Healthy Tissue Research Articles

ReMIND: The Brain Resection Multimodal Imaging Database

The standard of care for brain tumors is maximal safe surgical resection. Neuronavigation augments the surgeon’s ability to achieve this but loses validity as surgery progresses due to brain shift. Moreover, gliomas are often indistinguishable from surrounding healthy brain tissue. Intraoperative magnetic resonance imaging (iMRI) and ultrasound (iUS) help visualize the tumor and brain shift. iUS is faster and easier to incorporate into surgical workflows but offers a lower contrast between tumorous and healthy tissues than iMRI. With the success of data-hungry Artificial Intelligence algorithms in medical image analysis, the benefits of sharing well-curated data cannot be overstated. To this end, we provide the largest publicly available MRI and iUS database of surgically treated brain tumors, including gliomas (n = 92), metastases (n = 11), and others (n = 11). This collection contains 369 preoperative MRI series, 320 3D iUS series, 301 iMRI series, and 356 segmentations collected from 114 consecutive patients at a single institution. This database is expected to help brain shift and image analysis research and neurosurgical training in interpreting iUS and iMRI.

Systematic dissection of tumor-normal single-cell ecosystems across a thousand tumors of 30 cancer types

The complexity of the tumor microenvironment poses significant challenges in cancer therapy. Here, to comprehensively investigate the tumor-normal ecosystems, we perform an integrative analysis of 4.9 million single-cell transcriptomes from 1070 tumor and 493 normal samples in combination with pan-cancer 137 spatial transcriptomics, 8887 TCGA, and 1261 checkpoint inhibitor-treated bulk tumors. We define a myriad of cell states constituting the tumor-normal ecosystems and also identify hallmark gene signatures across different cell types and organs. Our atlas characterizes distinctions between inflammatory fibroblasts marked by AKR1C1 or WNT5A in terms of cellular interactions and spatial co-localization patterns. Co-occurrence analysis reveals interferon-enriched community states including tertiary lymphoid structure (TLS) components, which exhibit differential rewiring between tumor, adjacent normal, and healthy normal tissues. The favorable response of interferon-enriched community states to immunotherapy is validated using immunotherapy-treated cancers (n = 1261) including our lung cancer cohort (n = 497). Deconvolution of spatial transcriptomes discriminates TLS-enriched from non-enriched cell types among immunotherapy-favorable components. Our systematic dissection of tumor-normal ecosystems provides a deeper understanding of inter- and intra-tumoral heterogeneity.

Secondary Lipid Oxidation Products as Modulators of Calpain-2 Functionality In Vitro.

The objective was to understand the impacts of secondary lipid oxidation products on calpain-2 activity and autolysis and, subsequently, to determine the quantity and localization of modification sites. 2-Hexenal and 4-hydroxynonenal incubation significantly decreased calpain-2 activity and slowed the progression of autolysis, while malondialdehyde had minimal impact on calpain-2 activity and autolysis. Specific modification sites were determined with LC-MS/MS, including distinct malondialdehyde modification sites on the calpain-2 catalytic and regulatory subunits. 2-Hexenal modification sites were observed on the calpain-2 catalytic subunit. Intact protein mass analysis with MALDI-MS revealed that a significant number of modifications on the calpain-2 catalytic and regulatory subunits are likely to exist. These observations confirm that specific lipid oxidation products modify calpain-2 and may affect the calpain-2 functionality. The results of these novel experiments have implications for healthy tissue metabolism, skeletal muscle growth, and post-mortem meat tenderness development.

Selective internal radiation therapy segmentectomy: A new minimally invasive curative option for primary liver malignancies?

Transarterial radioembolization or selective internal radiation therapy (SIRT) has emerged as a minimally invasive approach for the treatment of tumors. This percutaneous technique involves the local, intra-arterial delivery of radioactive microspheres directly into the tumor. Historically employed as a palliative measure for liver malignancies, SIRT has gained traction over the past decade as a potential curative option, mirroring the increasing role of radiation segmentectomy. The latest update of the BCLC hepatocellular carcinoma guidelines recognizes SIRT as an effective treatment modality comparable to other local ablative methods, particularly well-suited for patients where surgical resection or ablation is not feasible. Radiation segmentectomy is a more selective approach, aiming to deliver high-dose radiation to one to three specific hepatic segments, while minimizing damage to surrounding healthy tissue. Future research efforts in radiation segmentectomy should prioritize optimizing radiation dosimetry and refining the technique for super-selective administration of radiospheres within the designated hepatic segments.

