bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytosolic Aminopeptidases Influence MHC Class I-Mediated Antigen Presentation in an Allele-Dependent Manner
Authors: Kim Eunkyung , Kwak Heechun , Ahn Kwangseog
Published: November 2009

Antigenic peptides presented by MHC class I molecules are generated mainly by the proteasome in the cytosol. Several cytosolic aminopeptidases further trim proteasomal products to form mature epitopes or individual amino acids. However, the distinct function of cytosolic aminopeptidases in MHC class I Ag processing remains to be elucidated. In this study, we show that cytosolic aminopeptidases differentially affect the cell surface expression of MHC class I molecules in an allele-dependent manner in human cells. In HeLa cells, knockdown of puromycin-sensitive aminopeptidase (PSA) by RNA interference inhibited optimal peptide loading of MHC class I molecules, and their cell surface expression was correspondingly reduced. In contrast, depletion of bleomycin hydrolase (BH) enhanced optimal peptide loading and cell surface expression of MHC class I molecules. We did not find evidence on the effect of leucine aminopeptidase knockdown on the MHC class I Ag presentation. Moreover, we demonstrated that PSA and BH influence the peptide loading and surface expression of MHC class I in an allele-specific manner. In the absence of either PSA or BH, the surface expression and peptide-dependent stability of HLA-A68 were reduced, whereas those of HLA-B15 were enhanced. The surface expression and peptide-dependent stability of HLA-A3 were enhanced by BH knockdown, although those of HLA-B8 were increased in PSA-depleted conditions.
TLR Cross-Talk Specifically Regulates Cytokine Production by B Cells from Chronic Inflammatory Disease Patients
Authors: Jagannathan Madhumita , Hasturk Hatice , Liang YanMei , Shin Hyunjin , Hetzel Jeremy T. , Kantarci Alpdogan , Rubin Daniel , McDonnell Marie E. , Van Dyke Thomas E. , Ganley-Leal Lisa M. , Nikolajczyk Barbara S.
Published: November 2009

Chronic systemic inflammation links periodontal disease and diabetes to increased incidence of serious comorbidities. Activation of TLRs, particularly TLR2 and TLR4, promotes chronic systemic inflammation. Human B cells have been generally thought to lack these TLRs. However, recent work showed that an increased percentage of circulating B cells from inflammatory disease patients express TLR2 and TLR4, and that TLR engagement on B cells resulted in unexpected changes in gene expression. New data show that B cells from inflammatory disease patients secrete multiple cytokines in response to different classes of TLR ligands. Furthermore, the B cell response to combinations of TLR ligands is cytokine- and ligand-specific. Some cytokines (IL-1β and IL-10) are predominantly regulated by TLR4, but others (IL-8 and TNF-α) are predominantly regulated by TLR2, due in part to TLR-dictated changes in transcription factor/promoter association. TLR2 and TLR9 also regulate B cell TLR4 expression, demonstrating that TLR cross-talk controls B cell responses at multiple levels. Parallel examination of B cells from periodontal disease and diabetes patients suggested that outcomes of TLR cross-talk are influenced by disease pathology. We conclude that disease-associated alteration of B cell TLR responses specifically regulates cytokine production and may influence chronic inflammation.
Selective Down-Regulation of Neutrophil Mac-1 in Endotoxemic Hepatic Microcirculation via IL-10
Authors: Menezes Gustavo Batista , Lee Woo-Yong , Zhou Hong , Waterhouse Christopher Curtis Matchett , Cara Denise Carmona , Kubes Paul
Published: November 2009

Hepatic neutrophil adhesion during endotoxemia is an integrin-independent, CD44-dependent process. Because integrins function in other endotoxemic vasculatures, we used spinning disk confocal intravital microscopy to assess whether LPS down-modulated integrin functions in sinusoids. First, we applied fMLP onto the liver surface, and compared it with systemic LPS administration. Local fMLP caused neutrophil adhesion, crawling, and emigration for at least 2 h. Surprisingly, the number of adherent and crawling neutrophils was markedly reduced in Mac-1−/− and ICAM-1−/− mice, but not in mice treated with anti-CD44 mAb. By contrast, systemic LPS injection induced a robust accumulation of neutrophils in sinusoids, which was dependent on CD44, but not on integrins. Strikingly, local fMLP could not induce any integrin-dependent adhesion in endotoxemic mice treated with anti-CD44 mAb, indicating that Mac-1-dependent neutrophil adhesion was inhibited by LPS. This response was localized to the hepatic microvasculature because neutrophils still adhered via integrins in brain microvasculature. ICAM-1/ICAM-2 levels were not decreased, but following LPS treatment, Mac-1 was down-regulated in neutrophils localized to liver, but not in the circulation. Mac-1 down-regulation in neutrophils was not observed in IL-10−/− mice. In vitro neutrophil incubation with IL-10 induced direct decrease of Mac-1 expression and adhesivity in LPS-stimulated neutrophils. Therefore, our data suggest that Mac-1 is necessary for neutrophil adhesion and crawling during local inflammatory stimuli in sinusoids, but during systemic inflammation, neutrophils are exposed to high concentrations of IL-10, leading to a CD44-dependent, integrin-independent adhesion. This may be a mechanism to keep neutrophils in sinusoids for intravascular trapping.
Systematic Classification of Primary Immunodeficiencies Based on Clinical, Pathological, and Laboratory Parameters
Authors: Samarghitean Crina , Ortutay Csaba , Vihinen Mauno
Published: November 2009

