findings suggest that the presence or quantity of PRAs should not deter clinicians from recommending lumbar fusion surgery.


The Influence of Patient-Reported Allergies on Postoperative Mobility, Pain, and Long-Term Outcomes following Lumbar Interbody Fusion

### Background
Deep vein thrombosis (DVT) is a major healthcare burden with significant morbidity and mortality. Anticoagulation therapy is the current treatment of choice. However, this approach can sometimes lead to only partial resolution, allowing for thrombus organization. This can result in the development of post-thrombotic syndrome (PTS), a sequela of chronic DVT that includes symptoms such as limb pain, cramping, edema, stasis dermatitis, or even venous ulceration. There is currently no effective treatment for PTS, and as a consequence, it can become a lifelong problem that significantly impairs a patient’s quality of life. Here, we examine whether the local delivery of non-thermal irreversible electroporation (IRE) can impede thrombus organization and fibrosis by achieving cellular ablation and allowing time for natural thrombus resolution to occur.

### Methods
In vitro and ex vivo methods were utilized to investigate the thermal and ablative effects of IRE. A microfluidics device was seeded with neutrophils and endothelial cells to determine voltage thresholds for selective, safe ablation. Rheological analysis was conducted to evaluate the impact of IRE on blood coagulation. Porcine blood clots, generated in a syringe model, were used to assess red blood cell and fibrin architecture following IRE treatment. These models guided the optimization of IRE parameters for subsequent in vivo studies. Calibrated pulsed electric fields were then delivered locally using a tweezer-style electrode system to target acute DVT lesions induced in the femoral veins of rat and swine models. Animals were monitored for three or seven days post-treatment. Histological, immunohistochemical, and molecular analyses were performed to assess thrombus organization, vessel integrity, luminal cellularity, cytokine expression, and inflammatory or fibrotic markers following IRE-treatment.

### Results
IRE-treated blood demonstrated preserved clotting kinetics and minimal hemolysis, supporting the safety and efficacy of blood cell ablation using IRE. Histologic analysis of IRE-treated animal femoral vein segments revealed significantly reduced cellular proliferation, collagen deposition, and angiogenesis. IRE-treated tissues also exhibited lower expression of pro-fibrotic, pro-thrombogenic, and pro-coagulant markers compared to controls. Across both models, vessel wall thickness and luminal architecture remained intact, confirming the non-destructive nature of IRE, with no evidence of structural wall damage or aneurysm formation.

### Conclusion
These findings suggest that IRE may serve as a promising adjunctive therapy to anticoagulation by preventing the organization of acute thrombi into chronic DVT. This could ultimately reduce the incidence of post-thrombotic syndrome and improve long-term patient outcomes.

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Prolonged Antibiotic Exposure Associated with Increased Severity of Retinopathy of Prematurity (ROP) Requiring Treatment

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