Management of biofilm-associated infections in diabetic wounds – from bench to bedside

Abstract Biofilms are complex bacterial colonies embedded in an extracellular matrix. These pose a major obstacle to wound healing and are noticeable in chronic wounds. It protects the bacteria from the host’s immune system and conventional antibiotic treatments. The biofilm’s protective matrix prevents essential nutrients and oxygen from diffusing into the surrounding healthy tissue. In addition, microbes living in biofilms naturally have increased resistance to antibiotics, which reduces the effectiveness of traditional therapies. As such, biofilms serve as persistent reservoirs of infection, which further disrupts the normal course of wound healing. In this review, the current formulation strategies such as hydrogels, polymeric nanoparticles, and nanofibers that are used in wound healing to counteract biofilms have been comprehensively discussed. The formulations have been meticulously designed and developed to disturb the biofilm matrix, prevent the growth of microorganisms, and increase the potency of antimicrobials and antibiotics. The mechanism of action, advantages and limitations associated with the existing formulation strategies have been reviewed. The formulation strategies that have been translated into clinical applications and patented are also discussed in this paper.

A study protocol to characterise pathophysiological and molecular markers of rheumatic heart disease and degenerative aortic stenosis using multiparametric cardiovascular imaging and multiomics techniques.

Rheumatic heart disease (RHD), degenerative aortic stenosis (AS), and congenital valve diseases are prevalent in sub-Saharan Africa. Many knowledge gaps remain in understanding disease mechanisms, stratifying phenotypes, and prognostication. Therefore, we aimed to characterise patients through clinical profiling, imaging, histology, and molecular biomarkers to improve our understanding of the pathophysiology, diagnosis, and prognosis of RHD and AS. In this cross-sectional, case-controlled study, we plan to recruit RHD and AS patients and compare them to matched controls. Living participants will undergo clinical assessment, echocardiography, CMR and blood sampling for circulatory biomarker analyses. Tissue samples will be obtained from patients undergoing valve replacement, while healthy tissues will be obtained from cadavers. Immunohistology, proteomics, metabolomics, and transcriptome analyses will be used to analyse circulatory- and tissue-specific biomarkers. Univariate and multivariate statistical analyses will be used for hypothesis testing and identification of important biomarkers. In summary, this study aims to delineate the pathophysiology of RHD and degenerative AS using multiparametric CMR imaging. In addition to discover novel biomarkers and explore the pathomechanisms associated with RHD and AS through high-throughput profiling of the tissue and blood proteome and metabolome and provide a proof of concept of the suitability of using cadaveric tissues as controls for cardiovascular disease studies.

Hematological and renal toxicity in mice after three cycles of high activity [177Lu]Lu-PSMA-617 with or without human α1-microglobulin

Radioligand therapy with [177Lu]Lu-PSMA-617 can be used to prolong life and reduce tumor burden in terminally ill castration resistant prostate cancer patients. Still, accumulation in healthy tissue limits the activity that can be administered. Therefore, fractionated therapy is used to lower toxicity. However, there might be a need to reduce toxicity even further with e.g. radioprotectors. The aim of this study was to (i). establish a preclinical mouse model with fractionated high activity therapy of three consecutive doses of 200 MBq [177Lu]Lu-PSMA-617 in which we aimed to (ii). achieve measurable hematotoxicity and nephrotoxicity and to (iii). analyze the potential protective effect of co-injecting recombinant α1-microglobulin (rA1M), a human antioxidant previously shown to have radioprotective effects. In both groups, three cycles resulted in increased albuminuria for each cycle, with large individual variation. Another marker of kidney injury, serum blood urea nitrogen (BUN), was only significantly increased compared to control animals after the third cycle. The number of white and red blood cells decreased significantly and did not reach the levels of control animals during the experiment. rA1M did reduce absorbed dose to kidney but did not show significant protection here, but future studies are warranted due to the recent clinical studies showing a significant renoprotective effect in patients.