The classification of diseases has several important applications ranging from diagnosis and choice of treatment to demographics. To date, classifications have been successfully created manually, often within international consortia. Some groups of diseases, such as primary immunodeficiencies (PIDs), are especially hard to nosologically cluster due, on one hand, to the presence of a wide variety of disorders and, in contrast, because of overlapping characteristics. More than 200 PIDs affecting components of the innate and adaptive immune systems have been described. Clinical, pathological, and laboratory characteristics were collected and used to group PIDs. A consensus of at least five independent methods provided a novel classification of 11 groups, which revealed previously unknown features and relationships of PIDs. Comparison of the classification to independent features, including the severity and therapy of the diseases, functional classification of proteins, and network vulnerability, indicated a strong statistical support. The method can be applied to any group of diseases.
CD39+Foxp3+ Regulatory T Cells Suppress Pathogenic Th17 Cells and Are Impaired in Multiple Sclerosis
Authors: Fletcher Jean M. , Lonergan Roisin , Costelloe Lisa , Kinsella Katie , Moran Barry , O'Farrelly Cliona , Tubridy Niall , Mills Kingston H. G.
Published: November 2009

Despite the fact that CD4+CD25+Foxp3+ regulatory T cells (Treg cells) play a central role in maintaining self-tolerance and that IL-17-producing CD4+ T cells (Th17 cells) are pathogenic in many autoimmune diseases, evidence to date has indicated that Th17 cells are resistant to suppression by human Foxp3+ Treg cells. It was recently demonstrated that CD39, an ectonucleotidase which hydrolyzes ATP, is expressed on a subset of human natural Treg cells. We found that although both CD4+CD25highCD39+ and CD4+CD25highCD39− T cells suppressed proliferation and IFN-γ production by responder T cells, only the CD4+CD25highCD39+, which were predominantly FoxP3+, suppressed IL-17 production, whereas CD4+CD25highCD39− T cells produced IL-17. An examination of T cells from multiple sclerosis patients revealed a normal frequency of CD4+CD25+CD127lowFoxP3+, but interestingly a deficit in the relative frequency and the suppressive function of CD4+CD25+CD127lowFoxP3+CD39+ Treg cells. The mechanism of suppression by CD39+ Treg cells appears to require cell contact and can be duplicated by adenosine, which is produced from ATP by the ectonucleotidases CD39 and CD73. Our findings suggest that CD4+CD25+Foxp3+CD39+ Treg cells play an important role in constraining pathogenic Th17 cells and their reduction in multiple sclerosis patients might lead to an inability to control IL-17 mediated autoimmune inflammation.
CD80 Blockade Enhance Glucocorticoid-Induced Leucine Zipper Expression and Suppress Experimental Autoimmune Encephalomyelitis
Authors: Dudhgaonkar Shailesh P. , Janardhanam Srihari B. , Kodumudi Krithika N. , Srinivasan Mythily
Published: November 2009

Designing mimetic of the interface functional groups of known receptor-ligand complexes is an attractive strategy for developing potential therapeutic agents that interfere with target protein-protein interactions. The CD80/CD86-CD28/CD152 costimulatory interactions transmit signals for CD4+ T cell activation and suppression and are critically involved in the initiation, progression, and reactivation of the immunopathology in multiple sclerosis. Differences in the pattern, levels, and kinetics of expression of CD80/CD86 molecules in conjunction with differences in the strength of the signals delivered upon binding CD28 or CD152 determine the outcome of the immune response. A temporal up-regulation of surface expression of CD80 relative to CD86 on APCs and CNS-infiltrating cells has been shown to correlate with disease progression in experimental autoimmune encephalomyelitis an animal model for multiple sclerosis. Hence blockade of the CD80 costimulatory axis has therapeutic potential in multiple sclerosis. In this study, we report the efficacy of a novel CD80-blocking agent CD80-competitive antagonist peptide (CD80-CAP) in suppressing clinical disease and relapse in experimental autoimmune encephalomyelitis. The CD80-CAP mediates protection by inhibiting proinflammatory cytokines and skewing toward anti-inflammatory response presumably by enhancing the expression of glucocorticoid-induced leucine zipper in activated CD4+ T cells.
Cutting Edge: Requirement of MARCH-I-Mediated MHC II Ubiquitination for the Maintenance of Conventional Dendritic Cells
Authors: Ohmura-Hoshino Mari , Matsuki Yohei , Mito-Yoshida Mari , Goto Eiji , Aoki-Kawasumi Masami , Nakayama Manabu , Ohara Osamu , Ishido Satoshi
Published: November 2009

MARCH-I (membrane-associated RING-CH I) has been suggested as a physiological E3 ubiquitin ligase for both MHC class II (MHC II) and B7-2. In this study, we show that MARCH-I-mediated MHC II ubiquitination is necessary for the maintenance of conventional dendritic cell (cDC) functions in the steady state. MARCH-I-deficient cDCs accumulated MHC II and B7-2 and exhibited low Ag-presenting ability for exogenous Ags and low cytokine-producing ability upon stimulation in vivo. Importantly, MHC II, but not B7-2, was required for impaired cDC function induced by loss of MARCH-I in vivo. Moreover, MHC II knockin mice whose MHC II was not ubiquitinated showed dysfunction of cDC similar to that of MARCH-I knockout mice. These results suggest that the accumulation of MHC II resulting from loss of ubiquitination caused cDC abnormality; therefore, MARCH-I may function as a housekeeper of cDC in the steady state.
MAPK, Phosphatidylinositol 3-Kinase, and Mammalian Target of Rapamycin Pathways Converge at the Level of Ribosomal Protein S6 Phosphorylation to Control Metabolic Signaling in CD8 T Cells
Authors: Salmond Robert J. , Emery Juliet , Okkenhaug Klaus , Zamoyska Rose
Published: November 2009

