Quantum mechanically driven structural-spin glass in two dimensions at finite temperature

In magnetic materials, spins sometimes freeze into spatially disordered glassy states. Glass forming liquids or structural glasses are found very often in three dimensions. However, in two dimensions(2D) it is believed that both spin glass and structural glass can never exist at a finite temperature because they are destroyed by thermal fluctuations. Using a large-scale quantum Monte Carlo simulation, we discover a quantum-mechanically driven 2D glass phase at finite temperatures. Our platform is an Ising spin model with a quantum transverse field on a frustrated triangular lattice. How the present glass phase is formed is understood by the following three steps. First, by the interplay of geometrical frustration and quantum fluctuation, part of the spins spontaneously form an antiferromagnetic honeycomb spin-superstructure. Then, small randomness in the bond interaction works as a relevant perturbation to this superstructure and breaks it up into {\it domains}, making it a structural glass. The glassiness of the superstructure, in turn, generates an emergent random magnetic field acting on the remaining fluctuating spins and freezes them. The shape of domains thus formed depends sensitively on the quenching process, which is one of the characteristic features of glass, originating from a multi-valley free-energy landscape. The present system consists only of {\it a single} bistable Ising degree of freedom, which naturally does not become a structural glass alone nor a spin glass alone. Nevertheless, a glass having both types of nature emerges in the form of coexisting two-component glasses, algebraic structural-glass and long-range ordered spin-glass. This new concept of glass-forming mechanism opens a way to realize functional glasses even in low dimensional systems.Comment: 21pages, 14figure

Shared and Distinct Functions of the Transcription Factors IRF4 and IRF8 in Myeloid Cell Development

Interferon regulatory factor (IRF) 8 and IRF4 are structurally-related, hematopoietic cell-specific transcription factors that cooperatively regulate the differentiation of dendritic cells and B cells. Whilst in myeloid cells IRF8 is known to modulate growth and differentiation, the role of IRF4 is poorly understood. In this study, we show that IRF4 has activities similar to IRF8 in regulating myeloid cell development. The ectopic expression of IRF4 in myeloid progenitor cells in vitro inhibits cell growth, promotes macrophages, but hinders granulocytic cell differentiation. We also show that IRF4 binds to and activates transcription through the IRF-Ets composite sequence (IECS). Furthermore, we demonstrate that Irf8-/-Irf4-/- mice exhibit a more severe chronic myeloid leukemia (CML)-like disease than Irf8-/- mice, involving a disproportionate expansion of granulocytes at the expense of monocytes/macrophages. Irf4-/- mice, however, display no obvious abnormality in myeloid cell development, presumably because IRF4 is expressed at a much lower level than IRF8 in granulocyte-macrophage progenitors. Our results also suggest that IRF8 and IRF4 have not only common but also specific activities in myeloid cells. Since the expression of both the IRF8 and IRF4 genes is downregulated in CML patients, these results may add to our understanding of CML pathogenesis

Diagnostic performance of 18F-FDG PET/CT using point spread function reconstruction on initial staging of rectal cancer: a comparison study with conventional PET/CT and pelvic MRI