Surgical Approach to Urethral Diverticulum and Urethrovaginal Fistula With Mesh Erosion.

This video illustrates a rare surgical case involving a urethral diverticulum, urethrovaginal fistula, and mesh erosion. We present a 58-year-old patient attending a tertiary care center with a suspected urethrovaginal fistula. Her concerns included stress urinary incontinence (SUI), recurrent urinary tract infection, and vaginal pain. The surgical history was notable for the placement of two different mesh slings during the same procedure to treat SUI. Preoperative evaluation and findings are illustrated in detail. The video uses a high-definition surgical camera to emphasize the initial intraoperative evaluation with localization of the fistula and diverticulum. We then demonstrate the approach to the dissection with the goal of ensuring complete resection of the diverticulum, fistula, and mesh, while preserving healthy tissue for subsequent closure. The utilization of unique and specialized tools for each portion of the procedure is also illustrated. A layered vaginal closure, including a Martius flap, is created to prevent recurrence. The surgery was accomplished without complications. To our knowledge, concomitant findings of a urethral diverticulum, urethrovaginal fistula, and mesh erosion are unique in the literature. We postulate that this triad could have resulted from the mesh burden in this particular patient.

Characterization of a novel proton-CT scanner based on Silicon and LaBr3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$_3$$\\end{document}(Ce) detectors

Treatment planning systems at proton-therapy centres entirely use X-ray computed tomography (CT) as primary imaging technique to infer the proton treatment doses to tumour and healthy tissues. However, proton stopping powers in the body, as derived from X-ray images, suffer from important proton-range uncertainties. In order to reduce this uncertainty in range, one could use proton-CT images instead. The main goal of this work is to test the capabilities of a newly-developed proton-CT scanner, based on the use of a set of tracking detectors and a high energy resolution scintillator for the residual energy of the protons. Different custom-made phantoms were positioned at the field of view of the scanner and were irradiated with protons at the CCB proton-therapy center in Krakow. We measured with the phantoms at different angles and produced sinograms that were used to obtain reconstructed images by Filtered Back-Projection. The obtained images were used to determine the capabilities of our scanner in terms of spatial resolution and proton Relative Stopping Power (RSP) mapping and validate its use as proton-CT scanner. The results show that the scanner can produce medium-high quality images, with spatial resolution better than 2 mm in radiography, below 3 mm in tomography and resolving power in the RSP comparable to other state-of-the-art pCT scanners.

Osseoscopy-assisted core decompression and debridement in the treatment of avascular necrosis of the femoral head.

Core decompression of the femoral head is a standard surgical procedure used in the early stages of the femoral head avascular necrosis (AVN) (Steinberg I to III). This study aimed to determine whether the advantages of osseoscopy-assisted core decompression using a standard arthroscopic set up in the early stages of AVN of the femoral head. Twelve hips of 12 patients who underwent osseoscopy-assisted core decompression and debridement with the diagnosis of AVN of the femoral head were reviewed between 2019 and 2021. The etiology was idiopathic in 2 patients; ten had a history of steroid use. The preoperative and postoperative first month Harris Hip Score (HHS) and visual analogue scale (VAS) were recorded. Standard X-rays, computerized tomography, and magnetic resonance imaging (MRI) were noted at preoperatively and sixth month follow-ups. In a 1-year follow-up, X-rays and MRIs were reviewed. All patients significantly improved in the VAS and HHS after the osseoscopy-assisted core decompression (P = .002). Two of the 12 patients with an initial stage of Steinberg IIC and IIB and one with Steinberg IA had a progressive femoral collapse and, therefore, had a total hip replacement at the end of the follow-up. Nine patients (75%) had satisfactory functional and radiological results in 1-year of follow-up. However, 3 patients (25%) culminated in total hip arthroplasty in a 1-year follow-up. Using an arthroscopic set up during osseoscopy-assisted core decompression surgery of the femoral head AVN has the benefits of direct visualization and accurate debridement of the involved area. The osseoscopy-assisted core decompression technique avoids excessive debridement of the healthy bone tissue adjacent to the necrotic area.

