bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential use of Fas ligand and perforin cytotoxic pathways by donor T cells in graft-versus-host disease and graft-versus-leukemia effect
Authors: Schmaltz Cornelius , Alpdogan Onder , Horndasch Kirsten J. , Muriglan Stephanie J. , Kappel Barry J. , Teshima Takanori , Ferrara James L. M. , Burakoff Steven J. , van den Brink Marcel R. M. 
Published: July 2002

AbstractIn allogeneic bone marrow transplantation (BMT) donor T cells are primarily responsible for antihost activity, resulting in graft-versus-host disease (GVHD), and for antileukemia activity, resulting in the graft-versus-leukemia (GVL) effect. The relative contributions of the Fas ligand (FasL) and perforin cytotoxic pathways in GVHD and GVL activity were studied by using FasL-defective or perforin-deficient donor T cells in murine parent → F1 models for allogeneic bone marrow transplantation. It was found that FasL-defective B6.gld donor T cells display diminished GVHD activity but have intact GVL activity. In contrast, perforin-deficient B6.pfp−/− donor T cells have intact GVHD activity but display diminished GVL activity. Splenic T cells from recipients of B6.gld or B6.pfp−/− T cells had identical proliferative and cytokine responses to host antigens; however, splenic T cells from recipients of B6.pfp−/− T cells had no cytolytic activity against leukemia cells in a cytotoxicity assay. In experiments with selected CD4+ or CD8+ donor T cells, the FasL pathway was important for GVHD activity by both CD4+ and CD8+ T cells, whereas the perforin pathway was required for CD8-mediated GVL activity. These data demonstrate in a murine model for allogeneic bone marrow transplantation that donor T cells mediate GVHD activity primarily through the FasL effector pathway and GVL activity through the perforin pathway. This suggests that donor T cells make differential use of cytolytic pathways and that the specific blockade of one cytotoxic pathway may be used to prevent GVHD without interfering with GVL activity.
Prognostic factors and response to fludarabine therapy in patients with Waldenström macroglobulinemia: results of United States intergroup trial (Southwest Oncology Group S9003)
Authors: Dhodapkar Madhav V. , Jacobson Joth L. , Gertz Morie A. , Rivkin Saul E. , Roodman G. David , Tuscano Joseph M. , Shurafa Muhammad , Kyle Robert A. , Crowley John J. , Barlogie Bart 
Published: July 2002

AbstractCurrent information on Waldenström macroglobulinemia (WM) is based on retrospective or single-institution studies of patients requiring therapy. Between 1992 and 1998, 231 patients with WM were enrolled in a prospective observational multicenter clinical trial. Of these, 182 patients with symptomatic or progressive disease were treated with 4 to 8 cycles of therapy with a purine nucleoside analogue, fludarabine (FAMP; 30 mg/m2 of body-surface area daily for 5 days every 28 days). A serum β2-microglobulin (β2M) level below 3 mg/L and a hemoglobin level of at least 120 g/L (12 g/dL) at presentation predicted a lower likelihood of requiring therapy. The overall rate of response to FAMP therapy was 36% (95% confidence interval, 29%-44%), with 2% complete remissions. Patients who were 70 years old or older had a substantially lower likelihood of response (odds ratio, 0.34; P = .004) than younger patients. On multivariate analysis, a serum β2M level of 3 mg/L or higher, hemoglobin level below 120 g/L, and serum IgM level below 40 g/L [4 g/dL] were significant adverse prognostic factors for survival. We developed a simple staging system for WM by using these variables and identified 4 distinct subsets of patients with estimated 5-year overall survival rates of 87%, 64%, 53%, and 22%, and 5-year progression-free survival rates of 83%, 55%, 33%, and 12%. Prognosis in WM is highly variable and serum β2M was the dominant predictor of a need for therapy and of survival. FAMP has activity against WM. Our staging system may provide guidance for a risk-based approach to the treatment of WM.
Engraftment of DLA-haploidentical marrow with ex vivo expanded, retrovirally transduced cytotoxic T lymphocytes
Authors: Georges George E. , Storb Rainer , Bruno Benedetto , Brodie Scott J. , Thompson Jennifer D. , Taranova Anna G. , Zaucha J. Maciej , Little Marie-Térèse , Zellmer Eustacia , Moore Peter F. , Gooley Theodore , Sale George , Kiem Hans-Peter , Sandmaier Brenda M. , Lyons Russette M. , Nash Richard A. 
Published: July 2002