Abstract Background Accurate staging is crucial for treatment selection and prognosis prediction in patients with rectal cancer. Point spread function (PSF) reconstruction can improve spatial resolution and signal-to-noise ratio of PET imaging. The aim of this study was to evaluate the effectiveness of 18F-FDG PET/CT with PSF reconstruction for initial staging in rectal cancer compared with conventional PET/CT and pelvic MRI. Methods A total of 59 patients with rectal cancer underwent preoperative 18F-FDG PET/CT and pelvic MRI. The maximum standardized uptake value (SUVmax) and lesion to background (L/B) ratio of possible metastatic lymph nodes, and metabolic tumor volumes (MTVs) of primary tumors were calculated. For N and T (T1-2 vs T3-4) staging, sensitivities, specificities, positive predictive values, negative predictive values, and accuracies were compared between conventional PET/CT [reconstructed with ordered subset expectation maximization (OSEM)], PSF-PET/CT (reconstructed with OSEM+PSF), and pelvic MRI. Histopathologic analysis was the reference standard. Results For N staging, PSF-PET/CT provided higher sensitivity (78.6%) than conventional PET/CT (64.3%), and pelvic MRI (57.1%), and all techniques showed high specificity (PSF-PET: 95.4%, conventional PET: 96.7%, pelvic MRI: 93.5%). SUVmax and L/B ratio were significantly higher in PSF-PET/CT than conventional-PET/CT (p < 0.001). The accuracy for T staging in PSF-PET/CT (69.4%) was not significantly different to conventional PET/CT (73.5%) and pelvic MRI (73.5%). MTVs of PSF and conventional PET showed a significant difference among T stages (p < 0.001), with higher values in advanced stages. In M staging, both PSF and conventional PET/CT diagnosed all distant metastases correctly. Conclusions PSF-PET/CT produced images with higher lesion-to-background contrast than conventional PET/CT, which allowed improved detection of lymph node metastasis without compromising specificity, and showed comparable diagnostic value to MRI in local staging. PSF-PET/CT is likely to have a great value for initial staging in rectal cancer

Non-oncologic incidental uptake on FAPI PET/CT imaging.

Fibroblast-activation protein (FAP) is a serine protease classified in the dipeptidyl peptidase 4 (DPP4) family. FAP is predominantly expressed in activated fibroblasts such as the cancer-associated fibroblasts (CAFs). FAP expression in CAFs is associated with tumor progression and poor prognosis in solid cancers. Recently, radiolabeled FAP inhibitors (FAPI) has been developed, which enables positron emission tomography (PET) imaging of FAP. FAPI PET/CT can provide a higher tumor-to-background ratio (TBR) than 18F-fludeoxyglucose PET/CT in various cancers, and thus has attracted substantial attention. As studies on FAPI PET grow in number and size, incidental findings related to non-oncologic conditions have been increasingly reported. FAPI PET uptake has been reported in various conditions such as benign tumors, fibrotic, granulomatosis, scarring/wound, degenerative diseases, and inflammatory diseases.The knowledge of physiological and non-oncologic causes of FAPI uptake is indispensable for accurate FAPI PET/CT interpretation and can help appropriate management of incidental findings on FAPI PET/CT in patients referred for cancer staging indications. In this review article, we describe for each organ system (Brain, Oral mucosa, Salivary Glands, Thyroid, Lung, Myocardium, Breast, Esophagus, Stomach, Intestine, Liver, Gallbladder, Pancreas, Spleen, Kidney, , Uterus, Bone marrow, Joints, Muscle, Vessels, Lymph nodes), the patterns of physiological FAPI uptake and the main causes of non-oncological uptake reported from the literature with FAPI-02, FAPI-04 and FAPI-46. We also illustrate some examples from our institutional database at UCLA

18F-FDG and 11C-4DST PET/CT for evaluating response to platinum-based doublet chemotherapy in advanced non-small cell lung cancer: a prospective study

Abstract Background 4′-[Methyl-11C] thiothymidine (4DST) PET/CT provides DNA synthesis imaging, which represented a higher correlation with the proliferation in advanced non-small cell lung cancer (NSCLC) than that from imaging with FDG. The aim of this prospective study was to evaluate the potential of 4DST in early therapy monitoring for advanced NSCLC, and to compare the results with those from CT and FDG PET/CT. Results Patients who had been pathologically diagnosed with advanced NSCLC and were scheduled to receive platinum-doublet chemotherapy (PT-DC) were eligible. PET/CT imaging with 4DST and with FDG, and CT were performed at baseline and after 2 cycles of PT-DC (interim). Patients were evaluated semi-quantitatively after the 2 cycles of PT-DC using several PET parameters, response evaluation criteria in solid tumors (RECIST) 1.1 based on CT measurements, European Organization for Research and Treatment of Cancer (EORTC) criteria and PET Response Criteria in Solid Tumors (PERCIST) 1.0 based on PET/CT measurements. Baseline measurement data and metabolic response were compared between patients with progression-free survival (PFS) > 4 months and ≤ 4 months, and PFS and overall survival (OS) were compared between patients with and without metabolic response measured with each of the different parameters, using Kaplan-Meier statistics and log-rank testing. A total of 22 patients were included in this study. For predicting PFS > 4 months and ≤ 4 months, metabolic tumor volume (MTV) of baseline 4DST showed the highest area under the curve (0.73), positive predictive value (80.0%), negative predictive value (66.7%), and accuracy (72.7%) among baseline measurement data and metabolic responses from 4DST PET/CT, FDG PET/CT, and CT. Kaplan-Meier curves and log-rank tests for PFS with MTV of baseline FDG and baseline 4DST, and for OS with MTV of baseline FDG and baseline TLG, and MTV of baseline 4DST revealed significant results. Conclusions MTV of baseline 4DST PET/CT along with MTV of baseline FDG PET/CT represent promising predictors of PFS, and MTV of baseline 4DST PET/CT along with MTV and TLG of baseline FDG PET/CT are possible predictors of OS in patients with advanced NSCLC

