bluuebunny/crossref_metadata_2025 huggingface dataset:
The familial Mediterranean fever protein, pyrin, associates with microtubules and colocalizes with actin filaments
Authors: Mansfield Elizabeth , Chae Jae Jin , Komarow Hirsh D. , Brotz Tilmann M. , Frucht David M. , Aksentijevich Ivona , Kastner Daniel L.
Published: July 2002

Familial Mediterranean fever (FMF) is a recessive disorder characterized by episodes of fever and intense inflammation. FMF attacks are unique in their sensitivity to the microtubule inhibitor colchicine, contrasted with their refractoriness to the anti-inflammatory effects of glucocorticoids. The FMF gene,MEFV, was recently identified by positional cloning; it is expressed at high levels in granulocytes and monocytes. The present study investigated the subcellular localization of the normal gene product, pyrin. These experiments did not support previously proposed nuclear or Golgi localizations. Instead fluorescence microscopy demonstrated colocalization of full-length GFP- and epitope-tagged pyrin with microtubules; this was markedly accentuated in paclitaxel-treated cells. Moreover, immunoblot analysis of precipitates of stabilized microtubules with recombinant pyrin demonstrated a direct interaction in vitro. Pyrin expression did not affect the stability of microtubules. Deletion constructs showed that the unique N-terminal domain of pyrin is necessary and sufficient for colocalization, whereas disease-associated mutations in the C-terminal B30.2 (rfp) domain did not disrupt this interaction. By phalloidin staining, a colocalization of pyrin with actin was also observed in perinuclear filaments and in peripheral lamellar ruffles. The proposal is made that pyrin regulates inflammatory responses at the level of leukocyte cytoskeletal organization and that the unique therapeutic effect of colchicine in FMF may be dependent on this interaction.
Peripheral blood stem cell allograft rejection mediated by CD4+ T lymphocytes recognizing a single mismatch at HLA-DPβ1*0901
Authors: Fleischhauer Katharina , Zino Elisabetta , Mazzi Benedetta , Sironi Elisabetta , Servida Paolo , Zappone Elisabetta , Benazzi Elena , Bordignon Claudio
Published: July 2002

Little is known about the molecular characteristics of alloantigens recognized by alloreactive T cells mediating hematologic stem cell graft rejection. In particular, it has never been shown that such alloantigens can be encoded by HLA-DPβ alleles. Indeed, matching for HLA-DP antigens is generally not considered to be of functional importance for the outcome of allogeneic bone marrow or peripheral blood stem cell transplantation. In this study, a case of peripheral blood stem cell allograft rejection was investigated in which the patient and donor differed for a single mismatch at HLA-DP in the rejection direction. Patient-derived T lymphocytes circulating at the time of rejection showed direct ex vivo cytotoxic activity against donor-derived B-lymphoblastoid cells as well as other HLA-DPβ1*0901–expressing targets. The presence of HLA-DPβ1*0901–specific effectors in vivo was further confirmed by in vitro stimulation experiments. CD4+ T-cell lines and clones with specific cytotoxic activity against HLA-DPβ1*0901–expressing targets including donor B-lymphoblastoid cells were generated both by nonspecific and by donor-specific in vitro stimulation. Taken together, these data demonstrate that HLA-DP can be the target antigen of cytotoxic CD4+ T lymphocytes involved in peripheral blood stem cell allograft rejection.
Configuration of human dendritic cell cytoskeleton by Rho GTPases, the WAS protein, and differentiation
Authors: Burns Siobhan , Thrasher Adrian J. , Blundell Michael P. , Machesky Laura , Jones Gareth E.
Published: July 2002

The cellular mechanisms that configure the cytoskeleton during migration of dendritic cells (DCs) are poorly understood. Immature DCs assemble specialized adhesion structures known as podosomes at their leading edge; these are associated with the localized recruitment of the Wiskott-Aldrich Syndrome protein (WASp) and the actin organizing actin-related protein 2/3 complex. In immature DCs lacking WASp, podosomes are absent, residual dysmorphic lamellipodia and filopodia are nonpolarized, and migration is severely compromised. Microinjection studies indicate that podosome assembly and polarization require concerted action of Cdc42, Rac, and Rho, thereby providing a link between sequential protrusive and adhesive activity. Formation of podosomes is restricted to cells with an immature phenotype, indicating a specific role for these structures during the early migratory phase.
Purification of human von Willebrand factor–cleaving protease and its identification as a new member of the metalloproteinase family
Authors: Fujikawa Kazuo , Suzuki Hiroshi , McMullen Brad , Chung Dominic
Published: July 2002

von Willebrand factor (vWF) is synthesized in megakaryocytes and endothelial cells as a very large multimer, but circulates in plasma as a group of multimers ranging from 500 to 10 000 kd. An important mechanism for depolymerization of the large multimers is the limited proteolysis by a vWF-cleaving protease present in plasma. The absence or inactivation of the vWF-cleaving protease results in the accumulation of large multimers, which may cause thrombotic thrombocytopenic purpura. The vWF-cleaving protease was first described as a Ca++-dependent proteinase with an apparent molecular weight of approximately 300 kd. Thus far, however, it has not been isolated and characterized. In this study, the purification of human vWF-cleaving protease from a commercial preparation of factor VIII/vWF concentrate by means of several column chromatographic steps, including 2 steps of heparin-Sepharose column, is reported. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis analysis of the anion exchange and gel filtration column fractions showed that the vWF-cleaving protease activity corresponded to a protein band of 150 kd. After reduction, it migrated with an apparent weight of 190 kd. The amino terminal sequence of the 150-kd band was AAGGIL(H)LE(L)L(D)AXG(P)X(V)XQ (single-letter amino acid codes), with the tentative residues shown in parentheses. A search of the human genome sequence identified the vWF-cleaving protease as a new member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin type I motif) family of metalloproteinase. An active site sequence of HEIGHSFGLEHE (single-letter amino acid codes) was located at 150 residues from the N terminus of the protein.
Molecular regulation of CC-chemokine receptor 3 expression in human T helper 2 cells
Authors: Scotet Emmanuel , Schroeder Susanne , Lanzavecchia Antonio
Published: July 2002