Ribosomal protein S6 (rpS6) is a key component of the translational machinery in eukaryotic cells and is essential for ribosome biogenesis. rpS6 is phosphorylated on evolutionarily conserved serine residues, and data indicate that rpS6 phosphorylation might regulate cell growth and protein synthesis. Studies in cell lines have shown an important role for the serine kinase mammalian target of rapamycin (mTOR) in rpS6 phosphorylation, further linking rpS6 to control of cellular metabolism. rpS6 is essential in T cells because its deletion in mouse double-positive thymocyte cells results in a complete block in T cell development; however, the signaling pathway leading to rpS6 phosphorylation downstream of TCR stimulation has yet to be fully characterized. We show that maximal TCR-induced rpS6 phosphorylation in CD8 T cells requires both Lck and Fyn activity and downstream activation of PI3K, mTOR, and MEK/ERK MAPK pathways. We demonstrate that there is cross-talk between the PI3K and MAPK pathways as well as PI3K-independent mTOR activity, which result in differential phosphorylation of specific rpS6 serine residues. These results place rpS6 phosphorylation as a point of convergence for multiple crucial signaling pathways downstream of TCR triggering.
MAp44, a Human Protein Associated with Pattern Recognition Molecules of the Complement System and Regulating the Lectin Pathway of Complement Activation
Authors: Degn Søren E. , Hansen Annette G. , Steffensen Rudi , Jacobsen Christian , Jensenius Jens C. , Thiel Steffen
Published: November 2009

Essential effector functions of innate immunity are mediated by complement activation initiated by soluble pattern recognition molecules: mannan-binding lectin (MBL) and the ficolins. We present a novel, phylogenetically conserved protein, MAp44, which is found in human serum at 1.4 μg/ml in Ca2+-dependent complexes with the soluble pattern recognition molecules. The affinity for MBL is in the nanomolar range (KD = 0.6 nM) as determined by surface plasmon resonance. The first eight exons of the gene for MAp44 encode four domains shared with MBL-associated serine protease (MASP)-1 and MASP-3 (CUB1-EGF-CUB2-CCP1), and a ninth exon encodes C-terminal 17 aa unique to MAp44. mRNA profiling in human tissues shows high expression in the heart. MAp44 competes with MASP-2 for binding to MBL and ficolins, resulting in inhibition of complement activation. Our results add a novel mechanism to those known to control the innate immune system.
Serine 649 Phosphorylation within the Protein Kinase C-Regulated Domain Down-Regulates CARMA1 Activity in Lymphocytes
Authors: Moreno-García Miguel E. , Sommer Karen , Haftmann Claudia , Sontheimer Clayton , Andrews Sarah F. , Rawlings David J.
Published: November 2009

Phosphorylation of CARMA1 is a crucial event initiating the assembly of IκB kinase and JNK signaling complexes downstream of activated Ag receptors. We previously mapped three protein kinase C (PKC) target sites in murine CARMA1 in vitro, and demonstrated that mutation of two of these serines (S564 and S657) resulted in reduced NF-κB activation, whereas mutation of the third serine (S649) had no clear effect. In this study, we report that when low concentrations of Ag receptor activators are used, loss of S649 (by mutation to alanine) promotes enhanced IκB kinase and JNK activation in both B and T cell lines. Reconstitution of CARMA1−/− DT40 B cells with CARMA1 S649A leads to increased cell death and reduced cell growth in comparison to wild-type CARMA1, likely a result of enhanced JNK activation. To directly determine whether S649 is modified in vivo, we generated phospho-specific Abs recognizing phospho-S649, and phospho-S657 as a positive control. Although phospho-S657 peaked and declined rapidly after Ag receptor stimulation, phospho-S649 occurred later and was maintained for a significantly longer period poststimulation in both B and T cells. Interestingly, phospho-S657 was completely abolished in PKCβ-deficient B cells, whereas delayed phosphorylation at S649 was partially intact and depended, in part, upon novel PKC activity. Thus, distinct PKC-mediated CARMA1 phosphorylation events exert opposing effects on the activation status of CARMA1. We propose that early phosphorylation events at S657 and S564 promote the initial assembly of the CARMA1 signalosome, whereas later phosphorylation at S649 triggers CARMA1 down-regulation.
Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection
Authors: Tate Michelle D. , Deng Yi-Mo , Jones Jessica E. , Anderson Gary P. , Brooks Andrew G. , Reading Patrick C.
Published: November 2009

The clinical response to influenza infection ranges from mild disease to severe pneumonia and it remains unclear whether the inflammatory response to infection is protective or pathogenic. We have defined a novel role for neutrophils in ameliorating lung injury during influenza infection, thereby limiting development of severe disease. Infection of neutrophil-depleted mice with influenza virus HKx31 (H3N2) led to rapid weight loss, pneumonia, and death. Neutropenia was associated with enhanced virus replication in the respiratory tract; however, viral titers were declining at the time of death, leading us to investigate other factors contributing to mortality. In addition to thymic atrophy, lymphopenia, and viremic spread, depletion of neutrophils led to exacerbated pulmonary inflammation, edema, and respiratory dysfunction. Thus, while it is well established that neutrophils contribute to lung injury in a range of pathological conditions, reduced numbers or impaired neutrophil function can facilitate progression of mild influenza to severe clinical disease.
TGFβ Neutralization within Cardiac Allografts by Decorin Gene Transfer Attenuates Chronic Rejection
Authors: Faust Susan M. , Lu Guanyi , Wood Sherri C. , Bishop D. Keith
Published: November 2009

