Expansion Of Pool Research Articles

FGF2 promotes the expansion of parietal mesothelial progenitor pools and inhibits BMP4-mediated smooth muscle cell differentiation.

Mesothelial cells, in the outermost layer of internal organs, are essential for both organ development and homeostasis. Although the parietal mesothelial cell is the primary origin of mesothelioma that may highjack developmental signaling, the signaling pathways that orchestrate developing parietal mesothelial progenitor cell (MPC) behaviors, such as MPC pool expansion, maturation, and differentiation, are poorly understood. To address it, we established a robust protocol for culturing WT1+ MPCs isolated from developing pig and mouse parietal thorax. Quantitative qPCR and immunostaining analyses revealed that BMP4 facilitated MPC differentiation into smooth muscle cells (SMCs). In contrast, FGF2 significantly promoted MPC progenitor pool expansion but blocked the SMC differentiation. BMP4 and FGF2 counterbalanced these effects, but FGF2 had the dominant impact in the long-term culture. A Wnt activator, CHIR99021, was pivotal in MPC maturation to CALB2+ mesothelial cells, while BMP4 or FGF2 was limited. Our results demonstrated central pathways critical for mesothelial cell behaviors.

Expansion of the Pancreas Transplant Recipient Pool: Appropriate for Most or Are There Limits?

Expansion of the Pancreas Transplant Recipient Pool: Appropriate for Most or Are There Limits?

Pushing the Survival Bar Higher: Two Decades of Innovation in Lung Transplantation.

Survival after lung transplantation has significantly improved during the last two decades. The refinement of the already existing extracorporeal life support (ECLS) systems, such as extracorporeal membrane oxygenation (ECMO), and the introduction of new techniques for donor lung optimization, such as ex vivo lung perfusion (EVLP), have allowed the extension of transplant indication to patients with end-stage lung failure after acute respiratory distress syndrome (ARDS) and the expansion of the donor organ pool, due to the better evaluation and optimization of extended-criteria donor (ECD) lungs and of donors after circulatory death (DCD). The close monitoring of anti-HLA donor-specific antibodies (DSAs) has allowed the early recognition of pulmonary antibody-mediated rejection (AMR), which requires a completely different treatment and has a worse prognosis than acute cellular rejection (ACR). As such, the standardization of patient selection and post-transplant management has significantly contributed to this positive trend, especially at high-volume centers. This review focuses on lung transplantation after ARDS, on the role of EVLP in lung donor expansion, on ECMO as a principal cardiopulmonary support system in lung transplantation, and on the diagnosis and therapy of pulmonary AMR.

Preparation and arc erosion mechanism of Ni skeleton reinforced Ag-based contact materials with CuO-coated SnO2

The Ag-SnO2 contact material is widely regarded as the most promising environmental friendly electrical contact material. However, during the make and break operations, SnO2 particles rising to the surface can cause increased contact resistance and temperature rise, which affects the service life of the contact material. In this study, a three-dimensional (3D) Ni skeleton reinforced Ag-based contact material with CuO-coated SnO2 are successfully fabricated via powder metallurgy technology. The basic physical properties of the novel contact material were tested and the microstructures and arc erosion morphologies were analyzed using X-ray diffraction (XRD) and scanning electron microscopy (SEM). The research demonstrated that the hardness and electrical conductivity of the novel contact material are 128.9 HV and 46 %IACS, respectively. It can be observed that the SnO2-rich phase is uniformly distributed in the Ag matrix without significant upward after arc erosion, which indicates that the SnO2@CuO core-shell structure effectively enhances the wettability between Ag and SnO2. Meanwhile, the study revealed that the Ni phase uniformly distributed at the interface of the Ag phase during the arc erosion process, indicating that the 3D Ni skeleton structure effectively impedes the expansion of the Ag molten pool and improves the anti-arc erosion performance.