In developing T helper 1 (Th1) and Th2 cells the acquisition of effector function is intimately connected with the acquisition of new migratory capacities, as exemplified by differential expression of chemokine receptors. This study investigates the molecular mechanisms responsible for Th2-restricted expression of the CC-chemokine receptor 3 (CCR3). The minimal promoter in T cells was identified in the −149 base pair (bp) upstream sequence that contains a positive regulatory element. A strong negative element was also localized in the flanking intronic sequence. The study further investigates the role of chromatin remodeling in the regulation of this Th2-specific gene. Drugs that affect the chromatin structure facilitate CCR3 expression in T cells. Furthermore, in differentiating Th2 cells, selected regions are associated with acetylated-H3 histones and become more accessible to DNase I. These results suggest that in Th2 cells both cytokine production and migratory capacity are regulated through a similar mechanism involving chromatin remodeling.
Cytokine-inducible CD40 expression in human endothelial cells is mediated by interferon regulatory factor-1
Authors: Wagner Andreas H. , Gebauer Matthias , Pollok-Kopp Beatrix , Hecker Markus
Published: July 2002

Given the significance of CD40–CD40 ligand interactions in chronic inflammatory diseases including atherosclerosis, the transcriptional regulation of CD40 expression as a potential therapeutic target was investigated in human umbilical vein cultured endothelial cells. Exposure to interferon-γ (IFN-γ) plus tumor necrosis factor-α resulted in a marked synergistic de novo expression of CD40, which, according to electrophoretic mobility shift analysis, was attributable to activation of the transcription factors nuclear factor-κB (NF-κB), signal transducer and activator of transcription-1 (STAT-1), and interferon regulatory factor-1 (IRF-1). Subsequent time-course studies revealed that de novo synthesis of IRF-1 preceded that of CD40. Decoy oligodeoxynucleotide (ODN) neutralization of STAT-1 or IRF-1, but not of NF-κB, inhibited cytokine-stimulated CD40 expression by 60% at both the mRNA and protein levels, and this effect was mimicked by antisense ODN blockade of IRF-1 synthesis. In contrast, CD40 expression in response to IFN-γ stimulation was sensitive to neutralization of STAT-1 only. These findings suggest that depending on the cytokine composition, CD40 expression in human endothelial cells under proinflammatory conditions is governed by STAT-1 either directly or indirectly through de novo synthesis of IRF-1. Moreover, decoy ODN neutralization of these transcription factors may provide a novel therapeutic option for interfering with CD40–CD40 ligand-mediated inflammatory responses in vivo.
Tyrosine phosphorylation of B-cell adaptor for phosphoinositide 3-kinase is required for Akt activation in response to CD19 engagement
Authors: Inabe Kazunori , Kurosaki Tomohiro
Published: July 2002

CD19 is a coreceptor that amplifies signaling initiated by antigen cross-linking of the B-cell antigen receptor (BCR). CD19 can also signal independently of BCR coligation. This study shows thatB-cell adaptor forphosphoinositide 3-kinase (BCAP), previously characterized as a substrate of the tyrosine kinases upon BCR engagement, is phosphorylated by cross-linking of CD19. Tyrosine phosphorylation of BCAP, mediated by Lyn, provides binding site(s) for phosphoinositide 3-kinase (PI3K), thereby participating in Akt activation. Thus, these results provide evidence that BCAP serves as an adaptor molecule for CD19 to activate the PI3K pathway in B cells.
Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survival
Authors: Myers Laurie A. , Patel Dhavalkumar D. , Puck Jennifer M. , Buckley Rebecca H.
Published: July 2002

All genetic types of severe combined immunodeficiency (SCID) can be cured by stem cell transplantation from related donors. The survival rate approaches 80%, and most deaths result from opportunistic infections acquired before transplantation. It was hypothesized that the survival rate and kinetics of immune reconstitution would be improved for infants receiving transplants in the neonatal period (first 28 days of life), prior to the development of infections. A 19.2-year retrospective/prospective analysis compared immune function in 21 SCID infants receiving transplants in the neonatal period with that in 70 SCID infants receiving transplants later. Lymphocyte phenotypes, proliferative responses to mitogens, immunoglobulin levels, and T-cell antigen receptor excision circles (TRECs) were measured before transplantation and sequentially after transplantation. Of 21 SCID infants with transplantations in the neonatal period, 20 (95%) survive. Neonates were lymphopenic at birth (1118 ± 128 lymphocytes per cubic millimeter). Infants receiving transplants early developed higher lymphocyte responses to phytohemagglutinin and higher numbers of CD3+ and CD45RA+ T cells in the first 3 years of life than those receiving transplants late (P < .05). TRECs peaked earlier and with higher values (P < .01) in the neonatal transplantations (181 days to 1 year) than in the late transplantations (1 to 3 years). SCID recipients of allogeneic, related hematopoietic stem cells in the neonatal period had higher levels of T-cell reconstitution and thymic output and a higher survival rate than those receiving transplants after 28 days of life. An improved outcome for this otherwise fatal syndrome could be achieved with newborn screening for lymphopenia so that transplantation could be performed under favorable thymopoietic conditions.
Mechanism of factor VIIa–dependent coagulation in hemophilia blood
Authors: Butenas Saulius , Brummel Kathleen E. , Branda Richard F. , Paradis Sara G. , Mann Kenneth G.
Published: July 2002