Chronic allograft rejection (CR) is the leading cause of late graft failure following organ transplantation. CR is a progressive disease, characterized by deteriorating graft function, interstitial fibrosis, cardiac hypertrophy, and occlusive neointima development. TGFβ, known for its immunosuppressive qualities, plays a beneficial role in the transplant setting by maintaining alloreactive T cells in a hyporesponsive state, but has also been implicated in promoting graft fibrosis and CR. In the mouse vascularized cardiac allograft model, transient depletion of CD4+ cells promotes graft survival but leads to CR, which is associated with intragraft TGFβ expression. Decorin, an extracellular matrix protein, inhibits both TGFβ bioactivity and gene expression. In this study, gene transfer of decorin into cardiac allografts was used to assess the impact of intragraft TGFβ neutralization on CR, systemic donor-reactive T cell responses, and allograft acceptance. Decorin gene transfer and neutralization of TGFβ in cardiac allografts significantly attenuated interstitial fibrosis, cardiac hypertrophy, and improved graft function, but did not result in systemic donor-reactive T cell responses. Thus, donor-reactive T and B cells remained in a hyporesponsive state. These findings indicate that neutralizing intragraft TGFβ inhibits the cytokine’s fibrotic activities, but does not reverse its beneficial systemic immunosuppressive qualities.
Tyrosine Kinase 2 Plays Critical Roles in the Pathogenic CD4 T Cell Responses for the Development of Experimental Autoimmune Encephalomyelitis
Authors: Oyamada Akiko , Ikebe Hiori , Itsumi Momoe , Saiwai Hirokazu , Okada Seiji , Shimoda Kazuya , Iwakura Yoichiro , Nakayama Keiichi I. , Iwamoto Yukihide , Yoshikai Yasunobu , Yamada Hisakata
Published: November 2009

Tyrosine kinase 2 (Tyk2), a member of the JAK family, is involved in IL-12- and IL-23-mediated signaling. In the present study, we examined the roles of Tyk2 in the development of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) by using Tyk2 knockout (KO) mice. In vitro differentiation of Th1 but not Th17 cells was severely impaired in Tyk2 KO CD4 T cells, although Tyk2 KO Th17 cells did not respond to IL-23. Tyk2 KO mice showed complete resistance against EAE with no infiltration of CD4 T cells in the spinal cord. Surprisingly, the number of MOG-specific Th17 cells in the periphery was comparable between KO and wild-type (WT) mice, whereas Th1 cells were greatly reduced in Tyk2 KO mice. Adoptive transfer of MOG-primed WT T cells induced EAE in Tyk2 KO recipients, indicating that Tyk2 in the environment was dispensable for the infiltration of effector T cells into the spinal cord. A reduced but significant number of Tyk2 KO T cells were detected in the spinal cord of mice with EAE, which had been reconstituted with bone marrow cells of WT and KO mice. Furthermore, MOG-immunized Tyk2 KO mice developed EAE after adoptive transfer of MOG-primed WT Th1 cells, which might trigger local inflammation that recruits Th17 cells. Taken together, these results indicate that Tyk2 is critically involved in the pathogenic CD4 T cell responses and thus could be a target molecule for the treatment of autoimmune diseases.
Immune Gene and Cell Enrichment Is Associated with a Good Prognosis in Ependymoma
Authors: Donson Andrew M. , Birks Diane K. , Barton Valerie N. , Wei Qi , Kleinschmidt-DeMasters Bette K. , Handler Michael H. , Waziri Allen E. , Wang Michael , Foreman Nicholas K.
Published: November 2009

Approximately 50% of children with ependymoma will suffer from tumor recurrences that will ultimately lead to death. Development of more effective therapies and patient stratification in ependymoma mandates better prognostication. In this study, tumor gene expression microarray profiles from pediatric ependymoma clinical samples were subject to ontological analyses to identify outcome-associated biological factors. Histology was subsequently used to evaluate the results of ontological analyses. Ontology analyses revealed that genes associated with nonrecurrent ependymoma were predominantly immune function-related. Additionally, increased expression of immune-related genes was correlated with longer time to progression in recurrent ependymoma. Of those genes associated with both the nonrecurrent phenotype and that positively correlated with time to progression, 95% were associated with immune function. Histological analysis of a subset of these immune function genes revealed that their expression was restricted to a subpopulation of tumor-infiltrating cells. Analysis of tumor-infiltrating immune cells showed increased infiltration of CD4+ T cells in the nonrecurrent ependymomas. No genomic sequences for SV40, BK, JC, or Merkel polyomaviruses were found in nonrecurrent ependymoma. This study reveals that up-regulation of immune function genes is the predominant ontology associated with a good prognosis in ependymoma and it provides preliminary evidence of a beneficial host proinflammatory and/or Ag-specific immune response.
The effect of the lateral interactions on the critical behavior of long straight rigid rods on two-dimensional lattices
Authors: Longone P. , Linares D. H. , Ramirez-Pastor A. J.
Published: November 2009

Using Monte Carlo simulations and finite-size scaling analysis, the critical behavior of attractive rigid rods of length $k$ ($k$-mers) on square lattices at intermediate density has been studied. A nematic phase, characterized by a big domain of parallel $k$-mers, was found. This ordered phase is separated from the isotropic state by a continuous transition occurring at a intermediate density $\theta_c$, which increases linearly with the magnitude of the lateral interactions.Received: 9 July 2009, Accepted: 6 November 2009; Edited by: J. A. Bertolotto; DOI: 10.4279/PIP.010005
Vision-Language Models for Feature Detection of Macular Diseases on Optical Coherence Tomography
Authors: Antaki Fares , Chopra Reena , Keane Pearse A.
Published: May 2024

Importance

Vision-language models (VLMs) are a novel artificial intelligence technology capable of processing image and text inputs. While demonstrating strong generalist capabilities, their performance in ophthalmology has not been extensively studied.

