bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher risk for chronic graft‐versus‐host disease (GvHD) in HLA‐G mismatched transplants following allogeneic hematopoietic stem cell transplantation: A retrospective study
Authors: Neuchel Christine , Gowdavally Sowmya , Tsamadou Chrysanthi , Platzbecker Uwe , Sala Elisa , Wagner‐Drouet Eva , Valerius Thomas , Kröger Nicolaus , Wulf Gerald , Einsele Hermann , Thurner Lorenz , Schaefer‐Eckart Kerstin , Freitag Sebastian , Casper Jochen , Dürholt Mareike , Kaufmann Martin , Hertenstein Bernd , Klein Stefan , Ringhoffer Mark , Frank Sandra , Amann Elisa Maria , Rode Immanuel , Schrezenmeier Hubert , Mytilineos Joannis , Fürst Daniel 
Published: July 2022

IntroductionGraft‐versus‐host disease (GvHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo‐HSCT) and is highly influenced by the degree of HLA matching between recipient and donor. The HLA‐class Ib molecule HLA‐G has been shown to promote tolerogenicity through its interaction with inhibitory receptors found on several immunocompetent cells. We hypothesized that in an allo‐HSCT setting, HLA‐G mismatches may negatively impact the HLA‐G‐mediated tolerogenicity either due to inefficient interaction with the inhibitory receptors of the transplanted immune cells or due to direct allorecognition of mismatched HLA‐G on host cells by the immune cells of the donor.MethodsIn order to explore this hypothesis, we investigated the impact of HLA‐G mismatching in 2.083 10/10 matched high resolution HLA‐typed allo‐HSCT transplants.ResultsWe found that the risk of chronic GvHD was significantly higher in HLA‐G‐mismatched transplant cases as compared with the HLA‐G‐matched control group (HR: 1.46, 95%CI = 1.11–1.91, p = 0.006). Sub‐analysis of the mismatch vector revealed that this effect was only detectable in the GvH (HR: 1.89, 95%CI 1.39–2.57, p < 0.001) but not the HvG direction (HR: 1.01, 95%CI = 0.63–1.63, p = 0.967). In addition, the negative impact of HLA‐G mismatching on chronic GvHD was only significant in younger patients (<30y HR: 3.02, 95%CI = 1.25–7.28, p = 0.014; >29y HR: 1.28, 95%CI = 0.94–1.72, p = 0.113).DiscussionOur results indicate that HLA‐G mismatches may contribute to the onset of chronic GvHD, especially in younger patients and should therefore be avoided when possible.
Late Cretaceous geodynamics of the Palaeo‐Pacific plate inferred from basin inversion structures in the Songliao Basin (NE China)
Authors: Qiu Liang , Yan Dan‐Ping , Ma Hongbin , Sun Shouheng , Deng Hongling , Zhou Zhicheng , Zhu Jichang , Zhang Qihui , Shi Haitao , Wang Xin 
Published: July 2022

AbstractReconstructing the process of plate subduction is challenging, but clues can be found in sedimentary basins and the nature of deformation of the overriding plate. Here we analyse a seismic‐reflection dataset that indicates tectonic inversion in the southwestern Songliao basin, NE China, to construct the geodynamics of Palaeo‐Pacific plate. The study area consists of Lower Cretaceous rift sediments that were cut by normal faults, folded, and subsequently overlain by undeformed Upper Cretaceous strata, revealing a process of basin inversion. The timing of inversion is constrained to the interval between deposition of the Lower and Upper Cretaceous sediments (i.e. 87–71 Ma). Mud volcanoes and similar structures associated with inversion are observed in basins throughout the region. The change from tectonic extension to shortening in the overriding plate is recorded by sedimentation and inversion of the basins, and was triggered by an increase in the rate of motion of the subducting Palaeo‐Pacific plate.
Implementation of the Elrod Algorithm in Practical Design of an Axial Lubricant Supply Groove in Journal Bearings
Authors: Wei Shanshan , Groper Morel 
Published: July 2022