The ability of factor VIIa to initiate thrombin generation and clot formation in blood from healthy donors, blood from patients with hemophilia A, and in anti–factor IX antibody–induced (“acquired”) hemophilia B blood was investigated. In normal blood, both factor VIIa–tissue factor (TF) complex and factor VIIa alone initiated thrombin generation. The efficiency of factor VIIa was about 0.0001 that of the factor VIIa–TF complex. In congenital hemophilia A blood and “acquired” hemophilia B blood in vitro, addition of 10 to 50 nM factor VIIa (pharmacologic concentrations) corrected the clotting time at all TF concentrations tested (0-100 pM) but had little effect on thrombin generation. Fibrinopeptide release and insoluble clot formation were only marginally influenced by addition of factor VIIa. TF alone had a more pronounced effect on thrombin generation; an increase in TF from 0 to 100 pM increased the maximum thrombin level in “acquired” hemophilia B blood from 120 to 480 nM. Platelet activation was considerably enhanced by addition of factor VIIa to both hemophilia A blood and “acquired” hemophilia B blood. Thus, pharmacologic concentrations of factor VIIa cannot restore normal thrombin generation in hemophilia A and hemophilia B blood in vitro. The efficacy of factor VIIa (10-50 nM) in hemophilia blood is dependent on TF.
Evidence for position effects as a variantETV6-mediated leukemogenic mechanism in myeloid leukemias with a t(4;12)(q11-q12;p13) or t(5;12)(q31;p13)
Authors: Cools Jan , Mentens Nicole , Odero Maria D. , Peeters Pieter , Wlodarska Iwona , Delforge Michel , Hagemeijer Anne , Marynen Peter
Published: July 2002

The ETV6 gene (first identified as TEL) is a frequent target of chromosomal translocations in both myeloid and lymphoid leukemias. At present, more than 40 distinct translocations have been cytogenetically described, of which 13 have now also been characterized at the molecular level. These studies revealed the generation of in-frame fusion genes between different domains of ETV6 and partner genes encoding either kinases or transcription factors. However, in a number of cases—including a t(6;12)(q23;p13), the recurrent t(5;12)(q31;p13), and some cases of the t(4;12)(q11-q12;p13) described in this work—functionally significant fusions could not be identified, raising the question as to what leukemogenic mechanism is implicated in these cases. To investigate this, we have evaluated the genomic regions at 4q11-q12 and 5q31, telomeric to the breakpoints of the t(4;12)(q11-q12;p13) and t(5;12)(q31;p13). The homeobox geneGSH2 at 4q11-q12 and the IL-3/CSF2locus at 5q31 were found to be located close to the respective breakpoints. In addition, GSH2 and IL-3 were found to be ectopically expressed in the leukemic cells, suggesting that expression of GSH2 and IL-3 was deregulated by the translocation. Our results indicate that, besides the generation of fusion transcripts, deregulation of the expression of oncogenes could be a variant leukemogenic mechanism for translocations involving the 5′ end of ETV6, especially for those translocations lacking functionally significant fusion transcripts.
Self‐potentials associated with the Yanacocha high‐sulfidation gold deposit in Peru
Authors: Goldie Mark
Published: July 2002

Significant self‐potential (SP) anomalies characterize the large silica bodies associated with high‐sulfidation oxide gold deposits in the Yanacocha district, Peru. Large SP effects and high apparent resistivities have been observed that coincide with areas of intense silicification. Negative SP anomalies of several volts have been routinely recorded on numerous projects and deposits. The peak value measured was −10.2 V. A direct relationship is shown to exist between the magnitude of an SP response and the size and apparent resistivity of a silica body. Extensive field measurements over numerous high‐sulfidation deposits show that the negative SP effect increases with the size and/or resistivity contrast associated with these unique mineral deposits.
Low‐cost geophysical investigations of a paleochannel aquifer in the Eastern Goldfields, Western Australia
Authors: Holzschuh Josef
Published: July 2002

Compressional (P) wave and shear (S) wave seismic reflection techniques were used to delineate the sand and gravel aquifer within a highly saline clay‐filled paleochannel in the Eastern Goldfields of Western Australia. The seismic refraction and gravity methods were also used to investigate the paleochannel. The unsaturated loose fine‐grained sand up to 10 m in depth at the surface is a major factor in degrading subsurface imaging. The seismic processing needed to be precise, with accurate static corrections and normal moveout corrections. Deconvolution enhanced the aquifer and other paleochannel reflectors. P‐wave reflection and refraction layer depths had good correlation and showed a total of six boundaries: (1) water table, (2) change in velocity (compaction) in the paleochannel sediments, (3) sand and gravel aquifer, (4) red‐brown saprolite and green saprolite boundary, (5) weathered bedrock, and (6) unweathered bedrock. P‐wave explosive and hammer sources were found to have similar signal characteristics, and the aquifer and bedrock were both imaged using the hammer source. The deep shots below the water table have the most broadband frequency response for reflections, but stacking clear reflections was difficult. The S‐wave reflection results showed high lateral and vertical resolution of the basal saprolite clay, the sand and gravel aquifer, and very shallow clays above the aquifer. The S‐wave reflection stacking velocities were 10–20% of the P‐waves, increasing the resolution of the S‐wave section. The gravity data were modelled to fit the known drilling and P‐wave seismic reflection depths. The refraction results did not identify the top of bedrock, so refraction depths were not used for the gravity modeling in this highly weathered environment. The final gravity model mapped the bedrock topography beyond the lateral extent of the seismic and drilling data.
Dielectric permittivity and resistivity mapping using high‐frequency, helicopter‐borne EM data
Authors: Huang Haoping , Fraser Douglas C.
Published: July 2002

The interpretation of helicopter‐borne electromagnetic (EM) data is commonly based on the transformation of the data to the apparent resistivity under the assumption that the dielectric permittivity is that of free space and so displacement currents may be ignored. While this is an acceptable approach for many applications, it may not yield a reliable value for the apparent resistivity in resistive areas at the high frequencies now available commercially for some helicopter EM systems.