Objective

To assess the performance of the Gemini Pro VLM in expert-level tasks for macular diseases from optical coherence tomography (OCT) scans.

Design, Setting, and Participants

This was a cross-sectional diagnostic accuracy study evaluating a generalist VLM on ophthalmology-specific tasks using the open-source Optical Coherence Tomography Image Database. The dataset included OCT B-scans from 50 unique patients: healthy individuals and those with macular hole, diabetic macular edema, central serous chorioretinopathy, and age-related macular degeneration. Each OCT scan was labeled for 10 key pathological features, referral recommendations, and treatments. The images were captured using a Cirrus high definition OCT machine (Carl Zeiss Meditec) at Sankara Nethralaya Eye Hospital, Chennai, India, and the dataset was published in December 2018. Image acquisition dates were not specified.

Exposures

Gemini Pro, using a standard prompt to extract structured responses on December 15, 2023.

Main Outcomes and Measures

The primary outcome was model responses compared against expert labels, calculating F1 scores for each pathological feature. Secondary outcomes included accuracy in diagnosis, referral urgency, and treatment recommendation. The model’s internal concordance was evaluated by measuring the alignment between referral and treatment recommendations, independent of diagnostic accuracy.

Results

The mean F1 score was 10.7% (95% CI, 2.4-19.2). Measurable F1 scores were obtained for macular hole (36.4%; 95% CI, 0-71.4), pigment epithelial detachment (26.1%; 95% CI, 0-46.2), subretinal hyperreflective material (24.0%; 95% CI, 0-45.2), and subretinal fluid (20.0%; 95% CI, 0-45.5). A correct diagnosis was achieved in 17 of 50 cases (34%; 95% CI, 22-48). Referral recommendations varied: 28 of 50 were correct (56%; 95% CI, 42-70), 10 of 50 were overcautious (20%; 95% CI, 10-32), and 12 of 50 were undercautious (24%; 95% CI, 12-36). Referral and treatment concordance were very high, with 48 of 50 (96%; 95 % CI, 90-100) and 48 of 49 (98%; 95% CI, 94-100) correct answers, respectively.

Conclusions and Relevance

In this study, a generalist VLM demonstrated limited vision capabilities for feature detection and management of macular disease. However, it showed low self-contradiction, suggesting strong language capabilities. As VLMs continue to improve, validating their performance on large benchmarking datasets will help ascertain their potential in ophthalmology.
Prefabricated Fibula Flap vs Bone-Driven and Delayed Implant Installation for Jaw Reconstruction
Authors: Tabet Paul , Bellavance Samuel , Harris Jeffrey R. , Ansari Khalid , Osswald Martin , Nayar Suresh , Seikaly Hadi
Published: May 2024

Importance

Restoration of dental occlusion and oral rehabilitation is the ultimate goal of functional jaw reconstruction.

Objective

To evaluate the prefabricated fibula flap (PFF) technique in occlusion-driven jaw reconstruction for benign or previously treated malignant disease.

Design, Setting, and Participants

This cohort study was conducted from January 2000 to December 2019 at the University of Alberta Hospital and Institute of Reconstructive Sciences in Medicine in Edmonton, Alberta, Canada, among patients who underwent PFF or bone-driven and delayed osseointegrated implant installation (BDD). Patients were followed up for a minimum of 1 year after occlusal rehabilitation. Data were analyzed from July 2021 to June 2022.

Exposures

Patients underwent BDD or PFF, which consists of osseointegrated dental implant installation and skin grafting of the fibular bone 3 to 6 months before jaw tumor resection or defect reconstruction. The implant osseointegration is completed at the time of jaw reconstruction, allowing for full reconstruction, loading, and restoration of the dental occlusion in the immediate postoperative period.

Main outcomes and Measure

Safety, effectiveness, accuracy, timeliness of occlusal reconstruction, and aesthetic appeal were compared between PFF and BDD. Groups were compared for the following variables: postoperative complications, number of bony segments used, number of procedures needed, total operative time, time to occlusal rehabilitation, and number of implants installed, exposed, lost, and used (ie, exposed implants – lost implants). Aesthetic appeal was assessed using standardized full-face and profile digital photographs taken before and 6 to 12 months after the operation and analyzed by 3 naive raters.

Results

Among 9 patients receiving PFF (mean [SD] age, 43.3 [13.0] years; 7 men [77.8%]) and 12 patients receiving BDD (mean [SD] age, 41.9 [18.0] years; 8 men [66.7%]), the overall complication rate was similar (4 patients [44.4%] vs 3 patients [25.0%], respectively; relative risk, 1.78 [95% CI, 0.52 to 6.04]). The number of patients with implant loss was similar between PFF and BDD groups (0 patients vs 3 patients [25.0%], respectively; difference, −25.0 percentage points [95% CI, −48.4 to 9.7 percentage points]). PFF had a clinically meaningful faster mean (SD) occlusal rehabilitation compared with BDD (12.1 [1.9] months vs 60.4 [23.1] months; difference, −48.3 months [95% CI, −64.5 to −32.0 months]). The mean (SD) difference in preoperative to postoperative aesthetic score was similar between PFF and BDD groups (−0.8 [1.5] vs −0.2 [0.8]; difference, −0.6 [95% CI, −1.6 to 0.4]).