Abstract
The Elrod algorithm was implemented to study the effects of axial lubricant supply groove parameters, i.e., groove length, width, and location, on the performance of a one-axial groove journal bearing, taking into consideration thermal effects. The results and presented recommendations will assist bearing designers in determining the groove’s preferred angular location and main dimensions to achieve a solution in terms of low total power loss and high minimum film thickness. It is suggested that with regard to low total power loss and high minimum film thickness, for a lighter loaded bearing, the axial groove should be located in the angular range of 100–140 deg to the load line with a groove length ratio Lg/L over 0.6 or the angular range of 300–350 deg with an Lg/L over 0.75. For a heavier loaded bearing, it is suggested that the groove be placed at the angular range of 80–115 deg with an Lg/L over 0.6.
Methionine deficiency facilitates antitumour immunity by altering m6A methylation of immune checkpoint transcripts
Authors: Li Ting , Tan Yue-Tao , Chen Yan-Xing , Zheng Xiao-Jun , Wang Wen , Liao Kun , Mo Hai-Yu , Lin Junzhong , Yang Wei , Piao Hai-Long , Xu Rui-Hua , Ju Huai-Qiang 
Published: July 2022

ObjectiveMethionine metabolism is involved in a myriad of cellular functions, including methylation reactions and redox maintenance. Nevertheless, it remains unclear whether methionine metabolism, RNA methylation and antitumour immunity are molecularly intertwined.DesignThe antitumour immunity effect of methionine-restricted diet (MRD) feeding was assessed in murine models. The mechanisms of methionine and YTH domain-containing family protein 1 (YTHDF1) in tumour immune escape were determined in vitro and in vivo. The synergistic effects of MRD or YTHDF1 depletion with PD-1 blockade were also investigated.ResultsWe found that dietary methionine restriction reduced tumour growth and enhanced antitumour immunity by increasing the number and cytotoxicity of tumour-infiltrating CD8+T cells in different mouse models. Mechanistically, the S-adenosylmethionine derived from methionine metabolism promoted the N6-methyladenosine (m6A) methylation and translation of immune checkpoints, including PD-L1 and V-domain Ig suppressor of T cell activation (VISTA), in tumour cells. Furthermore, MRD or m6A-specific binding protein YTHDF1 depletion inhibited tumour growth by restoring the infiltration of CD8+T cells, and synergised with PD-1 blockade for better tumour control. Clinically, YTHDF1 expression correlated with poor prognosis and immunotherapy outcomes for cancer patients.ConclusionsMethionine and YTHDF1 play a critical role in anticancer immunity through regulating the functions of T cells. Targeting methionine metabolism or YTHDF1 could be a potential new strategy for cancer immunotherapy.
Chimeric antigen receptor T-cells targeting IL-1RAP: a promising new cellular immunotherapy to treat acute myeloid leukemia
Authors: Trad Rim , Warda Walid , Alcazer Vincent , Neto da Rocha Mathieu , Berceanu Ana , Nicod Clémentine , Haderbache Rafik , Roussel Xavier , Desbrosses Yohan , Daguindau Etienne , Renosi Florain , Roumier Christophe , Bouquet Lucie , Biichle Sabeha , Guiot Melanie , Seffar Evan , Caillot Denis , Depil Stephane , Robinet Eric , Salma Yahya , Deconinck Eric , Deschamps Marina , Ferrand Christophe 
Published: July 2022

BackgroundAcute myeloid leukemia (AML) remains a very difficult disease to cure due to the persistence of leukemic stem cells (LSCs), which are resistant to different lines of chemotherapy and are the basis of refractory/relapsed (R/R) disease in 80% of patients with AML not receiving allogeneic transplantation.MethodsIn this study, we showed that the interleukin-1 receptor accessory protein (IL-1RAP) protein is overexpressed on the cell surface of LSCs in all subtypes of AML and confirmed it as an interesting and promising target in AML compared with the most common potential AML targets, since it is not expressed by the normal hematopoietic stem cell. After establishing the proof of concept for the efficacy of chimeric antigen receptor (CAR) T-cells targeting IL-1RAP in chronic myeloid leukemia, we hypothesized that third-generation IL-1RAP CAR T-cells could eliminate AML LSCs, where the medical need is not covered.ResultsWe first demonstrated that IL-1RAP CAR T-cells can be produced from AML T-cells at the time of diagnosis and at relapse. In vitro and in vivo, we showed the effectiveness of IL-1RAP CAR T-cells against AML cell lines expressing different levels of IL-1RAP and the cytotoxicity of autologous IL-1RAP CAR T-cells against primary cells from patients with AML at diagnosis or at relapse. In patient-derived relapsed AML xenograft models, we confirmed that IL-1RAP CAR T-cells are able to circulate in peripheral blood and to migrate in the bone marrow and spleen, are cytotoxic against primary AML cells and increased overall survival.ConclusionIn conclusion, our preclinical results suggest that IL-1RAP CAR T-based adoptive therapy could be a promising strategy in AML treatment and it warrants the clinical investigation of this CAR T-cell therapy.
Aneurysm treatment with the Woven EndoBridge (WEB) device in the combined population of two prospective, multicenter series: 5-year follow-up
Authors: Pierot Laurent , Szikora Istvan , Barreau Xavier , Holtmannspoetter Markus , Spelle Laurent , Klisch Joachim , Herbreteau Denis , Costalat Vincent , Fiehler Jens , Januel Anne-Christine , Liebig Thomas , Stockx Luc , Weber Werner , Berkefeld Joachim , Moret Jacques , Molyneux Andy , Byrne James 
Published: July 2022