AbstractGenetically modified donor T cells with an inducible “suicide” gene have the potential to improve the safety and availability of allogeneic hematopoietic stem cell transplantation by enhancing engraftment and permitting control of graft-versus-host disease (GVHD). However, several clinical studies of gene-modified T cells have shown limited to no in vivo function of the ex vivo expanded T cells. Using the well-established dog model of allogeneic marrow transplantation, the question was asked if retrovirally transduced, donor derived, ex vivo expanded cytotoxic T lymphocytes (CTLs) that are recipient specific could enhance engraftment of dog leukocyte antigen (DLA)–haploidentical marrow following a single dose of 9.2 Gy total body irradiation and no postgrafting immunosuppression. In this setting, only 4 of 11 control recipients of DLA-haploidentical marrow without added CTLs engrafted. CTLs did not enhance engraftment of CD34+ selected peripheral blood stem cells. However, recipient-specific CTLs enhanced engraftment of DLA-haploidentical marrow in 9 of 11 evaluable recipients (P = .049). All dogs that engrafted developed multiorgan GVHD. To facilitate in vivo tracking, 8 dogs received CTLs transduced with a retroviral vector encoding green fluorescent protein (GFP) and neomycin phosphotransferase (neo). Recipients that engrafted had sharp increases in the numbers of circulating GFP+ CTLs on days +5 to +6 after transplantation. GFP+ CTLs isolated from blood were capable of recipient-specific lysis. At necropsy, up to 7.1% of CD3+ cells in tissues were GFP+ and polymerase chain reaction in situ hybridization for neoshowed infiltration of transduced CTLs in GVHD-affected organs. These results show that ex vivo expanded, transduced T cells maintained in vivo function and enhanced marrow engraftment.
Reduction in drug-induced DNA double-strand breaks associated with β1 integrin–mediated adhesion correlates with drug resistance in U937 cells
Authors: Hazlehurst Lori A. , Valkov Nikola , Wisner Lee , Storey Jonathan A. , Boulware David , Sullivan Daniel M. , Dalton William S. 
Published: July 2002

Abstract
We previously showed that adhesion of myeloma cells to fibronectin (FN) by means of β1 integrins causes resistance to certain cytotoxic drugs. The study described here found that adhesion of U937 human histiocytic lymphoma cells to FN provides a survival advantage with respect to damage induced by the topoisomerase (topo) II inhibitors mitoxantrone, doxorubicin, and etoposide. Apoptosis induced by a topo II inhibitor is thought to be initiated by DNA damage. The neutral comet assay was used to determine whether initial drug-induced DNA damage correlated with cellular-adhesion–mediated drug resistance. Cellular adhesion by means of β1 integrins resulted in a 40% to 60% reduction in mitoxantrone- and etoposide-induced DNA double-strand breaks. When the mechanisms regulating the initial drug-induced DNA damage were examined, a β1 integrin–mediated reduction in drug-induced DNA double-strand breaks was found to correlate with reduced topo II activity and decreased salt-extractable nuclear topo IIβ protein levels. Confocal studies showed changes in the nuclear localization of topo IIβ; however, alterations in the nuclear-to-cytoplasmic ratio of topo IIβ in FN-adhered cells were not significantly different. Furthermore, after a high level of salt extraction of nuclear proteins, higher levels of topo IIβ–associated DNA binding were observed in FN-adhered cells than in cells in suspension. Together, these data suggest that topo IIβ is more tightly bound to the nucleus of FN-adhered cells. Thus, FN adhesion by means of β1 integrins appears to protect U937 cells from initial drug-induced DNA damage by reducing topo II activity secondarily to alterations in the nuclear distribution of topo IIβ.
Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients
Authors: Onida Francesco , Kantarjian Hagop M. , Smith Terry L. , Ball Greg , Keating Michael J. , Estey Elihu H. , Glassman Armand B. , Albitar Maher , Kwari Monica I. , Beran Miloslav 
Published: July 2002