Topography Controls Variability in Circumpolar Permafrost Thaw Pond Expansion

AbstractOne of the most conspicuous signals of climate change in high‐latitude tundra is the expansion of ice wedge thermokarst pools. These small but abundant water features form rapidly in depressions caused by the melting of ice wedges (i.e., meter‐scale bodies of ice embedded within the top of the permafrost). Pool expansion impacts subsequent thaw rates through a series of complex positive and negative feedbacks which play out over timescales of decades and may accelerate carbon release from the underlying sediments. Although many local observations of ice wedge thermokarst pool expansion have been documented, analyses at continental to pan‐Arctic scales have been rare, hindering efforts to project how strongly this process may impact the global carbon cycle. Here we present one of the most geographically extensive and temporally dense records yet compiled of recent pool expansion, in which changes to pool area from 2008 to 2020 were quantified through satellite‐image analysis at 27 survey areas (measuring 10–35 km2 each, or 400 km2 in total) dispersed throughout the circumpolar tundra. The results revealed instances of rapid expansion at 44% (15%) of survey areas. Considered alone, the extent of departures from historical mean air temperatures did not account for between site variation in rates of change to pool area. Pool growth was most clearly associated with upland (i.e., hilly) terrain and elevated silt content at soil depths greater than one meter. These findings suggest that, at short time scales, pedologic and geomorphologic conditions may exert greater control on pool dynamics in the warming Arctic than spatial variability in the rate of air temperature increases.

The spatio-temporal variations of cultivated land compensation efficiency and its influencing factors in mainland China

Cultivated land, for which compensation is a practical approach to safeguarding, is a strategic and scarce resource. Evaluating the cultivated land compensation efficiency and identifying its influencing factors are of great significance for monitoring the effect of such compensation and improving the associated policy. A new multi-dimensional framework for estimating the cultivated land compensation efficiency was proposed. This framework not only emphasized the externality of cultivated land but also incorporated its ecological value. Cultivated land compensation efficiency in mainland China from 2000 to 2021 was estimated using this framework and the global Super-SBM model. The panel Tobit model was also adopted to analyze the factors influencing cultivated land compensation efficiency. The results show that (1) Over the past 22 years, the cultivated land compensation efficiency in mainland China initially declined but subsequently exhibited an upward trend, maintaining an average value of 0.724. (2) On a spatial scale, the cultivated land compensation efficiency exhibited pronounced regional pattern, with higher levels observed in the northeastern and southwestern regions of mainland China and lower levels in the eastern region. The cultivated land compensation efficiency in different provinces has distinctive patterns as well. Generally, the cultivated land compensation efficiency is relatively stable in most provinces, though few illustrate an uptrend. (3) Both the ratio of the population with tertiary education and above to the total population and the ratio of primary sector production to GDP affect cultivated land compensation efficiency positively, with the former being more significant. Conversely, GDP per capita, agricultural water consumption, the area affected by disasters, and the ratio of local expenditure on science, technology and education to total fiscal expenditure affect cultivated land compensation efficiency negatively. Therefore, a set of recommendations has been put forward, encompassing the optimization of provincial inputs and outputs, the reinforcement of inter-provincial coordination and collaboration, and the expansion of the talent pool of funds.

Volumetric Changes in the Choroid Plexus Associated with Spontaneous Intracranial Hypotension in Patients with Spinal CSF Leak.