BackgroundEvaluating a new endovascular treatment for intracranial aneurysms must not only demonstrate short-term safety and efficacy, but also evaluate longer-term outcomes (eg, delayed complications, anatomical results, retreatment). The current analysis reports the 5-year clinical and anatomical results of Woven EndoBridge (WEB) treatment in two European combined trial populations (WEBCAST (WEB Clinical Assessment of Intrasaccular Aneurysm Therapy) and WEBCAST-2).MethodsAll adverse events occurring between the procedure and 5-year follow-up were independently evaluated by an expert. Aneurysm occlusion was evaluated by an independent core laboratory using a three-grade scale: complete occlusion, neck remnant, and aneurysm remnant. In cases where data were not available at 5-year follow-up, the last observation carry forward (LOCF) method was used.ResultsThe safety and efficacy populations comprised 100 patients and 95 aneurysms, respectively. No adverse event related to the device occurred after the procedure during the 5-year follow-up period. Mortality at 5 years was 7.0% (7/100 patients) including mortality related to the WEB (0/100, 0.0%), the procedure (1/100, 1.0%), and another condition (6/100, 6.0%). At 5 years, complete aneurysm occlusion was observed in 49/95 (51.6%) aneurysms, neck remnant in 25/95 (26.3%), and aneurysm remnant in 21/95 (22.1%). Retreatment rate at 5 years was 11.6% (11/95 aneurysms).ConclusionsThis analysis conducted in a population of patients with wide-neck bifurcation aneurysms confirms WEB’s safety profile. Additional evidence demonstrates good stability of aneurysm occlusion with adequate occlusion (complete occlusion or neck remnant) at 5 years in 77.9% of aneurysms with a low retreatment rate (11.6%).Clinical trial registrationWEBCAST and WEBCAST-2: Unique identifier:NCT01778322.
Preoperative tumor embolization prolongs time to recurrence of meningiomas: a retrospective propensity-matched analysis
Authors: Akimoto Taisuke , Ohtake Makoto , Miyake Shigeta , Suzuki Ryosuke , Iida Yu , Shimohigoshi Wataru , Higashijima Takefumi , Nakamura Taishi , Shimizu Nobuyuki , Kawasaki Takashi , Sakata Katumi , Yamamoto Tetsuya 
Published: July 2022

BackgroundMeningiomas are often embolized preoperatively to reduce intraoperative blood loss and facilitate tumor resection. However, the procedure is controversial and its effects have not yet been reported. We evaluated preoperative embolization for meningiomas and its effect on postoperative outcome and recurrence.MethodsWe retrospectively reviewed the medical records of 186 patients with WHO grade I meningiomas who underwent surgical treatment at our hospital between January 2010 and December 2020. We used propensity score matching to generate embolization and no-embolization groups (42 patients each) to examine embolization effects.ResultsPreoperative embolization was performed in 71 patients (38.2%). In the propensity-matched analysis, the embolization group showed favorable recurrence-free survival (RFS) (mean 49.4 vs 24.1 months; Wilcoxon p=0.049). The embolization group had significantly less intraoperative blood loss (178±203 mL vs 221±165 mL; p=0.009) and shorter operation time (5.6±2.0 hours vs 6.8±2.8 hours; p=0.036). There were no significant differences in Simpson grade IV resection (33.3% vs 28.6%; p=0.637) or overall perioperative complications (21.4% vs 11.9%; p=0.241). Tumor embolization prolonged RFS in a subanalysis of cases who experienced recurrence (n=39) among the overall cases before variable control (mean RFS 33.2 vs 16.0 months; log-rank p=0.003).ConclusionsAfter controlling for variables, preoperative embolization for meningioma did not improve the Simpson grade or patient outcomes. However, it might have effects outside of surgical outcomes by prolonging RFS without increasing complications.
Role of vertebral corner inflammation and fat deposition on MRI on syndesmophyte development detected on whole spine low-dose CT scan in radiographic axial spondyloarthritis
Authors: Stal Rosalinde , Baraliakos Xenofon , van der Heijde Désirée , van Gaalen Floris , Ramiro Sofia , van den Berg Rosaline , Reijnierse Monique , Braun Juergen , Landewé Robert , Sepriano Alexandre 
Published: July 2022