AbstractChronic myelomonocytic leukemia (CMML) is a hematologic malignancy characterized by wide heterogeneity of clinical presentation and course. CMML shares myelodysplastic characteristics with features of myeloproliferative disorders. No treatment has proven effective in modifying the natural course of the disease. To improve the prognostic assessment of clinical outcome, the associations of patient and disease characteristics with survival times of 213 patients with CMML was investigated retrospectively. Median survival was 12 months. Univariate analysis identified low hemoglobin level; low platelet count; high white blood cell, monocyte, and lymphocyte counts; presence of circulating immature myeloid cells, high percentage of marrow blasts, low percentage of marrow erythroid cells, abnormal cytogenetics, and high levels of serum lactate dehydrogenase and β2-microglobulin as characteristics associated with shorter survival. Hemoglobin level below 120 g/L (12 g/dL), presence of circulating immature myeloid cells, absolute lymphocyte count above 2.5 × 109/L, and marrow blasts 10% or more were independently associated with shorter survival by multivariate analysis and were used to generate a prognostic score. The model identified 4 subgroups of patients with median survival of 24, 15, 8, and 5 months for low, intermediate-1, intermediate-2, and high risk, respectively. Researchers could not confer objective evidence suggesting that arbitrary divisions of CMML by white blood cell counts into “dysplastic” and “proliferative” categories reflect clinical entities differing in the risk of acute leukemia development, although a trend of shorter survival in patients with leukocytosis was observed. The prognostic model was compared with 6 previously published scoring systems for myelodysplastic syndrome/CMML. The reported results should provide an improved assessment of prognosis in CMML.
Extragonadal Germ Cell Tumors of the Mediastinum and Retroperitoneum: Results From an International Analysis
Authors: Bokemeyer Carsten , Nichols Craig R. , Droz Jean-P. , Schmoll Hans-J. , Horwich Alan , Gerl Arthur , Fossa Sophie D. , Beyer Jörg , Pont Jörg , Kanz Lothar , Einhorn Lawrence , Hartmann Jörg T. 
Published: July 2002

PURPOSE: To characterize the clinical and biologic features of extragonadal germ cell tumor (EGCT) and to determine the overall outcome with currently available treatment strategies. PATIENTS AND METHODS: Of an unselected population of 635 consecutive patients treated from 1975 through 1996 at 11 cancer centers, 341 patients (54%) had primary mediastinal EGCT, and 283 patients (45%) had retroperitoneal EGCT. Five hundred twenty-four patients (83%) had a nonseminomatous germ cell tumor (GCT), and 104 patients (16%) had a seminomatous histology. RESULTS: After platinum-based induction chemotherapy with or without secondary surgery, 141 patients (49%) with mediastinal nonseminomas (median follow-up, 19 months; range, 1 to 178 months) and 144 patients (63%) with retroperitoneal nonseminoma (median follow-up, 29 months; range, 1 to 203 months) are alive (P = .0006). In contrast, the overall survival rate for patients with a seminomatous EGCT is 88%, with no difference between patients with mediastinal or retroperitoneal tumor location (median follow-up, 49 months; range, 4 to 193 months; respective 70 months; range, 1 to 211 months). A significantly lower progression-free survival rate was found in seminoma patients treated with initial radiotherapy alone compared with chemotherapy. Nonseminomatous histology, presence of nonpulmonary visceral metastases, primary mediastinal GCT location, and elevated beta-human chorionic gonadotropin were independent prognostic factors for shorter survival. Hematologic malignancies (n = 17) occurred without exception in patients with primary mediastinal nonseminoma. Sixteen patients developed a metachronous testicular cancer despite the use of platinum-based chemotherapy. CONCLUSION: Whereas patients with pure seminomatous EGCT histology have a long-term chance of cure of almost 90% irrespective of the primary tumor site, 45% of patients with mediastinal nonseminomas are alive at 5 years. This outcome is clearly inferior compared with patients with nonseminomatous retroperitoneal primary tumors.
Axial Spondyloarthritis
Authors: Bittar Mohamad , Deodhar Atul 
Published: December 2024