The choroid plexus contains specialized ependymal cells responsible for CSF production. Recent studies have demonstrated volumetric and perfusion changes in the choroid plexus with age and neurodegenerative disorders, however, volumetric changes in the choroid plexus in low pressure states is not known. The purpose of this study is to evaluate volumetric differences in choroid plexus size in patients with spontaneous intracranial hypotension (SIH) resultant from spinal CSF leaks compared with healthy controls. This was a retrospective, institutional review board-approved study. Patients with MRI evidence of SIH and a spinal CSF leak diagnosed on myelography and subsequently confirmed at surgery were included in this study. All patients included in this study including age-matched healthy controls had a brain MRI performed on a either a 1.5 or 3T scanner with acquisition of 3D T1 postcontrast (eg, BRAVO, MPRAGE, etc). In all patients, the trigonum ventriculi volume, in the atria of the lateral ventricles, was contoured by using Visage-7 segmentation tools on the volumetric postcontrast T1 sequence. A basic 2-tailed t test was used to compare choroid plexus volumes between the 2 groups. Thirty-four patients were included with 17 patients with SIH with spinal CSF leak and 17 healthy control patients who were age- and sex-matched. The mean age of patients was 45 years, standard deviation 14 years. The mean volume of the choroid plexus for patients with SIH with spinal CSF leak was 1.2 cm3 (standard deviation = 0.26) compared with 0.63 cm3 (standard deviation = 0.31) in the control group (P < .0001). Results of this study demonstrate a higher choroid plexus volume in patients with SIH with spinal CSF leak compared with age- and sex-matched healthy controls. This likely reflects compensatory mechanisms to counteract intracranial hypotension by increasing CSF production as well as increased vascularity of the choroid plexus through expansion of the intracranial blood pool.

In situ x-ray imaging to understand subsurface behavior during continuous wave laser drilling

A limited understanding regarding the underlying dynamics and mechanisms of material removal during continuous wave laser drilling has presented significant challenges in achieving precision and process control. To address this, we employed high-fidelity, in situ synchrotron x-ray imaging to reveal previously unknown material behaviors during continuous wave laser drilling with power modulation. Our findings highlight that high-aspect ratio drill holes are achieved when the laser modulation frequency falls within the range of 8–12 kHz, provided that the laser average power and modulation amplitude levels meet the specified limits. Under these conditions, we identified a material removal mechanism driven by incremental accumulation of recoil pressure that gradually pushes material upward from deep within the substrate to the surface. This mechanism manifested as a low-frequency fluctuation in the vapor depression depth, resulting in periodic instances of material ejection. Furthermore, our study underscores that rapid expansion of the melt pool and the widening of the drill hole opening can impede effective material removal by redirecting energy from material ejection to increasing the melt pool size. This investigation contributes essential insights into the subsurface dynamics involved in the drilling of high-aspect ratio holes, furthering our fundamental understanding of this intricate process.

Abstract Tu059: Single-Nucleus Transcriptomics Demonstrates Endothelial Cell Expansion in Failing Human Right Ventricles

Background: Right ventricular failure (RVF) is most commonly observed as a sequela of left ventricular failure (LVF)—for which it more than doubles the risk of mortality. Moreover, isolated RVF is the most common cause of death in pulmonary hypertension and is a leading cause of major adverse events in systemic right ventricle congenital heart diseases. Therapies which effectively treat LVF show poor efficacy for RVF. For example, beta blockade, a cornerstone of LVF therapy, has no efficacy in RVF. Therefore, there is a need for broader exploratory research to identify pathways which are dysregulated in RVF and which could serve as targets for future therapies. Methods/Results: To this end, we performed single-nucleus RNA sequencing (N=11) on RV myocardium from nonfailing or dilated cardiomyopathy (DCM) hearts subgrouped by preserved systolic and diastolic RV function (pRV) or RVF. After cell-type assignment and differential expression analysis, we find a progressive upregulation of pro-angiogenic signaling in vascular endothelial cells (ECs) from nonfailing to pRV and RVF. There is a concomitant expansion of the EC pool from nonfailing to pRV and RVF (EC percentage 5%, 9%,15% for NF, pRV, and RVF; p &lt; 0.05 for one-way ANOVA). We find increased HIF-mediated and VEGF-mediated signaling in these ECs, which may be mediating this expansion. Surprisingly, there is also increased expression of genes regulated by type 1 interferon signaling, which is thought to be anti-angiogenic. Discussion: In summary, we have conducted a single-nuclei transcriptomic study of human RVF and found evidence for increased angiogenic signaling and EC expansion. These findings are significant, as the balance of pro-angiogenic and anti-angiogenic factors in RVF is still unclear, with studies in animal models showing conflicting results in terms of changes in macro/microvasculature in RVF. Here, we provide evidence that in human RVF the balance tends to lead toward a pro-angiogenic phenotype, even in dysfunctional RVs. Orthogonal studies to validate the causal nature of these observed changes in pathogenesis of RVF are currently ongoing.