Conclusions and Relevance

This study found that PFF compared with BDD was a safe, effective, and aesthetic reconstructive option for patients with benign or previously treated jaw malignant tumors. This technique may provide rapid occlusal reconstruction and oral rehabilitation.
Concurrent Pregnancies and Parental Leaves Among Trainees in a Residency Program
Authors: Noij Kimberley S. , Hillel Alexander T. , Jenks Carolyn M.
Published: May 2024

This Viewpoint shares the experience of a single Otolaryngology−Head & Neck Surgery residency program that faced the scheduling challenges of having nearly a quarter of its residents expecting a child and on parental leave.
Feasibility of patient‐specific quality assurance (PSQA) for real‐time robotic stereotactic body radiotherapy (SBRT) based on tumor motion traces
Authors: Xu Qianyi , Fan Jiajin , Vinogradskiy Yevgeniy , Chawla Ashish K. , Kubicek Gregory , Yang Haihua , Huynh Kiet , LaCouture Tamara , Grimm Jimm , Nie Wei
Published: May 2024

Purpose

To design a patient specific quality assurance (PSQA) process for the CyberKnife Synchrony system and quantify its dosimetric accuracy using a motion platform driven by patient tumor traces with rotation.

Methods

The CyberKnife Synchrony system was evaluated using a motion platform (MODUSQA) and a SRS MapCHECK phantom. The platform was programed to move in the superior‐inferior (SI) direction based on tumor traces. The detector array housed by the StereoPhan was placed on the platform. Extra rotational angles in pitch (head down, 4.0° ± 0.15° or 1.2° ± 0.1°) were added to the moving phantom to examine robot capability of angle correction during delivery. A total of 15 Synchrony patients were performed SBRT PSQA on the moving phantom. All the results were benchmarked by the PSQA results based on static phantom.

Results

For smaller pitch angles, the mean gamma passing rates were 99.75% ± 0.87%, 98.63% ± 2.05%, and 93.11% ± 5.52%, for 3%/1 mm, 2%/1 mm, and 1%/1 mm, respectively. Large discrepancy in the passing rates was observed for different pitch angles due to limited angle correction by the robot. For larger pitch angles, the corresponding mean passing rates were dropped to 93.00% ± 10.91%, 88.05% ± 14.93%, and 80.38% ± 17.40%. When comparing with the static phantom, no significant statistic difference was observed for smaller pitch angles (p = 0.1 for 3%/1 mm), whereas a larger statistic difference was observed for larger pitch angles (p < 0.02 for all criteria). All the gamma passing rates were improved, if applying shift and rotation correction.

Conclusions

The significance of this work is that it is the first study to benchmark PSQA for the CyberKnife Synchrony system using realistically moving phantoms with rotation. With reasonable delivery time, we found it may be feasible to perform PSQA for Synchrony patients with a realistic breathing pattern.
Calculation method for novel upright CT scanner isodose curves
Authors: Kissick Michael W. , Panaino Costanza , Criscuolo Anthony , Hayes John , Hoffman Carson , Mackie Rockwell , Schreuder Andries N.
Published: May 2024

Purpose

A computational method based on Monte‐Carlo calculations is presented and used to calculate isodose curves for a new upright and tilting CT scanner useful for radiation protection purposes.

Methods

The TOPAS code platform with imported CAD files for key components was used to construct a calculation space for the scanner. A sphere of water acts as the patient would by creating scatter out of the bore. Maximum intensity dose maps are calculated for various possible tilt angles to make sure radiation protection for site planning uses the maximum possible dose everywhere.

Results

The resulting maximum intensity isodose lines are more rounded than ones for just a single tilt angle and so closer to isotropic. These maximum intensity curves are closer to the isotropic assumption used in CTDI or DLP based methods of site planning and radiation protection. The isodose lines are similar to those of a standard CT scanner, just tilted upwards. There is more metal above the beam that lessens the dose above versus below isocenter.

Conclusion

Aside from the orientation, this upright scanner is very similar to a typical CT scanner, and nothing different for shielding needs to be done for this new upright tilting CT scanner, because an isotropic scatter source is often assumed for any CT scanner.
Development of a phantom for assessing the precision of setup in skin mark‐less surface‐guided radiotherapy
Authors: Saito Masahide , Ueda Koji , Nemoto Hikaru , Onishi Yoshiko , Suzuki Hidekazu , Suzuki Toshihiro , Sano Naoki , Komiyama Takafumi , Marino Kan , Onishi Hiroshi
Published: May 2024

Background

Surface‐guided radiotherapy (SGRT) is adopted by several institutions; however, reports on the phantoms used to assess the precision of the SGRT setup are limited.

Purpose

The purpose of this study was to develop a phantom to verify the accuracy of the irradiation position during skin mark‐less SGRT.

Methods

An acrylonitrile butadiene styrene (ABS) plastic cube phantom with a diameter of 150 mm on each side containing a dummy target of 15 mm and two types of body surface‐shaped phantoms (breast/face shape) that could be attached to the cube phantom were fabricated. Films can be inserted on four sides of the cubic phantom (left, right, anterior and posterior), and the center of radiation can be calculated by irradiating the dummy target with orthogonal MV beams. Three types of SGRT using a VOXELAN‐HEV600M (Electronics Research&Development Corporation, Okayama, Japan) were evaluated using this phantom: (i) SGRTCT—a SGRT set‐up based solely on a computed tomography (CT)‐reference image. (ii) SGRTCT + CBCT—a method where cone beam computed tomography (CBCT) matching was performed after SGRTCT. (iii) SGRTScan—a resetup technique using a scan reference image obtained after completing the (ii) step.