We analyze the feasibility of mapping spatial variations in the dielectric permittivity and resistivity using a high‐frequency helicopter‐borne EM system. The effect of the dielectric permittivity on the EM data is to decrease the in‐phase component and increase the quadrature component. This results in an unwarranted increase in the apparent resistivity (when permittivity is neglected) for the pseudolayer half‐space model, or a decrease in the apparent resistivity for the homogeneous half‐space model. To avoid this problem, we use the in‐phase and quadrature responses at the highest frequency to estimate the apparent dielectric permittivity because this maximizes the response of displacement currents. Having an estimate of the apparent dielectric permittivity then allows the apparent resistivity to be computed for all frequencies. A field example shows that the permittivity can be well resolved in a resistive environment when using high‐frequency helicopter EM data.
Uncertainty in determining interval velocities from surface reflection seismic data
Authors: Kosloff Dan D. , Sudman Yonadav
Published: July 2002

The ability of reflection seismic data to uniquely determine the subsurface velocity has been uncertain. This paper uses a tomographic approach to study the resolution of typical seismic survey configurations. The analysis is first carried out in the spatial Fourier domain for the case of a single horizontal reflector. It is found that for a ratio of maximum offset to layer depth of one, the lateral resolution is very low for velocity and interface depth variations of wavelengths of approximately two‐and‐a‐half times the layer thickness. The resolution improves with an increase in the ratio of maximum offset to layer depth. The results of the analysis in the Fourier domain are confirmed by results from a least‐squares tomographic algorithm. It is found that regularization of the tomography by adding damping terms suppresses the spurious oscillations resulting from the areas of low resolution at the expense of loss of resolution at the shorter spatial wavelengths. Analysis of the single layer response for 3‐D survey geometry shows that a 3‐D acquisition with multiazimuthal coverage has the potential to significantly improve velocity determination.
A Randomized Clinical Trial of Oral versus Intramuscular Delivery of Steroids in Acute Exudative Pharyngitis
Authors: Marvez‐Valls Eduardo G. , Stuckey Ashley , Ernst Amy A.
Published: July 2002

Previous study has shown that the use of intramuscular (IM) steroid leads to improved symptoms in patients with group A beta‐hemolytic streptococcus (GABHS). Objective: To compare oral with IM steroids as an adjunct to antibiotic therapy in the treatment of acute exudative pharyngitis. The null hypothesis was that there would be no difference in effectiveness of oral versus IM steroids. Methods: The study was a randomized, double‐blind outpatient clinical trial. After consent was obtained, each patient was asked to rate his or her pain on a 10‐cm numbered visual analog scale (VAS; 0‐10). All of the patients received injectable benzathine penicillin or, if allergic to penicillin, a ten‐day course of polyenteric‐coated erythromycin. Each patient was randomized to receive either injectable steroid plus oral placebo or injectable placebo plus oral steroid. All medications were given in the emergency department. All patients were contacted by telephone at 24 hours (first follow‐up) and 48 hours (second follow‐up) by one of the study investigators and asked to rate their pain based on another VAS. If their pain was not resolved by 48 hours, they were called again daily for the third to seventh day after the initial visit. The time to total resolution of the sore throat was documented. The main outcome measures were time to complete relief of pain and VAS scores. Pain medication was not controlled; however, use of pain medications and amounts were recorded. Results: A total of 78 patients were initially enrolled in the study. Eight patients were excluded from the statistical analysis because of inability to follow up. A total of 70 were entered, with 35 randomized to IM steroid plus oral placebo and 35 to IM placebo plus oral steroid. There was no difference in pain scores for the oral versus IM group at first follow‐up (p = 0.13) and second follow‐up (p = 0.82), and in number of hours to relief of pain (p = 0.06). Using repeated‐measures analysis of variance, no difference in the effects of the two medications over time was detected (p = 0.83). Conclusions: The results of this clinical trial suggest that oral steroid and IM steroid provide similar levels of pain relief in acute exudative pharyngitis.
Activity of Oxaliplatin in Patients With Relapsed or Cisplatin-Refractory Germ Cell Cancer: A Study of the German Testicular Cancer Study Group
Authors: Kollmannsberger C. , Rick O. , Derigs H.-G. , Schleucher N. , Schöffski P. , Beyer J. , Schoch R. , Sayer H.G. , Gerl A. , Kuczyk M. , Spott C. , Kanz L. , Bokemeyer C.
Published: July 2002

PURPOSE: To investigate the efficacy and toxicity of oxaliplatin, a diaminocyclohaxane platinum derivative with incomplete cross-resistance to cisplatin in patients with relapsed or cisplatin-refractory germ cell cancer.