ObjectivesTo investigate the associations between MRI detected vertebral corner inflammation (VCI) and vertebral corner fat deposition (VCFD) on whole spine low-dose CT scan (ldCT) detected syndesmophyte formation and growth.MethodsPatients from the Sensitive Imaging in Ankylosing Spondylitis cohort underwent MRI (baseline, 1 year and 2 years) and ldCT (baseline and 2 years). MR images were scored by three readers for VCI and VCFD, MRI patterns were defined by presence of VCI and/or VCFD over 2 years. LdCT images were scored by two central readers for presence and size of syndesmophytes and change was calculated for new or new/grown syndesmophytes. Multilevel generalised estimated equations were used to test the associations between VCI and VCFD and syndesmophyte development.ResultsFifty radiographic patients with axial spondyloarthritis were included (mean age 49 years, 86% male, 78% HLA-B27+). Absence of both VCI and VCFD protected against syndesmophyte development (ORs 0.36–0.37). Presence of VCI and/or VCFD increased the risk of syndesmophyte development (ORs 1.73–2.60). Out of all corners with a new or new/grown syndesmophyte, 47% of corners according to reader 1 and 44% according to reader 2 had neither VCI nor VCFD preceding the bone formation.ConclusionsVCI and VCFD were positively associated with syndesmophyte development. This has been shown for the first time for syndesmophytes detected on ldCT and also in the thoracic spine. However, almost half of all bone formation occurred in corners without VCI or VCFD, suggesting the presence of these lesions in yearly MRIs does not fully clarify the development of syndesmophytes.
Efficient Correction of Oncogenic KRAS and TP53 Mutations through CRISPR Base Editing
Authors: Sayed Shady , Sidorova Olga A. , Hennig Alexander , Augsburg Martina , Cortés Vesga Catherine P. , Abohawya Moustafa , Schmitt Lukas T. , Sürün Duran , Stange Daniel E. , Mircetic Jovan , Buchholz Frank 
Published: July 2022

Abstract

KRAS is the most frequently mutated oncogene in human cancer, and its activating mutations represent long-sought therapeutic targets. Programmable nucleases, particularly the CRISPR-Cas9 system, provide an attractive tool for genetically targeting KRAS mutations in cancer cells. Here, we show that cleavage of a panel of KRAS driver mutations suppresses growth in various human cancer cell lines, revealing their dependence on mutant KRAS. However, analysis of the remaining cell population after long-term Cas9 expression unmasked the occurence of oncogenic KRAS escape variants that were resistant to Cas9-cleavage. In contrast, the use of an adenine base editor to correct oncogenic KRAS mutations progressively depleted the targeted cells without the appearance of escape variants and allowed efficient and simultaneous correction of a cancer-associated TP53 mutation. Oncogenic KRAS and TP53 base editing was possible in patient-derived cancer organoids, suggesting that base editor approaches to correct oncogenic mutations could be developed for functional interrogation of vulnerabilities in a personalized manner for future precision oncology applications.

Significance:
Repairing KRAS mutations with base editors can be used for providing a better understanding of RAS biology and may lay the foundation for improved treatments for KRAS-mutant cancers.
Updated Efficacy Outcomes of Anti-PD-1 Antibodies plus Multikinase Inhibitors for Patients with Advanced Gastric Cancer with or without Liver Metastases in Clinical Trials
Authors: Yukami Hiroki , Kawazoe Akihito , Lin Yi-Tzu , Koyama Shohei , Fukuoka Shota , Hara Hiroki , Takahashi Naoki , Kojima Takashi , Asayama Masako , Yoshii Takako , Bando Hideaki , Kotani Daisuke , Nakamura Yoshiaki , Kuboki Yasutoshi , Mishima Saori , Wakabayashi Masashi , Kuwata Takeshi , Goto Masahiro , Higuchi Kazuhide , Yoshino Takayuki , Doi Toshihiko , Nishikawa Hiroyoshi , Shitara Kohei 
Published: July 2022

Abstract

Purpose:
We previously reported preliminary activity of regorafenib plus nivolumab (REGONIVO) or lenvatinib plus pembrolizumab (LENPEM) in advanced gastric cancer (AGC). Meanwhile, several studies demonstrated liver metastases are less responsive to immunotherapy.