Therapeutic Potential of Chlorogenic Acid in Chemoresistance and Chemoprotection in Cancer Treatment

Chemotherapeutic drugs are indispensable in cancer treatment, but their effectiveness is often lessened because of non-selective toxicity to healthy tissues, which triggers inflammatory pathways that are harmful to vital organs. In addition, tumors’ resistance to drugs causes failures in treatment. Chlorogenic acid (5-caffeoylquinic acid, CGA), found in plants and vegetables, is promising in anticancer mechanisms. In vitro and animal studies have indicated that CGA can overcome resistance to conventional chemotherapeutics and alleviate chemotherapy-induced toxicity by scavenging free radicals effectively. This review is a summary of current information about CGA, including its natural sources, biosynthesis, metabolism, toxicology, role in combatting chemoresistance, and protective effects against chemotherapy-induced toxicity. It also emphasizes the potential of CGA as a pharmacological adjuvant in cancer treatment with drugs such as 5-fluorouracil, cisplatin, oxaliplatin, doxorubicin, regorafenib, and radiotherapy. By analyzing more than 140 papers from PubMed, Google Scholar, and SciFinder, we hope to find the therapeutic potential of CGA in improving cancer therapy.

Biofilms and core pathogens shape the tumor microenvironment and immune phenotype in colorectal cancer

ABSTRACT Extensive research has explored the role of gut microbiota in colorectal cancer (CRC). Nonetheless, metatranscriptomic studies investigating the in situ functional implications of host-microbe interactions in CRC are scarce. Therefore, we characterized the influence of CRC core pathogens and biofilms on the tumor microenvironment (TME) in 40 CRC, paired normal, and healthy tissue biopsies using fluorescence in situ hybridization (FISH) and dual-RNA sequencing. FISH revealed that Fusobacterium spp. was associated with increased bacterial biomass and inflammatory response in CRC samples. Dual-RNA sequencing demonstrated increased expression of pro-inflammatory cytokines, defensins, matrix-metalloproteases, and immunomodulatory factors in CRC samples with high bacterial activity. In addition, bacterial activity correlated with the infiltration of several immune cell subtypes, including M2 macrophages and regulatory T-cells in CRC samples. Specifically, Bacteroides fragilis and Fusobacterium nucleatum correlated with the infiltration of neutrophils and CD4+ T-cells, respectively. The collective bacterial activity/biomass appeared to exert a more significant influence on the TME than core pathogens, underscoring the intricate interplay between gut microbiota and CRC. These results emphasize how biofilms and core pathogens shape the immune phenotype and TME in CRC while highlighting the need to extend the bacterial scope beyond CRC pathogens to advance our understanding and identify treatment targets.

Model predictive control (MPC) applied to a simplified model, magnetic nanoparticle hyperthermia (MNPH) treatment process

Magnetic nanoparticle hyperthermia (MNPH) has emerged as a promising cancer treatment that complements conventional ionizing radiation and chemotherapy. MNPH involves injecting iron-oxide nanoparticles into the tumor and exposing it to an alternating magnetic field (AMF). Iron oxide nanoparticles produce heat when exposed to radiofrequency AMF due to hysteresis loss. Minimizing the non-specific heating in human tissues caused by exposure to AMF is crucial. A pulse-width-modulated AMF has been shown to minimize eddy-current heating in superficial tissues. This project developed a control strategy based on a simplified mathematical model in MATLAB SIMULINK® to minimize eddy current heating while maintaining a therapeutic temperature in the tumor. A minimum tumor temperature of 43 [°C] is required for at least 30 [min] for effective hyperthermia, while maintaining the surrounding healthy tissues below 39 [°C]. A model predictive control (MPC) algorithm was used to reach the target temperature within approximately 100 [s]. As a constrained MPC approach, a maximum AMF amplitude of 36 [kA/m] and increment of 5 [kA/m/s] were applied. MPC utilized the AMF amplitude as an input and incorporated the open-loop response of the eddy current heating in its dynamic matrix. A conventional proportional integral (PI) controller was implemented and compared with the MPC performance. The results showed that MPC had a faster response (30 [s]) with minimal overshoot (1.4 [%]) than PI controller (115 [s] and 5.7 [%]) response. In addition, the MPC method performed better than the structured PI controller in its ability to handle constraints and changes in process parameters.