ImportanceAxial spondyloarthritis is an immune-mediated inflammatory condition involving the sacroiliac joints, spine, and peripheral joints. It affects approximately 1% of adults in the US and is associated with impaired physical function and reduced quality of life.ObservationsInflammatory chronic back pain characterized by gradual onset starting before age 45 years, prolonged morning stiffness, improvement with exercise, and lack of improvement with rest is the most common symptom of axial spondyloarthritis and affects more than 80% of patients. Patients with axial spondyloarthritis may also have inflammatory arthritis in large peripheral joints (most commonly knees) in an oligoarticular, asymmetric fashion; inflammation at tendon insertions (enthesitis); inflammatory eye disease (uveitis); psoriasis; and inflammatory bowel disease. The pathogenesis of axial spondyloarthritis may involve genetic predisposition, gut microbial dysbiosis, and entheseal trauma, with immune cell infiltration of the sacroiliac joints and entheseal insertion areas in the spine. There are currently no diagnostic criteria for axial spondyloarthritis. The diagnosis, often delayed 6 to 8 years after symptom onset, is based on history (ie, inflammatory back pain [sensitivity, 74%-81%; specificity, 25%-44%]), laboratory findings (human leukocyte antigen B27–positive [sensitivity, 50%; specificity, 90%] and elevated C-reactive protein level [sensitivity, 35%; specificity, 91%]), and imaging findings consisting of sacroiliitis on plain radiography (sensitivity, 66%; specificity, 68%) or magnetic resonance imaging (sensitivity, 78%; specificity, 88%). First-line treatments are physical therapy and nonsteroidal anti-inflammatory drugs (NSAIDs). However, less than 25% of patients achieve complete symptom control with NSAIDs. Approximately 75% of patients require biologic drugs (tumor necrosis factor inhibitors [anti-TNF agents], interleukin 17 inhibitors [anti–IL-17 agents]) or targeted synthetic disease-modifying antirheumatic agents (Janus kinase [JAK] inhibitors) to reduce symptoms, prevent structural damage, and improve quality of life. Clinical trials reported that anti-TNF agents significantly improved ASAS20 (measure of pain, function, and inflammation) in 58% to 64% of patients compared with 19% to 38% for placebo. Similar outcomes were attained with anti–IL-17 agents (48%-61%, vs 18%-29% with placebo) and JAK inhibitors (52%-56%, vs 26%-29% with placebo). Anti-TNF agents, anti–IL-17 agents, and JAK inhibitors have been associated with reduced radiographic progression of axial spondyloarthritis.ConclusionsAxial spondyloarthritis predominantly affects the sacroiliac joints and spine but is also associated with extraskeletal manifestations such as uveitis, psoriasis, and inflammatory bowel disease. Physical therapy and NSAIDs are first-line treatments, but most patients require therapy with biologics (anti-TNF or anti–IL-17 agents) or JAK inhibitors to achieve improvement in signs and symptoms, inflammation control, and reduced progression of structural damage.
Robust Optimal Consensus Control for Nonlinear Multi‐agent Systems: Two Hybrid Dynamic Event‐Triggered‐Based Approach
Authors: Zou Haoming , Zhang Guoshan 
Published: December 2024

ABSTRACTIn this paper, the dynamic event‐triggered robust optimal consensus control problem is investigated for nonlinear multi‐agent systems (MASs) with matched and mismatched disturbances via integral sliding mode (ISM) control and the adaptive dynamic programming (ADP) algorithm. First, a dynamic event‐triggered fixed‐time ISM controller is designed to guarantee that the system state converges to the predefined ISM manifold, thereby eliminating the matched disturbances. Next, the consensus control problem is transformed into an optimal control problem by constructing neighborhood error dynamics and a new modified cost function; thus, an event‐triggered‐based coupled Hamilton‐Jacobi‐Bellman equation (HJBE) is established. Then, an ADP‐based single‐critic neural network (NN) is constructed to solve coupled HJBE to obtain the event‐triggered optimal controller, in which the NN weight is updated only at the triggering instants. Through the implementation of these two dynamic event‐triggered mechanisms, resources and controller execution time can be saved. It is proved that the whole closed‐loop system signals are uniformly ultimately bounded by the Lyapunov technique. Finally, two illustrative examples verify the effectiveness and superiority of the proposed control scheme.
Synergistic Strategy toward Enhancing Photosynthesizing Reactive Oxygen Species of Covalent Organic Frameworks
Authors: Zhan Xiaoning , Jin Yucheng , Qu Chen , Liu Heyuan , Jiang Rong , Zhi Qianjun , Qi Dongdong , Wang Kang , Han Bin , Pan Houhe , Jiang Jianzhuang 
Published: December 2024

AbstractPhotocatalytic reactive oxygen species (ROSs) plays an important role in photodynamic therapy and photochemical reactions. However, most reported photocatalysts suffer from insufficient utilization of visible light and low conversion of O2, which requires the development of higher performance catalysts toward practical applications. Herein, a series of porphyrin‐based COFs have been prepared. Comparative experimental and theoretical studies have revealed that the synergistic interaction between the two building blocks can significantly enhance the yields of ROSs by independently accomplishing photon harvesting and oxygen capture with smooth energy transfer between them. Particularly, the 1O2 yield of 3P‐Por‐COF is increased to 1.3 and 3.4 times that of the classical PCN‐224 and porphyrin molecular aggregates. Furthermore, the TOF of 3P‐Por‐COF is as high as 271 h−1 with ≈100% selectivity under red light irradiation in catalyzing thioanisole to methyl phenyl sulfoxide. The conversion and stability of degradation of toluene gas under natural light are also superior to the conventional Fenton catalytic system. The present results should contribute to the design of high‐performance frameworks‐based photocatalysts for ROSs production.
Capillarity‐Assisted 3D Patterning of Liquid Metal
Authors: Gao Ming , Liu Xiaojiang , Fan Jingbo , Gao Jingwen , Zhou Yuning , Zhou Kun 
Published: December 2024