Effect of BSA Antigen Sensitization during the Acute Phase of Influenza A Viral Infection on CD11c+ Pulmonary Antigen Presenting Cells

Background: Influenza A viral infection is concerned with induction of asthma. CD11c+ pulmonary antigen presenting cells (APCs) play a central role in sensitization with inhaled antigens during the acute phase of influenza A viral infection and also reside on bronchial epithelium for the long term after sensitization. To investigate the role of CD11c+ pulmonary APCs in the inhaled antigen sensitization during the acute phase of influenza A viral infection, we analyzed their function. Methods: Mice were infected with influenza A virus and were sensitized intranasally with BSA/alum during the acute phase of influenza A viral infection. Expression of surface antigens on CD11c+ pulmonary APCs was analyzed by FACS. Cytokine production from CD11c+ pulmonary APCs, and interaction between CD11c+ pulmonary APCs and naive CD4+ T cells was assessed by ELISA. Ability of antigen presentation by CD11c+ pulmonary APCs was measured by proliferation assay. Results: BSA antigen sensitization during the acute phase of influenza A viral infection induced eosinophil recruitment into the lungs after BSA antigen challenge and moderately increased expression of MHC class II molecules on CD11c+ pulmonary APCs. The interaction between the CD11c+ pulmonary APCs and naive CD4+ T cells secreted large amounts of IL-10. Conclusions: BSA antigen sensitization during the acute phase of influenza A viral infection enhanced IL-10 production from naive CD4+ T cell interaction with CD11c+ pulmonary APCs. The IL-10 secretion evoked Th2 responses in the lungs with downregulation of Th1 responses and was important for the eosinophil recruitment into the lungs after BSA antigen challenge

Efficacy of 4′-[methyl-11C] thiothymidine PET/CT before and after neoadjuvant therapy for predicting therapeutic responses in patients with esophageal cancer: a pilot study

Abstract Background 4′-[Methyl-11C] thiothymidine (4DST) has been introduced as a new cell proliferation imaging PET tracer that incorporates into DNA directly. The aim of this prospective study was to evaluate the efficacy of 4DST PET/CT for predicting responses to neoadjuvant therapy in patients with esophageal cancer comparing with FDG PET/CT. Methods Twenty-six patients who had pre- and post-therapeutic 4DST and FDG PET/CT and underwent esophagectomy following neoadjuvant therapy were used for the analysis. Based on pathological findings, patients were divided into two groups: non-responders and responders. The maximum standardized uptake value (SUVmax), metabolic tumor volume, total lesion glycolysis, and total lesion proliferation of the primary lesion were measured for FDG and 4DST PET. Results The pathological diagnosis revealed 16 responders and 10 non-responders. Non-responders showed significantly higher 4DST post-therapeutic SUVmax (postSUVmax) than responders, whereas FDG postSUVmax showed no statistically significant difference (non-responders vs. responders: 4DST, 6.7 vs. 3.3, p = 0.001; FDG, 6.1 vs. 4.5, p = 0.11). Responders showed a greater reduction in percentage changes of 4DST and FDG SUVmax (ΔSUVmax) from baseline to post-therapeutic PET (non-responders vs. responders: 4DST, − 2.9% vs. − 56.7%, p < 0.001; FDG, − 36.3% vs. − 72.6%, p < 0.001). In ROC analysis, ΔSUVmax and postSUVmax with 4DST provided great diagnostic performance for predicting responses (area under the curve: 4DST ΔSUVmax = 0.92, 4DST postSUVmax = 0.88). Conclusions 4DST PET/CT has a great potential for predicting pathologic response to neoadjuvant therapy in patients with esophageal cancer; it may be slightly superior to that with FDG PET/CT