Understanding the interplay between dNTP metabolism and genome stability in cancer.

The size and composition of the intracellular DNA precursor pool is integral to the maintenance of genome stability, and this relationship is fundamental to our understanding of cancer. Key aspects of carcinogenesis, including elevated mutation rates and induction of certain types of DNA damage in cancer cells, can be linked to disturbances in deoxynucleoside triphosphate (dNTP) pools. Furthermore, our approaches to treat cancer heavily exploit the metabolic interplay between the DNA and the dNTP pool, with a long-standing example being the use of antimetabolite-based cancer therapies, and this strategy continues to show promise with the development of new targeted therapies. In this Review, we compile the current knowledge on both the causes and consequences of dNTP pool perturbations in cancer cells, together with their impact on genome stability. We outline several outstanding questions remaining in the field, such as the role of dNTP catabolism in genome stability and the consequences of dNTP pool expansion. Importantly, we detail how our mechanistic understanding of these processes can be utilised with the aim of providing better informed treatment options to patients with cancer.

Machine perfusion in transplantation surgery

The use of machine perfusion in solid organ transplantation has developed tremendously worldwide in recent years. Although the number of randomized controlled trials in the field of organ preservation is still limited, machine perfusion has been shown to be superior to static cold storage of donor organs. Various devices for clinical use with hypothermia or normothermia are already available for most organs. Whether and which perfusion strategy is superior to the others is the subject of current clinical research. This also applies to the further evaluation of possible synergistic effects in the sequential use of the various protocols. The common goal of all dynamic perfusion technologies is to optimize organ preservation between removal and transplantation. By testing the quality of marginal donor organs prior to transplantation, it should also be possible to use these organs without exposing the patient to increased risk. This can lead to a significant expansion of the donor pool. This is particularly important in Germany, where there is an ongoing shortage of organs and restrictive legislation regarding the expansion of the donor pool. Furthermore, the perfusion technology offers the possibility to serve as a platform for other ex situ and in situ therapies on isolated organs. In addition to the conditioning of pre-damaged organs for transplantation, this could lead to further applications in the context of targeted organ therapies and also to improved transplant logistics in the future.

Trends of liver transplantation in Asia.

Liver transplantation (LT) in Asia started comparatively early in 1964, just 1year after Starzl's trail-blazing first attempt. Despite the quick start, LT was slow to develop in this region. Limited access to universal healthcare, lack of public understanding and support as well as the absence of strong legislation, on a backdrop of a wide range of diverse social, religious, economic and cultural background are all contributory factors. Through strong administrative efforts, the number of DDLTs in selected Asian countries has been slowly rising in recent years. However, Asians are generally still less likely to donate organs than Caucasians after death. The strong demand for LT with limited access to deceased organs has, therefore, led to constant need for innovation in LT this region, with the pioneering of various LDLT techniques and safe expansion of donor pool being driven primarily by Asian centers. Familiarity and the development of technical expertise in donor surgery have also resulted in Asian centers repeatedly pushing the boundaries on minimally invasive donor and recipient surgery. In this article, we focus on the past and present states of LT in Asia and explore the future trends of LT in this region.