Scuphr: A probabilistic framework for cell lineage tree reconstruction

Cell lineage tree reconstruction methods are developed for various tasks, such as investigating the development, differentiation, and cancer progression. Single-cell sequencing technologies enable more thorough analysis with higher resolution. We present Scuphr, a distance-based cell lineage tree reconstruction method using bulk and single-cell DNA sequencing data from healthy tissues. Common challenges of single-cell DNA sequencing, such as allelic dropouts and amplification errors, are included in Scuphr. Scuphr computes the distance between cell pairs and reconstructs the lineage tree using the neighbor-joining algorithm. With its embarrassingly parallel design, Scuphr can do faster analysis than the state-of-the-art methods while obtaining better accuracy. The method’s robustness is investigated using various synthetic datasets and a biological dataset of 18 cells.

Study of gamma, neutron, and proton interaction parameters of some immunotherapy drugs using EpiXs, NGCal, and PSTAR software

Abstract In proton therapy, the protons are used to destroy the cancer cells efficiently at the Bragg peak without much damage to normal cells. The protons can also produce neutrons, protons, and high-energy gamma rays through nuclear reactions with cancerous and healthy tissues as well as with beamline components. The effective observed dose in the therapy is enhanced due to the interaction of nuclear particles with cancerous tissues. Such nuclear particles can have several effects on drugs used in immunotherapy, such as immunotherapy in combination with proton therapy, which has been used to treat cancer. In the present investigations, the gamma, neutron, and protons interaction parameters of some immunotherapy drugs, such as dostarlimab, atezolizumab, ipilimumab, nivolumab, and pembrolizumab, are determined by using EpiXs, NGCal, and PSTAR software. It is found that the EBF and EABF for all selected immunotherapy drugs increase with increasing penetration depth, peaking at 100 keV. The peaking is more symmetric at a higher penetration depth of 40 mfp than at a lower one of 1 mfp. At lower energies of gamma photons, the EBF values increase exponentially, and at higher energies, they increase linearly with increasing penetration depth for all selected drugs. Mass attenuation factors are slightly higher for thermal neutrons than for fast neutrons for selected immunotherapeutic drugs, indicating that thermal neutrons more actively participate in these drugs than fast neutrons. The mass attenuation factor for both fast and thermal neutrons increases with increasing weight percentages of hydrogen and is found to be higher for thermal neutrons. This is the first study in the literature to investigate the radiation interaction parameters for immunotherapy drugs, and it is helpful in radiation therapy and dosimetry.

A preliminary in vivo and in vitro study of endothelial cell pyroptosis in the periodontal inflammatory environment