In Vitro Disease Modeling of Hermansky-Pudlak Syndrome Type 2 Using Human Induced Pluripotent Stem Cell-Derived Alveolar Organoids

iPS細胞を用いて遺伝性間質性肺炎の病態解析に成功 --間質性肺炎の原因究明の足がかりに--. 京都大学プレスリリース. 2019-02-19.It has been challenging to generate in vitro models of alveolar lung diseases, as the stable culture of alveolar type 2 (AT2) cells has been difficult. Methods of generating and expanding AT2 cells derived from induced pluripotent stem cells (iPSCs) have been established and are expected to be applicable to disease modeling. Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by dysfunction of lysosome-related organelles, such as lamellar bodies (LBs), in AT2 cells. From an HPS type 2 (HPS2) patient, we established disease-specific iPSCs (HPS2-iPSCs) and their gene-corrected counterparts. By live cell imaging, the LB dynamics were visualized and altered distribution, enlargement, and impaired secretion of LBs were demonstrated in HPS2-iPSC-derived AT2 cells. These findings provide insight into the AT2 dysfunction in HPS patients and support the potential use of human iPSC-derived AT2 cells for future research on alveolar lung diseases

Associations of quantitative whole-body PSMA-PET metrics with PSA progression status under long-term androgen deprivation therapy in prostate cancer patients: a retrospective single-center study.

PURPOSE: To evaluate whether quantitative whole-body (WB) PSMA-PET metrics under long-term androgen deprivation therapy (ADT) and/or androgen receptor signaling inhibitors (ARSi) are associated with PSA progression. METHODS: Patients who underwent at least 2 68Ga-PSMA-11 PET/CT scans between October 2016 and April 2021 (n = 372) and started a new line of ADT ± ARSi between PET1 and PET2 were retrospectively screened for inclusion. We investigated the association between PCWG3-defined PSA progression status at PET2 and the following PSMA-PET parameters: appearance of new lesions on PET2, ≥ 20% increase in WB-PSMA tumor volume (WB-PSMA-VOL), progression of disease (PD) by RECIP 1.0, and ≥ 30% increase in WB-PSMA-SUVmean from PET1 to PET2. Spearmans rank correlation coefficients and Fishers exact test were used to evaluate the associations. RESULTS: Thirty-five patients were included: 12/35 (34%) were treated with ADT only and 23/35 (66%) with ARSi ± ADT. The median time between PET1 and PET2 was 539&nbsp;days. Changes (%) in median PSA levels, WB-PSMA-SUVmean, and WB-PSMA-VOL from PET1 to PET2 were -86%, -23%, and -86%, respectively. WB-PSMA-VOL ≥ 20%, new lesions, RECIP-PD, and WB-PSMA-SUVmean ≥ 30% were observed in 5/35 (14%), 9/35 (26%), 5/35 (14%), and 4/35 (11%) of the whole cohort, in 3/9 (33%), 7/9 (78%), 3/9 (33%), and 2/9 (22%) of patients with PSA progression at PET2, and in 2/26 (8%), 2/26 (8%), 2/26 (8%), and 2/26 (8%) of patients without PSA progression at PET2 (p = 0.058, p &lt; 0.001, p = 0.058, p = 0.238, respectively). Changes in PSA were correlated to percent changes in WB-PSMA-VOL and WB-PSMA-SUVmean (Spearman ρ: 0.765 and 0.633, respectively; p &lt; 0.001). CONCLUSION: Changes in PSA correlated with changes observed on PSMA-PET, although discordance between PSA and PSMA-PET changes was observed. Further research is necessary to evaluate if PSMA-PET parameters can predict progression-free survival and overall survival and serve as novel endpoints in clinical trials