PATIENTS AND METHODS: Thirty-two patients with nonseminomatous cisplatin-refractory germ cell cancer or relapsed disease after high-dose chemotherapy (HDCT) plus autologous stem-cell support were treated with single-agent oxaliplatin 60 mg/m2 on days 1, 8, and 15 repeated every 4 weeks (group 1; n = 16) or oxaliplatin 130 mg/m2 given on days 1 and 15 of a 4-week cycle (group 2; n = 16). Patients were pretreated with a median of seven (range, three to 13) cisplatin-containing treatment cycles; 78% had received carboplatin/etoposide-based HDCT before oxaliplatin therapy. Twenty-seven patients (84%) were considered refractory (n = 20; 63%) or absolutely refractory (n = 7; 22%) to cisplatin therapy.

RESULTS: Overall, four patients achieved a partial remission (13%; 95% confidence interval, 1% to 24%). Two additional patients achieved disease stabilization. All responses were observed in cisplatin-refractory patients, including three who had not responded to previous HDCT. Patients received a median two cycles of oxaliplatin with a median cumulative dose of 350 mg/m2. Hematologic toxicity was generally mild, with five patients developing grade 3/4 thrombocytopenia. Nonhematologic side effects consisted mainly of nausea/vomiting. One patient developed grade 3 neurotoxicity.

CONCLUSION: Considering the particularly unfavorable prognostic characteristics of this patient population compared with patients from previous trials for new drugs in germ cell cancer, eg, paclitaxel and gemcitabine, a 13% overall response rate and a 19% response rate in the group treated with oxaliplatin 130 mg/m2 seems to be of interest. Oxaliplatin may be a palliative treatment option for this patient population, and evaluation in combination regimens is warranted.
Am I a Survivor?
Authors: Texler Cara E.
Published: December 2024

In this narrative medicine essay, a pediatric hospitalist who had undergone a double mastectomy after atypical ductal hyperplasia was detected in one of her breasts wonders whether the pain and loss from that surgery renders her a cancer survivor.
Second Primary Cancer After Chimeric Antigen Receptor–T-Cell Therapy
Authors: Patel Shyam A. , Spiegel Jay Y. , Dahiya Saurabh
Published: December 2024

Importance

The commercialization of chimeric antigen receptor–T-cell (CAR-T) therapy has changed the landscape of treatment of hematological cancers. Numerous studies from the early 2000s paved the way for cell-based targeted therapeutics, which have been established as practice-changing therapies in lymphoma, leukemia, and multiple myeloma. However, there has been some recent concern about the risk for second primary cancers (SPCs).

Observations

Multiple cases of SPCs arising after CAR-T therapy have been reported to the US Food and Drug Administration. Most SPCs have been negative for the chimeric antigen receptor transgene, with rare reports of transgene-positive cancers. This review summarizes the most salient literature on epidemiology and pathobiology of SPCs after CAR-T therapy. Additionally, a discussion is provided on potential mitigation strategies for SPCs after CAR-T therapies.

Conclusions and Relevance

The results of this review suggest that there are limited data to suggest that inadvertent transgene insertion is associated with SPCs in the post–CAR-T setting. Nonetheless, evidence-based practical solutions and scientific strategies for risk mitigation can be implemented. These include optimization of T-cell manufacturing, application of safer synthetic immunobiology, and implementation of high-fidelity genomic testing, including baseline screening for clonal hematopoiesis. These strategies may inform optimal design of the next generation of CAR-T products that confer minimal risk for SPCs such that the risk-benefit profile remains favorable to proceed with CAR-T administration for eligible patients.
Oncological Safety of MRI-Informed Biopsy Decision-Making in Men With Suspected Prostate Cancer
Authors: Hamm Charlie A. , Asbach Patrick , Pöhlmann Anna , Schoots Ivo G. , Kasivisvanathan Veeru , Henkel Thomas O. , Johannsen Manfred , Speck Thomas , Baur Alexander D. J. , Haas Matthias , Collettini Federico , Penzkofer Tobias , Savic Lynn J. , Konietschke Frank , Weißbach Lothar , Hamm Bernd , König Frank , Cash Hannes
Published: December 2024

Importance

The magnetic resonance imaging (MRI) pathway for diagnosing clinically significant prostate cancer (csPCa; defined as International Society of Urological Pathology grade group ≥2) uses multiparametric MRI (mpMRI) for prostate biopsy (PB) decision-making. However, the intermediate impact on patient outcomes in men with negative MRI results avoiding PB and men with positive MRI results without PCa remains unknown.

Objective

To assess the feasibility and safety of a community-based MRI diagnostic strategy in men with suspected PCa using 3-year active monitoring.

Design, Setting, and Participants

This multisite, longitudinal cohort trial took place across 54 community-based urology practices and 2 radiology imaging centers at a referral academic institution in Berlin, Germany. Eligible participants aged 18 to 75 years with clinically suspected PCa were enrolled between September 2016 and December 2017 and monitored for 3 years. Final analysis was reported on December 23, 2023.

Exposures

Participants underwent 3-T mpMRI. Men with findings suspected to be PCa were recommended for targeted PB (diagnostic phase). Men with negative mpMRI results or positive mpMRI results with benign findings at PB were systematically monitored for 3 years (monitoring phase). Clinical visits were recommended every 6 months.

Main Outcomes and Measures

The total proportion of men avoiding PB and those with csPCa.

Results

A total of 593 men (median [IQR] age, 64 [58-70] years) underwent mpMRI, with 286 (48%) having negative MRI results, 261 (44%) avoiding PB initially, and 242 (41%) avoiding PB over 3 years. csPCa was detected in 161 (27%) men after immediate PB, increasing to 172 (29%) men after 3 years. Seven men with negative MRI results were diagnosed with PCa by immediate PB (including 4 cases of csPCa), while 279 entered monitoring. Three-year monitoring was completed by 233 (84%) men, with 7 diagnoses of csPCa. Of 307 men with positive MRI results, 58 (19%) showed no PCa after immediate PB, of which 41 (71%) completed monitoring and 4 (7%) were diagnosed with csPCa.