AbstractFlexible electronics with sophisticated 3D architectures enable multidimensional functionalities and multi‐component integration, thus surpassing their 2D counterparts in soft robotics and wearable sensors. Because of its unique metallic and fluidic characteristics, liquid metal (LM) has proven to be an excellent material for fabricating flexible electronics. However, its low viscosity and high surface tension have primarily restricted LM to the creation of 2D‐patterned films on flat surfaces, significantly limiting the complexity and functionality of the resulting flexible devices. In this work, inspired by the capillary‐driven liquid flow in a hierarchical lattice matrix, a 3D patterning method is proposed for LM and extended to the fabrication of porous materials with flexible conductivity. The feasibility and versatility of the proposed method are showcased by fabricating tunable electromagnetic interference shielding materials, programmable 3D circuits, and customizable wearable sensors, highlighting its potential for promoting the development of integrated circuits and wearable electronics.
Molecular Engineering of Ultrabright Biomimetic NanoGhost for Site‐Selective Tumor Imaging and Biodistribution
Authors: Prasad Rajendra , Prerna Kumari , Temgire Mayur , Banerjee Pinaki , Kumari Rohini , Kundu Gopal C , Hattila Deeksha , Mangannavar Chandrashekhar Venkaraddi , Meena Avtar Singh , Gorain Mahadeo , Bellare Jayesh , Chandra Pranjal , Dubey Vikash Kumar 
Published: December 2024

AbstractOptically active ultrabright imaging agents are shown to delineate tumor location with deep tissue visualization in pre noclinical tumor models. NanoGhosts (NGs) particles are reconstructed from the cell membrane and integrated with organic fluorophores to attain ultra‐brightness for solid tumor imaging. Moreover, the integration of amphiphilic and lipophilic molecules reveals structural characteristics of NGs (≈70 nm), which also alter their brightness. Upon intravenous administration (10 mg kg−1 single dose), these ultrabright NGs (778 MESF) enable the high‐resolution of tumor site and real‐time tracking of vital organs with high‐contrast fluorescence signals. Engineered biomimetic NGs demonstrates better resolution and tissue penetration as compared to the clinically approved indocyanine green (ICG). High precision in tumor detection (0.5 h) and strong tumor retention (24 h which is further up to 30th day) without affecting healthy tissues ensure the future scope of NGs in early‐stage cancer imaging. These findings suggest that these NGs mimic the biological characteristics of native cells, enabling them to evade immune clearance and target the solid tumor naturally.
Locally Injectable, ROS‐Scavenging, and ROS‐/pH‐Responsive Polymeric‐Micelles‐Embedded Hydrogels for Precise Minimally Invasive and Long‐Lasting Rheumatoid Therapy
Authors: Liu Xinhua , Chen Xing , Fei Yifan , Zhang Jiamin , Yue Ouyang , Wang Xuechuan , Jiang Huie 
Published: December 2024

AbstractRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovitis, bone‐erosion, and joint‐destruction. Here, we developed a locally injectable, ROS‐scavenging, and ROS‐/pH‐responsive drug‐delivery platform (HC@PTM) by bio‐compositing of aldolizing hyaluronic acid (HA) crosslinked with chitosan (CS), and ROS‐triggered/eliminated micelles (PTM) coupled with the drug methotrexate(MTX). The PTM efficiently eradicate excessive ROS in RA‐joints, precisely triggering drug‐release within inflamed arthritic‐sites and further confer exceptional antioxidant origins to HC@PTM. HC@PTM with outstanding shape‐adaptability and self‐repairing properties effectively conformed to irregular articular cartilage while resisting joint‐induced deformations. Further, the platform's pH‐responsive nature enables on‐demand drug‐release within acidic inflamed synovium, serving as a drug‐reservoir for precise and sustained therapeutic effects. Extensive in vitro and in vivo investigations confirm HC@PTM's ability to induce M2 macrophage polarization, downregulate inflammatory factor expression, and ameliorate the RA‐microenvironment, ultimately achieving synergistic therapeutic outcomes. This study represents significant advancements in precise and long‐term RA‐treatment through a minimally invasive approach, offering potential strategies for novel precision medicine.