Patients and Methods:
Combined efficacy outcomes with a longer follow-up in a phase Ib trial of REGONIVO and a phase II trial of LENPEM were examined in AGC with or without liver metastases (REGONIVO plus LENPEM cohort). We also investigated the efficacy of anti-PD-1 monotherapies (anti-PD-1 monotherapy cohort). A comparison of the immune microenvironment between gastric primary tumors and liver metastases was also conducted by multiplex IHC.

Results:
In the REGONIVO plus LENPEM cohort, with a median follow-up of 14.0 months, objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) were 46%, 7.8 months, and 15.6 months in patients with liver metastases, while 69%, 6.9 months, and 15.5 months in those without. In the anti-PD-1 monotherapy cohort, with a median follow-up of 27.6 months, ORR, mPFS, and mOS were 9%, 1.4 months, and 6.4 months in patients with liver metastases, while 22%, 2.3 months, and 9.0 months in those without. Multiplex IHC revealed liver metastases were associated with an abundance of immune-suppressive cells, such as tumor-associated macrophages and regulatory T cells, with fewer CD8+ T cells compared with gastric primary tumors.

Conclusions:
Anti-PD-1 antibodies plus regorafenib or lenvatinib for AGC showed promising antitumor activity with a longer follow-up, irrespective of liver metastases status, despite a more immune-suppressive tumor microenvironment in liver metastases.
CD8+ T-cell Responses Are Boosted by Dual PD-1/VEGFR2 Blockade after EGFR Inhibition in Egfr-Mutant Lung Cancer
Authors: Nishii Kazuya , Ohashi Kadoaki , Tomida Shuta , Nakasuka Takamasa , Hirabae Atsuko , Okawa Sachi , Nishimura Jun , Higo Hisao , Watanabe Hiromi , Kano Hirohisa , Ando Chihiro , Makimoto Go , Ninomiya Kiichiro , Kato Yuka , Kubo Toshio , Ichihara Eiki , Hotta Katsuyuki , Tabata Masahiro , Toyooka Shinichi , Udono Heiichiro , Maeda Yoshinobu , Kiura Katsuyuki 
Published: July 2022

Abstract

Epidermal growth factor receptor (EGFR) is the most frequently mutated driver oncogene in nonsmoking-related, non–small cell lung cancer (NSCLC). EGFR-mutant NSCLC has a noninflamed tumor microenvironment (TME), with low infiltration by CD8+ T cells and, thus, immune-checkpoint inhibitors, such as antiprogrammed cell death-1 (anti–PD-1), have weak antitumor effects. Here, we showed that CD8+ T-cell responses were induced by an EGFR-tyrosine kinase inhibitor (TKI) in syngeneic Egfr-mutant NSCLC tumors, which was further pronounced by the sequential dual blockade of PD-1 and vascular endothelial growth factor receptor 2 (VEGFR2). However, the simultaneous triple blockade had no such effect. The PD-1/VEGFR2 dual blockade did not exert tumor-inhibitory effects without pretreatment with the EGFR-TKI, suggesting that the treatment schedule is crucial for the efficacy of the dual blockade therapy. Pretreatment with EGFR-TKI increased the CD8+ T-cell/regulatory T-cell (Treg) ratio, while also increasing the expression of immunosuppressive chemokines and chemokine receptors, as well as increasing the number of M2-like macrophages, in the TME. Discontinuing EGFR-TKI treatment reversed the transient increase of immunosuppressive factors in the TME. The subsequent PD-1/VEGFR2 inhibition maintained increased numbers of infiltrating CD8+ T cells and CD11c+ dendritic cells. Depletion of CD8+ T cells in vivo abolished tumor growth inhibition by EGFR-TKI alone and the sequential triple therapy, suggesting that EGFR inhibition is a prerequisite for the induction of CD8+ T-cell responses. Our findings could aid in developing an alternative immunotherapy strategy in patients with cancers that have driver mutations and a noninflamed TME.
Direct T-cell Presentation by cDC1: The Key Feature for Cancer Vaccine Success?
Authors: Hubert Margaux , Caux Christophe , Valladeau-Guilemond Jenny 
Published: July 2022

AbstractIn this issue of Cancer Immunology Research, Ferris and colleagues demonstrate that type 1 conventional DC (cDC1) vaccines drive tumor rejection through direct antigen presentation, without the need of endogenous cDC1. This suggests that cDC1-based vaccines could represent an optimal strategy to induce antitumor immunity in patients.See related article by Ferris et al., p. 920 (7) .