Conclusions and Relevance

In this cohort study, men with negative mpMRI results avoiding biopsy were not at elevated risk of csPCa. The study confirms the oncological safety of the prebiopsy MRI strategy of avoiding an immediate PB after negative MRI results when a programmatic safety net is in place.
A Magnetically Self‐Aligning, Fast Full‐Device Self‐Healing, Skin‐Attachable Liquid Metal Strain Sensor Based on Photothermal Polyurethane
Authors: Kim Jung Wook , Kim Somin , Lee Jinyoung , Kim Yongju , Ha Jeong Sook
Published: December 2024

There is a growing need for research on self‐healing materials capable of spontaneously repairing physical damage, allowing the fabrication of highly durable wearable devices featuring flexibility and stretchability. Herein, the study reports on the fabrication of a novel, magnetically aligning, fully and rapidly self‐healing skin‐attachable biosensor based on newly synthesized photothermally self‐healing polyurethane. By introducing photothermal amine‐capped aniline trimers to selectively self‐healable polyurethane, the synthesized self‐healing polymer achieves a fast and high recovery rate of 81.1% from complete bisection upon laser irradiation for just 3 min. Additionally, a thin‐film type strain sensor fabricated via the spray patterning of liquid metal EGaIn as an electrode onto the surface of the self‐healing polymer exhibits a high sensitivity to strain from deformation, enabling the real‐time monitoring of bio‐signals. Furthermore, the integration of a magnetic aligning layer directly patterned and embedded onto the self‐healing polymer enhances the self‐healing performance of the sensor after damage by 4.3 times on average, compared to when using manual alignment. In short, this work demonstrates a high‐performance fully self‐healing electronic device via the synthesis of novel fast self‐healing photothermal polymers and the introduction of patterned liquid metal electrodes and magnetic alignment layers.
Synergistic Treatments of Bulk and Surface in Tin‐Lead Mixed Perovskite for Efficient All‐Perovskite Tandem Solar Cells
Authors: Xie Jiankai , Jin Xiaonan , Cao Jiupeng , Shu Yuting , Yan Wenjian , Han Lingui , Duan Jibiao , Wang Fangfang , Dong Jingjin , Wang Aifei , Huang Wei , Qin Tianshi
Published: December 2024

Narrow‐bandgap (NBG) perovskites have attracted significant attention for their promising potential as light‐absorbing materials in tandem solar cells. However, tin‐lead mixed perovskites face a major limitation of the facile oxidation of Sn2⁺, leading to Sn vacancies in the perovskite films. In this study, sodium triacetoxyborohydride (STAB) is introduced as an antioxidant, while potassium (5‐bromo‐2‐fluoropyridin‐3‐yl)trifluoroborate (PBFT) is employed as a surface modifier for mixed tin‐lead perovskites. This combined approach not only suppresses Sn2⁺ oxidation but also promotes the formation of high‐quality perovskite films. Furthermore, the induced energy band bending at the perovskite/C60 interface substantially enhances charge transfer. Consequently, the optimized device achieves a power conversion efficiency (PCE) of 23.41% with excellent illumination stability. When paired with a wide‐bandgap (WBG) semi‐transparent perovskite solar cell (PSC), the resulting four‐terminal (4‐T) all‐perovskite tandem solar cell attains a remarkable efficiency of 27.37%.
Bacterial Microenvironment‐Responsive Microneedle Patches for Real‐Time Monitoring and Synergistic Eradication of Infection
Authors: Xu Yigang , Zhang Di , Kang Xiaoying , Zhang Pengcheng , Chen Ting , Li Yi , Wu Huifan , Qi Ji , Li Xueping , Bing Wei , Li Wen
Published: December 2024

Bacterial infection stands as one of the biggest threats to public health. In recent years, the rise of diverse drug‐resistant bacteria has significantly compromised the efficacy of existing antibiotics in eradicating them, and the formation of biofilms has further weakened the treatment effect. In this study, a pH‐responsive photodynamic probe, TI, is developed and assembled with a ROS‐reactive carbon monoxide (CO) donor, and then encapsulated within a HA‐based microneedle patch, ultimately creating the theranostic microneedle platform. The microneedle structure enhances the mechanical penetration of both the molecular probe and CO donor into the biofilm at the site of wound infection. When encountering the acidic microenvironment of the wound, TI undergoes dynamic molecular structural changes, resulting in a notable near‐infrared fluorescent output for detecting infections and assessing their severity. Concurrently, the nanoprobes unleash their ROS‐generating potential, which can not only directly eliminate bacteria through oxidative damage, but also trigger the release of CO for adjunct gas therapy. Overall, the integrated diagnostic and therapeutic microneedle platform provides a promising approach to addressing wound infections, and alleviating the challenges posed by antibiotic resistance, offering significant hope in the realm of infection care management.
Positive Magneto‐Electric Couplings in Epitaxial Multiferroic SrMnO3 Thin Film
Authors: Mandal Arup Kumar , Chowdhury Sourav , Parate Shubham Kumar , Surampalli Akash , Rawat Ritu , Biswas Kartick , Mondal Suryakanta , Nukala Pavan , Phase D. M. , Choudhary R. J.
Published: December 2024