Results

Both the breast and face phantoms were recognized in the SGRT system without problems. SGRTScan ensure precision within 1 mm/1° for breast and face verification, respectively. All SGRT methods showed comparable rotational accuracies with no significant disparities.

Conclusions

The developed phantom was useful for verifying the accuracy of skin mark‐less SGRT position matching. The SGRTScan demonstrated the feasibility of achieving skin‐mark less SGRT with high accuracy, with deviations of less than 1 mm. Additional research is necessary to evaluate the suitability of the developed phantoms for use in various facilities and systems. This phantom could be used for postal surveys in the future.
Advances in Bioadhesive Hydrogels for Musculoskeletal Tissue Application
Authors: Zhang Fang‐Xue , Chien Meng‐Han , Fan Qing‐rui , Jiang Dong
Published: May 2024

The musculoskeletal system, which is responsible for weight‐bearing, movement, and organ protection, faces many disorders arising from injuries, diseases, and trauma that affect millions of people worldwide, resulting in a decreased quality of life and socioeconomic burden. Tissue engineering is at the forefront of current research on tissue regeneration and demonstrates great potential for musculoskeletal tissue repair. Among the numerous grafts available, adhesive hydrogels have demonstrated potential for tissue applications. Despite the surge in the development of bioadhesive hydrogel formulations in recent years, the absence of an evaluation protocol for their formulation has led to the emergence of numerous similar products that do not fully meet the clinical requirements for applicability in musculoskeletal tissue regeneration. This review aims to address this gap by first discussing the design considerations for an ideal bioadhesive hydrogel relevant to successful musculoskeletal tissue repair. By thoroughly reviewing recent research advances in bioadhesive hydrogels, with a particular focus on their applications in facilitating musculoskeletal tissue repair, improvements are proposed in the current evaluation criteria for the development of novel bioadhesive hydrogels for musculoskeletal tissue applications, and several key challenges and research directions for their implementation are summarized.
Efficient Carbon‐Based Hole‐Conductor‐Free Printable Mesoscopic Perovskite Solar Cells via a Multifunctional Fluorinated Molecule
Authors: Xiang Junwei , Cheng Yanjie , Zhang Guodong , Liu Zhiyang , Han Chuanzhou , Gao Qiaojiao , Wang Chaoyang , Xie Jiayu , Li Shiang , Zhou Zijian , Liu Jing , Lu Xinhui , Mei Anyi , Zhou Yinhua , Han Hongwei
Published: May 2024

Benefiting from their simple and cost‐effective fabrication procedures, printable mesoscopic perovskite solar cells (p‐MPSCs) exhibit substantial potential for large‐scale production. In p‐MPSCs, the thickness of the perovskite filled in the TiO2 and ZrO2 mesoporous layers is ≈3 µm. Therefore, the perovskite crystallization process is more intricate and challenging in the mesoporous structure than the general planar thin film (0.3–0.5 µm). In this work, a multifunctional fluorinated molecule is applied to work as an additive to improve the perovskite crystallization, enhance the device efficiency, and elevate the operational stability. This additive forms robust coordination between its carbonyl groups and uncoordinated Pb2+, thereby effectively passivating defects. The hydrophobic properties of the fluorinated molecule contribute to the device's water‐resistant capability and long‐term operational stability. With these synergistic effects, the power conversion efficiency (PCE) of small‐area cells (0.1 cm2) reaches 20.15% under 1 sun illumination. Large‐area modules (56.4 cm2) are fabricated and exhibit a PCE of 15.41%.
Tensile Control of Vibrational Strong Light‐Matter Coupling with Flexible Polyester Films
Authors: Akinoglu Goekalp Engin , Quan Dali , Rokhsat Eliza , Hutchison James Andell
Published: May 2024

Polaritons are generated by strong interaction between photons and matter, with the hybridization fundamentally changing the energy landscape of the system. Future exploitation of polaritons will benefit from implementing low‐cost, flexible, and easily tuneable configurations, as electronics have before. Here, coherent coupling of the carbonyl stretch vibrations of polyester (poly(ethylene terephthalate), PET) films to the optical modes of a Fabry–Perot (FP) cavity is presented, in which the FP cavity is directly formed on flexible, free‐standing, and commercially available PET films. For 2‐µm thick PET films, the carbonyl stretch vibration of the PET overlaps with the half‐wavelength FP cavity mode, leading to the coupling of the two modes, a Rabi splitting above 160 cm−1, and associated anticrossing in angular dispersion measurements. The study demonstrates dynamic control of light‐matter interaction strength by modulating film thickness under tension, finding that a 25% tensile stretch can tune the light‐matter interaction from 20:80 mixing to near‐perfect 50:50 hybridization at normal incidence. These findings are discussed in the context of future foldable/twistable/wearable polaritonic devices.
Critical Factors Contributing to the Thermal Runaway of Thiophosphate Solid Electrolytes for All‐Solid‐State Batteries
Authors: Kim Taehun , Chang Hongjun , Song Gawon , Lee Suyeon , Kim Kanghyeon , Lee Seonghyun , Moon Janghyuk , Lee Kyu Tae
Published: May 2024