Abatacept for acute graft-versus-host disease prophylaxis after unrelated donor hematopoietic cell transplantation

AbstractAbatacept plus calcineurin inhibitors/methotrexate (CNI/MTX) is the first US Food and Drug Administration (FDA)-approved regimen for acute graft-versus-host disease (aGVHD) prophylaxis during unrelated-donor hematopoietic cell transplantation (URD-HCT). Using Center for International Blood and Marrow Transplant Research data, we investigated its impact in patients receiving 7/8 HLA-mismatched unrelated donor (MMUD) or 8/8 HLA-matched unrelated donor (MUD) URD-HCT between 2011 and 2018. Primary outcomes included day-180, 1-year, and 2-year overall survival (OS) and relapse-free survival (RFS) for abatacept + CNI/MTX vs CNI/MTX, CNI/MTX + antithymocyte globulin (ATG), and posttransplant cyclophosphamide-based prophylaxis (PT-Cy). For 7/8 MMUDs, day-180 OS (primary end point supporting FDA approval) was significantly higher for abatacept + CNI/MTX vs CNI/MTX (98% vs 75%; P = .0028). Two-year RFS was significantly higher for abatacept + CNI/MTX vs CNI/MTX (74% vs 49%; P = .0098) and CNI/MTX + ATG (77% vs 35%; P = .0002), and similar vs PT-Cy (72% vs 56%; P = .1058). For 8/8 MUDs, 2-year RFS for abatacept + CNI/MTX was numerically higher vs CNI/MTX (63% vs 52%; P = .1497), with an improved hazard ratio (HR) of 0.46 (0.25-0.86), and vs CNI/MTX + ATG (66% vs 55%; P = .1193; HR, 0.39 [0.21-0.73]), and was similar vs PT-Cy (68% vs 57%; P = .2356; HR, 0.54 [0.26-1.11]). For 7/8 MMUD and 8/8 MUD recipients, abatacept + CNI/MTX prophylaxis improved survival outcomes vs CNI/MTX and CNI/MTX + ATG; outcomes were similar to PT-Cy–based regimens. Abatacept + CNI/MTX may facilitate unrelated donor pool expansion for HCT.

Transdifferentiation is temporally uncoupled from progenitor pool expansion during hair cell regeneration in the zebrafish inner ear.

Death of mechanosensory hair cells in the inner ear is a common cause of auditory and vestibular impairment in mammals, which have a limited ability to regrow these cells after damage. In contrast, non-mammalian vertebrates, including zebrafish, can robustly regenerate hair cells after severe organ damage. The zebrafish inner ear provides an understudied model system for understanding hair cell regeneration in organs that are highly conserved with their mammalian counterparts. Here, we quantitatively examine hair cell addition during growth and regeneration of the larval zebrafish inner ear. We used a genetically encoded ablation method to induce hair cell death and we observed gradual regeneration with correct spatial patterning over a 2-week period following ablation. Supporting cells, which surround and are a source of new hair cells, divide in response to hair cell ablation, expanding the possible progenitor pool. In parallel, nascent hair cells arise from direct transdifferentiation of progenitor pool cells temporally uncoupled from supporting cell division. These findings reveal a previously unrecognized mechanism of hair cell regeneration with implications for how hair cells may be encouraged to regenerate in the mammalian ear.

Regional variation in donation after circulatory death heart allograft utilization

ObjectiveRandomized data support transplantation of hearts from donors after circulatory death. This may lead to a sizeable increase in the donor pool. Regional variations in donors after circulatory death heart use were examined to help elucidate barriers to donor pool expansion. MethodsThe United Network for Organ Sharing deceased donor dataset was queried for adult (age ≥ 18 years) donors after circulatory death donors of at least 1 organ between January 2020 and December 2023. Donors were stratified by the extent their respective cardiac allografts progressed through the donation process. United Network for Organ Sharing region-level use rates and annual trends were assessed. ResultsOf 17,239 adult donors after circulatory death donors who donated at least 1 organ for transplant during the study period, 1196 (9.4%) were heart donors. Regional donors after circulatory death heart donor pursuit rates ranged from 97% to 100%, consent attainment rates from 94% to 99%, and heart recovery rates from 5% to 10%. The transplantation rate of recovered organs ranged from 90% to 97%. Multivariable logistic regression demonstrated United Network for Organ Sharing region to be independently associated with donors after circulatory death heart use after controlling for baseline differences in donor risk. ConclusionsTransplantation of donors after circulatory death heart allografts has increased in the United States since 2020, but the overall number of hearts procured and transplanted from donors after circulatory death donors remains low. The operational barriers to transplantation of donors after circulatory death hearts require further investigation. Further, significant regional variation exists regarding rates of progression of donors after circulatory death hearts through the donation process. Sharing of successful practices among Organ Procurement Organizations and transplant centers will facilitate maximal use of this new donor pool.

Antimicrobial resistance: Molecular drivers and underlying mechanisms

Ancient humans evaded lethal, tropical infections by migrating away from pathogen reservoirs to colder regions where the climate served as a physiological barrier to growth of pathogenic microorganisms. In the contemporary world, aversion of bacterial infections is being dominantly governed by a plethora of antimicrobial drugs which are deemed to be a boon to the society owning to their instant effectiveness, fewer stringent containment and transportation requirements, wider accessibility and economic feasibility. Nonetheless, antibiotic effectivity gradually declined as more microbes began evolving tolerance mechanisms (drug inactivation, drug efflux, drug target modification and more) against them. Invention of sensitive technologies paved way for fresh revelations including how conjugative plasmids in tandem with other mobile genetic elements (MGEs) contribute to the expansion of AMR gene pool. In this commentary, we revise the multifaceted processes associated with the origin (in microbial and human populations), advancement (antibiotic misuse, excessive use of antimicrobial resistance genes as selective markers in cloning pursuits) and dissemination of AMR, thereby, resolving confusions, unveiling new facts and targets that could lay the groundwork for novel therapies.

Optimizing DCD Liver Grafts With Prolonged Warm Ischemic Time Using Stabilized Plasmin in a Static Cold Storage Orthotopic Rat Liver Transplant Model.

The clinical success of liver transplantation has led to increased demand, requiring further expansion of the donor pool. Therapeutic interventions to optimize organs from donation after circulatory death (DCD) have significant potential to mitigate the organ shortage. Dysfunction in DCD liver grafts is mediated by microvascular thrombosis during the warm ischemic period, and strategies that reduce this thrombotic burden may improve graft function. We hypothesized that the administration of the fibrinolytic enzyme plasmin to the donor organ during the cold storage period would reduce the thrombotic burden and improve DCD liver graft function. In 2 separate cohorts, 32 syngeneic orthotopic rat liver transplants were performed in Lewis rats. Livers were procured from donors with 45 min of warm ischemic injury. Liver grafts were flushed with histidine-tryptophan-ketoglutarate preservation solution mixed with either plasmin (experimental group) or albumin (control group). All investigators were blinded to treatment group. After preparing the liver for implant using a modified cuff technique, the liver was stored for 1 h by static cold storage at 4 °C. Immediately before implantation, the liver graft was flushed, and this effluent was analyzed for fibrin degradation products to determine graft clot burden. Twenty-four hours following transplantation, animals were euthanized, and samples were collected. Recipient survival was significantly higher for DCD liver grafts treated with plasmin compared with control. Moreover, histology of liver graft tissue immediately before implant reflected significantly reduced congestion in plasmin-treated livers (score, mean ± SD: 0.73 ± 0.59 versus 1.12 ± 0.48; P = 0.0456). The concentration of fibrin degradation products in the final flush before implantation was significantly reduced in plasmin-treated livers (743 ± 136 versus 10 919 ± 4642 pg/mL; P = 0.0001), reflecting decreased clot burden in the graft. The present study demonstrates that plasmin improves survival and may reduce thrombotic burden in DCD liver grafts with prolonged warm ischemic injury, meriting further study.

Decrease in MJO Predictability Following Indo–Pacific Warm Pool Expansion

AbstractThe characteristics of the Madden–Julian oscillation (MJO) have changed and are projected to continue changing with the expansion of the Indo–Pacific warm pool, which is the Earth's largest region of warm sea surface temperatures (SSTs). However, the likelihood of a change in MJO predictability following warm pool expansion remains unaddressed. Therefore, this study investigated the effect of warm pool expansion on MJO variability and predictability using the highly idealized aquaplanet configuration of Community Earth System Model 2 (CESM2). By expanding the warm pool in the Indo–Pacific, MJO‐like waves become more regionally confined, short‐lived convective events with weaker magnitude and less robust eastward propagating signals, possibly due to stronger zonal SST gradients and wider meridional widths of the warm pool. Perfect‐model ensemble forecast experiments revealed that the MJO predictability decreased by approximately 5 days, the forecast error proliferated, and the signal rapidly reduced following warm pool expansion.

The Ugly: Metastatic Colon Cancer—Surgical Options

AbstractOver 50% of patients with colorectal cancer develop metastatic disease. Although systemic therapy remains the backbone of palliative treatment, select patients may be candidates for surgical resection with curative intent. Given increasing evidence of the association between metastasectomy and prolonged survival, surgery has acquired an increasingly central role in the management of liver, lung, and peritoneal metastases. This is compounded by accumulating advances in local and systemic treatments that have allowed for expansion of the resectability pool, bringing the potential for curative surgical treatment to increasing numbers of patients with stage IV disease. However, as the boundaries of resectability are pushed, patient selection and consideration of tumor-related and technical factors are imperative to the identification of patients for whom surgery would be of the greatest benefit.

BIOM-04. ALTERED IMMUNE ACTIVATION AND REDUCED LYMPHOPOIESIS IN TREATMENT NAÏVE PEDIATRIC BRAIN TUMOUR PATIENTS

Abstract Pediatric central nervous system (CNS) tumors are the most common solid tumor in children. Despite improvements in diagnostic and therapeutic approaches over time, treatment effectiveness remains unsatisfactory. Optimal immune function is critical to protect against development and dissemination of cancer and to offer the ideal conditions for the success of anticancer treatment. Here we analyzed the peripheral immunological features of patients affected by pediatric brain tumors, the process of de novo T- and B-cell development and its association with the lymphopenia often observed in these patients. Eighty-six steroids-naïve pediatric patients with CNS tumors at the onset of the disease were included in the study. Brain tumors were classified into low-grade gliomas (LGG: n=44, 51%), pediatric-type diffuse high-grade gliomas (pHGG: n=16, 19%), medulloblastoma (n =9, 10%), and other CNS tumors (n =17, 20%). Patient’s peripheral immunological status was analyzed by flow-cytometry and by evaluating T-cell receptor excision circles (TRECs) and kappa-deleting excision circles (KREC) to quantify T- and B-cell neogenesis. Although all patients showed tendencies towards low lymphocyte counts, this effect was particularly evident in pHGG patients. T-cells of pHGG patients displayed a shift from naïve to effector memory phenotype compared to age-matched controls. On the other hand, LGG patients were characterized by an expansion of the T-central memory pool and higher expression of T-cell activation markers. Both patient cohorts exhibited decreased frequency of B-cells with activated phenotype. Interestingly, pHGG patients exhibited reduced thymic function as revealed by reduced levels of the recent thymic emigrant population and TRECs. In addition, LGG and pHGG patients were characterized by lower KREC values, suggesting suboptimal B-cell formation. At diagnosis, pediatric patients with brain tumor show alterations in their immunological status and reduced thymic and medullary lymphopoiesis, particularly pronounced in pHGG, which may contribute to explain the systemic lymphopenia characterizing these patients.