This study demonstrates the magneto‐dielectric (MD) properties of high quality epitaxially strain multiferroic SrMnO3 thin film on conducting Nb doped SrTiO3 substrate. The study observes considerable high positive MD coupling near room temperature and across the anti‐ferromagnetic transition temperature of SrMnO3. The dielectric maxima of the grown film is above room temperature, which confirms the room temperature ferroelectric nature of the grown film. From out‐of‐plan polarization and PUND (Positive Up Negative Down) measurements in the presence of magnetic field, it is confirmed that the polarization value of grown SrMnO3 thin film increases with an increase in magnetic field. In this study, the oxygen off‐stoichiometry concentration is also varied by varying oxygen partial pressure during deposition and is able to create Mn4+, Mn3+, and Mn2+ in the grown films. Despite having mixed Mn states, SrMnO3 thin films remain in the insulating phase. So, the insulating nature of SrMnO3 thin film is robust with respect to oxygen off‐stoichiometry and vacancy/substrate induced strain mediated change in the crystal field. The study has also demonstrated the variation of MD in SrMnO3 thin film by change in oxygen vacancy induced modification in crystal field.
Bioinspired Ionic Elastomer with Skin‐Like Piezo‐Ionic Dynamics Enabled by a Self‐Confined Multi‐Interaction Network
Authors: Fang Zhiyue , Wang Lei , Liang Cuiyuan , Qiu Jinhua , Zhang Tongye , Xu Donghua , Qi Dianpeng , Luan Shifang , Shi Hengchong
Published: December 2024

Soft ionic elastomers have attracted considerable research interest in mimicking the multiple functions of human skin. However, these ionic elastomers struggle to simultaneously achieve controllable ion dynamics and other essential performance, such as self‐healing ability and appropriate mechanical robustness. Herein, bioinspired by Piezo proteins and integrins in human skin, thioctic acid (TA)‐derived ionic elastomers with skin‐like piezo‐ionic dynamics are fabricated via a multi‐confined interaction network. This bionic network is constructed by introducing a diene comonomer and lithium salt filler into polysulfides (poly (TA)), generating many dynamic interactions (various hydrogen bonds and lithium bonds). These dynamic interactions can bind ions to the polysulfides and be destroyed under external pressure stimulation, achieving controllable ion pumping behavior. This unique design concept enables these ionic elastomers to selectively respond to pressure (the optimal sample exhibits 152 times signal intensity with a sensitivity of 49.53‐1.13 kPa−1), along with leak prevention, recyclability, and degradability. Besides, these interactions also serve as sacrificial bonds and self‐healing sites to synergistically enhance all aspects of performance, yielding a high modulus of 2.47 MPa and outstanding self‐healing efficiency of 98%. It is believed that this work could create a new approach for utilizing sustainable materials in next‐generation “green” flexible sensors.
Recent Progress for Designing of Catalysts for Photothermal Conversion of Plastic Wastes
Authors: He Dongpo , Huang Guangbing , Zhou Ziyao , Hu Qinyuan , Ding Jinyu , Wu Jiacong , Li Mengqian , Ruan Xiaowen , Jiao Xingchen , Xie Yi
Published: December 2024

In the context of the global struggle against plastics, catalytic upgrading and recycling of plastics has been the subject of considerable attention as a powerful strategy for achieving both environmental remediation and value‐added chemical production. Compared with conventional recycling methods, the emerging photothermal catalysis methodology integrates photochemical and thermal catalytic processes, which outstands with features of high conversion efficiency and mild reaction conditions. Herein, a comprehensive review for the recent research progress of photothermal conversion of plastic waste is presented. First, the types of photothermal catalysts for plastic upcycling are classified into three categories, metallic materials, semiconductor materials, and carbon‐based materials, based on the photothermal conversion mechanism. Their potential mechanisms as powerful photothermal converters and future directions in photothermal conversion of plastics are highlighted. Furthermore, the logical structural design of photothermal catalytic materials are summarized to enhance photothermal performance in plastic conversion. Finally, future opportunities and challenges in this promising but nascent field are discussed, and future research directions for photothermal conversion of plastics are presented.
A Pomegranate‐Like Nanolayer Featuring A Core‐Shell Architectural Design for Thermal‐Mechanical‐Electromagnetic Responses and Sensor
Authors: Fan Xiao‐Xuan , Zhang Min , Zhang Xin‐Ci , Li Lin , Cao Mao‐Sheng
Published: December 2024

Multifunctional electromagnetic wave (EMW) absorbing materials are attracting attention because of their potential applications in medical, livelihood, and military. In this study, a pomegranate‐like nanolayer featuring a core‐shell architecture (PNCS) is prepared using a confinement strategy. Introducing metal atoms into this unique pomegranate‐like design (M‐PNCS, M = Mn, Fe, Co, Ni, and Cu) effectively tuned the electromagnetic response and improved the electromagnetic functions. The Mn‐PNCS composite exhibited the highest electromagnetic absorption. Its reflection loss (RL) reached −62.39 dB with an effective absorption bandwidth (EAB) at 1.8 mm of 6.0 GHz. As the charge transport capacity of the Mn‐PNCS increases, its absorption can be transformed into shielding, with a green shielding index of up to 3.54. On this basis, Mn‐PNCS is used to fabricate a multifunctional film and a new design of strain sensor. This multifunctional film integrated electromagnetic absorption, thermal insulation, hydrophobicity, flexibility, and sensing, thus showing potential for use in wearable electromagnetic protective clothing. In addition, the sensors in the simulation design achieved strain sensing through the coupling effect between the Mn‐PNCS patterns. These findings demonstrate that Mn‐PNCS is an excellent multifunctional material with potential applications in the technical fields of EMW absorption, electromagnetic shielding, and wearable devices.
Mechanism of Hot‐Carrier Photoluminescence in Sn‐Based Perovskites
Authors: Tekelenburg Eelco K. , Camargo Franco V. A. , Filippetti Alessio , Mattoni Alessandro , van de Ven Larissa J. M. , Pitaro Matteo , Cerullo Giulio , Loi Maria A.
Published: December 2024