Objective: To observe whether endothelial cells undergo pyroptosis in the inflammatory periodontal environment by using a model in vivo and in vitro, providing an experimental basis for indepth understanding of the underlying pathogenesis of periodontitis. Methods: According to the classification of periodontal diseases of 2018, gingival tissues were collected from periodontally healthy subjects and patients with stage Ⅲ-Ⅳ, grade C periodontitis, who presented Department of Oral and Maxillofacial Surgery and Department of Periodontology, School of Stomatology, The Fourth Military Medical University from April to May 2022. Immunohistochemical staining was performed to detect the expression level and distribution of gasdermin D (GSDMD), a hallmark protein of cell pyroptosis, in gingival tissues. Periodontitis models were established in each group by ligating the maxillary second molar teeth of three mice for 2 weeks (ligation group). The alveolar bone resorption was determined by micro-CT (mice without ligation treatment were used as the control group), and the colocalization of GSDMD and CD31 were quantitatively analyzed by immunofluorescence staining in gingival tissues of healthy and inflammatory mice. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and treated with lipopolysaccharide (LPS) of Porphyromonas gingivalis (Pg) combined with adenosine triphosphate (ATP) at various concentrations of 0.5, 1.0, 2.5, 5.0, and 10.0 mg/L, respectively, and the 0 mg/L group was set as the control group at the same time. Scanning electron microscopy was used to observe the morphology of HUVECs. Western blotting was used to detect the expression of gasdermin D-N terminal domains (GSDMD-N) protein and immunofluorescence cell staining was used to detect the expression and distribution of GSDMD. Cell counting kit-8 (CCK-8) was used to detect the proliferative ability of HUVECs, and propidium iodide (PI) staining was used to detect the integrity of cell membrane of HUVECs. Results: Immunohistochemistry showed that GSDMD in gingival tissues of periodontitis was mainly distributed around blood vessels and its expression level was higher than that in healthy tissues. Micro-CT showed that alveolar bone resorption around the maxillary second molar significantly increased in ligation group mice compared with control subjects (t=8.88, P<0.001). Immunofluorescence staining showed significant colocalization of GSDMD with CD31 in the gingival vascular endothelial cells in mice of ligation group. The results of scanning electron microscopy showed that there were pores of different sizes, the typical morphology of pyroptosis, on HUVECs cell membranes in the inflammatory environment simulated by ATP combined with different concentrations of LPS, and 2.5 mg/L group showed the most dilated and fused pores on cell membranes, with the cells tended to lyse and die. Western blotting showed that the expression of GSDMD-N, the hallmark protein of cell pyroptosis, was significantly higher in 2.5 and 5.0 mg/L groups than that in the control group (F=3.86, P<0.01). Immunofluorescence cell staining showed that the average fluorescence intensity of GSDMD in 2.5 mg/L group elevated the most significantly in comparison with that in the control group (F=35.25, P<0.001). The CCK-8 proliferation assay showed that compared to the control group (1.00±0.02), 0.5 mg/L (0.52±0.07), 1.0 mg/L (0.57±0.10), 2.5 mg/L (0.58±0.04), 5.0 mg/L (0.55±0.04), 10.0 mg/L (0.61±0.03) groups inhibited cell proliferation (F=39.95, P<0.001). PI staining showed that the proportion of positive stained cells was highest [(56.07±3.22)%] in 2.5 mg/L group (F=88.24, P<0.001). Conclusions: Endothelial cells undergo significant pyroptosis in both in vivo and in vitro periodontal inflammatory environments, suggesting that endothelial cell pyroptosis may be an important pathogenic factor contributing to the pathogenesis of periodontitis.

A high-resolution large-area detector for quality assurance in radiotherapy

Hadron therapy is an advanced radiation modality for treating cancer, which currently uses protons and carbon ions. Hadrons allow for a highly conformal dose distribution to the tumour, minimising the detrimental side-effects due to radiation received by healthy tissues. Treatment with hadrons requires sub-millimetre spatial resolution and high dosimetric accuracy. This paper discusses the design, fabrication and performance tests of a detector based on Gas Electron Multipliers (GEM) coupled to a matrix of thin-film transistors (TFT), with an active area of 60 × 80 mm2 and 200 ppi resolution. The experimental results show that this novel detector is able to detect low-energy (40 kVp X-rays), high-energy (6 MeV) photons used in conventional radiation therapy and protons and carbon ions of clinical energies used in hadron therapy. The GEM-TFT is a compact, fully scalable, radiation-hard detector that measures secondary electrons produced by the GEMs with sub-millimetre spatial resolution and a linear response for proton currents from 18 pA to 0.7 nA. Correcting known detector defects may aid in future studies on dose uniformity, LET dependence, and different gas mixture evaluation, improving the accuracy of QA in radiotherapy.

Eosinophil Specialization Is Regulated by Exposure to the Esophageal Epithelial Microenvironment