Although all‐solid‐state batteries are suggested as a means to tackle the safety concerns associated with current Li‐ion batteries, there is presently a lack of comprehensive understanding regarding their thermal safety. In this context, critical factors contributing to the thermal runaway of thiophosphate solid electrolytes with charged Li1‐xNi0.8Co0.1Mn0.1O2 (NCM) under thermal and mechanical abuse conditions are demonstrated, considering parameters such as heating rate under thermal abuse conditions and the hybridization of S atom in structure. In particular, the thermal behavior of various solid electrolytes, including thiophosphates, thioantimonates, and halides, is investigated to clarify critical elements in Li6PS5Cl (LPSCl) contributing to its thermal instability when combined with charged NCM. Various ex situ analyses, along with density functional theory calculations, reveal a correlation between the hybridization of S atoms and the thermal instability of solid electrolytes, suggesting that sulfur acts as a key element triggering the thermal runaway of sulfide‐based solid electrolytes.
Water‐Mediated On‐Demand Detachable Solid‐State Adhesive of Porous Hydroxyapatite for Internal Organ Retractions
Authors: Okada Masahiro , Xie Shi Chao , Kobayashi Yusuke , Yanagimoto Hiroaki , Tsugawa Daisuke , Tanaka Masaru , Nakano Takayoshi , Fukumoto Takumi , Matsumoto Takuya
Published: May 2024

Novel adhesives for biological tissues offer an advanced surgical approach. Here, the authors report the development and application of solid‐state adhesives consisting of porous hydroxyapatite (HAp) biocompatible ceramics as novel internal organ retractors. The operational principles of the porous solid‐state adhesives are experimentally established in terms of water migration from biological soft tissues into the pores of the adhesives, and their performance is evaluated on several soft tissues with different hydration states. As an example of practical medical utility, HAp adhesive devices demonstrate the holding ability of porcine livers and on‐demand detachability in vivo, showing great potential as internal organ retractors in laparoscopic surgery.
Water‐Responsive Self‐Contractive Silk‐Based Skin Anti‐Aging Tensioners with Customizable Biofunctions
Authors: Xie Yating , Geng Lele , Ni Siyuan , Ni Wei , He Ruizhe , Liu Tiantian , Zhang Gai , Tao Tiger H. , Liu Keyin , Peng Yinbo
Published: May 2024

Skin anti‐aging treatments have become increasingly popular. Currently, the prevalent treatment method involves implanting skin tension regulation threads (skin lifting threads) under the skin, and radiofrequency treatments. In this study, inspired by the natural supercontraction of spider silk, the molecular structure of silk fibroin fibers is modulated into an oriented configuration. This modification endows silk proteins with water‐responsive self‐contraction capabilities, leading to the development of innovative self‐contracting silk‐based skin tensioners (SSSTs). To align with clinical requirements, skin tension regulation materials are functionalized by testing for their self‐contraction, near‐infrared laser heating function, and bacteriostatic properties. The SSSTs exhibited remarkable self‐contraction properties, drug‐loading and sustained‐release capabilities, notable antibacterial effects, controllable degradation, and good biocompatibility. Moreover, the near‐infrared light heating function effectively increased subcutaneous temperature, demonstrating its potential for enhancing and prolonging skin lifting effects. Therefore, SSSTs can be applied for skin tension regulation to improve and delay skin aging. The results may pave the way for novel strategies in skin rejuvenation, with broad implications for the field of skin anti‐aging.
Single‐Step Control of Liquid–Liquid Crystalline Phase Separation by Depletion Gradients
Authors: Lin Dongdong , Bagnani Massimo , Almohammadi Hamed , Yuan Ye , Zhao Yufen , Mezzenga Raffaele
Published: May 2024

Fine‐tuning nucleation and growth of colloidal liquid crystalline (LC) droplets, also known as tactoids, is highly desirable in both fundamental science and technological applications. However, the tactoid structure results from the trade‐off between thermodynamics and nonequilibrium kinetics effects, and controlling liquid–liquid crystalline phase separation (LLCPS) in these systems is still a work in progress. Here, a single‐step strategy is introduced to obtain a rich palette of morphologies for tactoids formed via nucleation and growth within an initially isotropic phase exposed to a gradient of depletants. The simultaneous appearance is shown of rich LC structures along the depleting potential gradient, where the position of each LC structure is correlated with the magnitude of the depleting potential. Changing the size (nanoparticles) or the nature (polymers) of the depleting agent provides additional, precise control over the resulting LC structures through a size‐selective mechanism, where the depletant may be found both within and outside the LC droplets. The use of depletion gradients from depletants of varying sizes and nature offers a powerful toolbox for manipulation, templating, imaging, and understanding heterogeneous colloidal LC structures.
Side Reactions/Changes in Lithium‐Ion Batteries: Mechanisms and Strategies for Creating Safer and Better Batteries
Authors: Du Hao , Wang Yadong , Kang Yuqiong , Zhao Yun , Tian Yao , Wang Xianshu , Tan Yihong , Liang Zheng , Wozny John , Li Tao , Ren Dongsheng , Wang Li , He Xiangming , Xiao Peitao , Mao Eryang , Tavajohi Naser , Kang Feiyu , Li Baohua
Published: May 2024

Lithium‐ion batteries (LIBs), in which lithium ions function as charge carriers, are considered the most competitive energy storage devices due to their high energy and power density. However, battery materials, especially with high capacity undergo side reactions and changes that result in capacity decay and safety issues. A deep understanding of the reactions that cause changes in the battery's internal components and the mechanisms of those reactions is needed to build safer and better batteries. This review focuses on the processes of battery failures, with voltage and temperature as the underlying factors. Voltage‐induced failures result from anode interfacial reactions, current collector corrosion, cathode interfacial reactions, overcharge, and over‐discharge, while temperature‐induced failure mechanisms include SEI decomposition, separator damage, and interfacial reactions between electrodes and electrolytes. The review also presents protective strategies for controlling these reactions. As a result, the reader is offered a comprehensive overview of the safety features and failure mechanisms of various LIB components.