Metal halide perovskites have shown exceptionally slow hot‐carrier cooling, which has been attributed to various physical mechanisms without reaching a consensus. Here, experiment and theory are combined to unveil the carrier cooling process in formamidinium (FA) and caesium (Cs) tin triiodide thin films. Through impulsive vibrational spectroscopy and molecular dynamics, much shorter phonon dephasing times of the hybrid perovskite, which accounts for the larger blueshift in the photoluminescence seen at high excitation density for FASnI3 compared to CsSnI3 is reported. Density functional theory investigations reveal that the largest contribution to the blueshift is accounted by a giant, dynamic band‐filling effect in Sn‐based perovskites, which in turn can explain the cooling disparity with the Pb‐based counterparts. Several years after the first experimental observations, here a deeper understanding of the cooling mechanism of these materials is provided. Design principles for hot‐carrier materials, which may be useful for future implementations of hot‐carrier solar cells are further provided.
Spatiotemporal Nano‐Regulator Unleashes Anti‐Tumor Immunity by Overcoming Dendritic Cell Tolerance and T Cell Exhaustion in Tumor‐Draining Lymph Nodes
Authors: Wang Ruonan , Li Huixin , He Shasha , Feng Yuanji , Liu Cong , Hao Kai , Zhou Danhua , Chen Xiaoyuan , Tian Huayu
Published: December 2024

Lymph nodes are crucial immune foci as the primary target for cancer immunotherapy. However, the anti‐tumor functions of tumor‐draining lymph nodes (TDLNs) are critically suppressed by tumors. Here, a novel spatiotemporal nano‐regulator is presented, designed to modulate the dendritic cells (DCs) in TDLNs, establishing a supportive niche for immune surveillance. The DC‐mediated nano‐regulator (DNR) is established by the self‐assembly of an imidazoquinoline (IMDQ) prodrug, inhibitory immune checkpoint (ICP) siRNA, and mannan (a TLR4 agonist). This unique design leverages the spatiotemporal activation of TLR4 and TLR7/8, thereby optimizing DC maturation and cytokine production. This further promotes efficient T cell priming. Simultaneously, the ICP‐targeting siRNA mitigates the tolerogenic effects induced by tumor‐derived factors and TLR activation, preventing T cell exhaustion. In essence, DNR facilitates potent remodeling of TDLNs and the tumor microenvironment, activating the anti‐tumor immunity cascade. When combined with vaccines, DNR greatly promotes tumor regression and the establishment of long‐term immunological memory.
The Role of Silicon Technology in Organ‐On‐Chip: Current Status and Future Perspective
Authors: Skottvoll Frøydis Sved , Escobedo‐Cousin Enrique , Mielnik Michal Marek
Published: December 2024

Organ‐on‐chip (OoC) systems are microfluidic in vitro platforms constructed to expand the current understanding of organ‐level physiology and response. This technology holds significant potential to transform drug discovery, precision medicine, and disease modeling while reducing animal model use. Recent developments in OoC technology have shown great promise, demonstrated using relatively simple microfluidic designs. Currently, the consensus in the OoC‐related literature is that the future of OoC technology lies in the development of robust platforms that offer higher throughput, improved customization, and higher levels of integration of sensing and actuation modalities. The implementation of silicon micro‐nanofabrication technologies can foster such a transition, but the application in the field remains limited. In this review, an overview of silicon micro‐nanofabrication technologies is provided that have been or can be applied in the realization of compact OoC systems, with focus on integrated actuation and sensing modalities. Emerging technologies are highlighted for the heterogeneous integration of silicon‐based and polymer‐based components in OoC systems for the realization of compact and multimodal OoC platforms. Finally, the most promising avenues are outlined for silicon technology within the framework of OoC and the future of biomedical research and personalized medicine.
Non‐Invasive Ammonia Detection on Cancer Cell Surfaces Using Liquid Crystal Elastomer
Authors: Khan Mashooq , Li Weiwei , Hu Qiongzheng , Lin Jin‐Ming , Lin Ling
Published: December 2024

Delving into the intricate world of cancer cells requires a profound understanding of the signaling molecules released from the cells. In this contribution, ammonia (NH3) is monitored, a small signaling molecule and potential cancer biomarker, on the cell surfaces through liquid crystal elastomer microspheres (LCEM) at the single‐cell level. The LCEM are synthesized from molecular building blocks, 7‐octenoic acid (7OAc) and 2‐methyl‐1,4‐phenylene bis(4‐((acryloyloxy)hexyl)oxy) benzoate (RM82) and adorned on the surfaces of healthy human umbilical vein endothelial cells (HUVEC), and cancerous, human primary glioblastoma (U87), human colon carcinoma (CaCo‐2), and human breast adenocarcinoma (MCF7) cells, cultured within microfluidic channels. The ethereal release of NH3 from living cells is monitored through a radial‐to‐concentric transfiguration of LCEM. The cellular heterogeneity among cancerous cell populations is unraveled by mapping the LCEM morphology on 100 cells of each cell line. The LCEM paves the way for designing probes that offer selective, simplistic, and label‐free monitoring of the biochemical processes unfurling on the surfaces of living cells, which are challenging to measure through other analytical techniques.