Abstract Distinct subsets of eosinophils are reported in inflammatory and healthy tissues, yet the functions of uniquely specialized eosinophils and the signals that elicit them, particularly in eosinophilic esophagitis (EoE), are not well understood. Herein, we report an ex-vivo system wherein freshly isolated human eosinophils were cocultured with esophageal epithelial cells and disease-relevant pro-inflammatory (IL-13) or pro-fibrotic (TGF-β) cytokines. Compared with untreated cocultures, IL-13 increased expression of CD69 on eosinophils, whereas TGF-β increased expression of CD81, CD62L, and CD25. Eosinophils from IL-13–treated cocultures demonstrated increased secretion of GRO-α, IL-8, and M-CSF and also generated increased extracellular peroxidase activity following activation. Eosinophils from TGF-β–treated cocultures secreted increased IL-6 and exhibited increased chemotactic response to CCL11 compared with eosinophils from untreated or IL-13—treated coculture conditions. When eosinophils from TGF-β–treated cocultures were cultured with fibroblasts, they upregulated SERPINE1 expression and fibronectin secretion by fibroblasts compared with eosinophils that were cultured with GM-CSF, alone. Translational studies revealed that CD62L was heterogeneously expressed by eosinophils in patient biopsies. Our results demonstrate that disease-relevant pro-inflammatory and pro-fibrotic signals present in the esophagus of EoE patients cause distinct profiles of eosinophil activation and gene expression.

Discovery and characterization of a novel pathogen Erwinia pyri sp. nov. associated with pear dieback: taxonomic insights and genomic analysis

In 2022, a novel disease similar to pear fire blight was found in a pear orchard in Zhangye City, Gansu Province, China. The disease mainly damages the branches, leaves, and fruits of the plant. To identify the pathogen, tissue isolation and pathogenicity testing (inoculating the potential pathogen on healthy plant tissues) were conducted. Furthermore, a comprehensive analysis encompassing the pathogen’s morphological, physiological, and biochemical characteristics and whole-genome sequencing was conducted. The results showed that among the eight isolates, the symptoms on the detached leaves and fruits inoculated with isolate DE2 were identical to those observed in the field. Verifying Koch’s postulates confirmed that DE2 was the pathogenic bacterium that causes the disease. Based on a 16S rRNA phylogenetic tree, isolate DE2 belongs to the genus Erwinia. Biolog and API 20E results also indicated that isolate DE2 is an undescribed species of Erwinia. Isolate DE2 was negative for oxidase. Subsequently, the complete genome sequence of isolate DE2 was determined and compared to the complete genome sequences of 29 other Erwinia species based on digital DNA–DNA hybridization (dDDH) and average nucleotide identity (ANI) analyses. The ANI and dDDH values between strain DE2 and Erwinia species were both below the species thresholds (ANI &amp;lt; 95–96%, dDDH&amp;lt;70%), suggesting that isolate DE2 is a new species of Erwinia. We will temporarily name strain DE2 as Erwinia pyri sp. nov. There were 548 predicted virulence factors in the genome of strain DE2, comprising 534 on the chromosome and 5 in the plasmids. The whole genome sequence of strain DE2 has been submitted to the NCBI database (ASM3075845v1) with accession number GCA_030758455.1. The strain DE2 has been preserved at the China Center for Type Culture Collection (CCTCC) under the deposit number CCTCC AB 2024080. This study represents the initial report of a potentially new bacterial species in the genus Erwinia that causes a novel pear dieback disease. The findings provide a valuable strain resource for the study of the genus Erwinia and establish a robust theoretical foundation for the prevention and control of emerging pear dieback diseases.

A Novel Approach for Treating Lipomas: Percutaneous Microwave Ablation Combined with Liposuction.

Lipomas, benign adipose tissue tumors, are a common occurrence but currently, the options for their treatment are limited, with surgical excision being the most frequently used management pathway. This scenario can often lead to unsatisfactory cosmetic results and significant patient discomfort. This paper introduces a novel technique, percutaneous microwave ablation with liposuction, to address these challenges. The innovative procedure aims to enhance patient satisfaction, minimize post-operative discomfort, and improve aesthetic outcomes. The technique involves two key steps: (1) the application of percutaneous microwave ablation to selectively disrupt the lipoma cells, followed by (2) a targeted liposuction procedure to remove the ablated lipoma tissue. Our approach optimizes the removal of the lipoma and preserves the surrounding healthy tissue, reducing the risk of local recurrence and improving the cosmetic result. The use of preoperative ultrasound imaging allows for precise localization and delineation of the lipoma, aiding in the planning and execution of the procedure. This novel approach to lipoma treatment is reliable, associated with minimal morbidity, and consistently yields effective results. Additionally, it provides a new perspective on lipoma management, potentially changing the paradigm of current treatment approaches.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .