bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene network-based and ensemble modeling-based selection of tumor-associated antigens with a predicted low risk of tissue damage for targeted immunotherapy
Authors: Lischer Christopher , Eberhardt Martin , Flamann Cindy , Berges Johannes , Güse Esther , Wessely Anja , Weich Adrian , Retzlaff Jimmy , Dörrie Jan , Schaft Niels , Wiesinger Manuel , März Johannes , Schuler-Thurner Beatrice , Knorr Harald , Gupta Shailendra , Singh Krishna Pal , Schuler Gerold , Heppt Markus Vincent , Koch Elias Andreas Thomas , van Kleef Nadine D , Freen-van Heeren Julian J , Turksma Annelies W , Wolkenhauer Olaf , Hohberger Bettina , Berking Carola , Bruns Heiko , Vera Julio 
Published: May 2024

BackgroundTumor-associated antigens and their derived peptides constitute an opportunity to design off-the-shelf mainline or adjuvant anti-cancer immunotherapies for a broad array of patients. A performant and rational antigen selection pipeline would lay the foundation for immunotherapy trials with the potential to enhance treatment, tremendously benefiting patients suffering from rare, understudied cancers.MethodsWe present an experimentally validated, data-driven computational pipeline that selects and ranks antigens in a multipronged approach. In addition to minimizing the risk of immune-related adverse events by selecting antigens based on their expression profile in tumor biopsies and healthy tissues, we incorporated a network analysis-derived antigen indispensability index based on computational modeling results, and candidate immunogenicity predictions from a machine learning ensemble model relying on peptide physicochemical characteristics.ResultsIn a model study of uveal melanoma, Human Leukocyte Antigen (HLA) docking simulations and experimental quantification of the peptide–major histocompatibility complex binding affinities confirmed that our approach discriminates between high-binding and low-binding affinity peptides with a performance similar to that of established methodologies. Blinded validation experiments with autologous T-cells yielded peptide stimulation-induced interferon-γ secretion and cytotoxic activity despite high interdonor variability. Dissecting the score contribution of the tested antigens revealed that peptides with the potential to induce cytotoxicity but unsuitable due to potential tissue damage or instability of expression were properly discarded by the computational pipeline.ConclusionsIn this study, we demonstrate the feasibility of the de novo computational selection of antigens with the capacity to induce an anti-tumor immune response and a predicted low risk of tissue damage. On translation to the clinic, our pipeline supports fast turn-around validation, for example, for adoptive T-cell transfer preparations, in both generalized and personalized antigen-directed immunotherapy settings.
Targeting NKG2D ligands in glioblastoma with a bispecific T-cell engager is augmented with conventional therapy and enhances oncolytic virotherapy of glioma stem-like cells
Authors: Baugh Richard , Khalique Hena , Page Emma , Lei-Rossmann Janet , Wan Peter Kok-Ting , Johanssen Timothy , Ebner Daniel , Ansorge Olaf , Seymour Leonard W 
Published: May 2024

BackgroundGlioblastoma (GBM) almost invariably becomes resistant towards conventional treatment of radiotherapy and temozolomide (TMZ) chemotherapy, partly due to subpopulations of intrinsically resistant glioma stem-like cells (GSC). The oncolytic herpes simplex virus-1 G207 is a promising approach for GBM virotherapy although its efficacy in patients with GBM is often limited. Natural killer group 2 member D ligands (NKG2DLs) are minimally expressed by healthy cells but are upregulated by the DNA damage response (DDR) and in malignant cells with chronic DDR signaling, resulting in innate immune activation.MethodsWe have designed a bispecific T-cell engager (BiTE) capable of cross-linking CD3 on T cells with NKG2DL-expressing GBM cells. We then engineered the G207 virus to express the NKG2D BiTE and secrete it from infected cells. The efficacy of the free BiTE and BiTE delivered by G207 was evaluated in combination with conventional therapies in GBM cells and against patient-derived GSCs in the context of T-cell activation and target cell viability.ResultsNKG2D BiTE-mediated cross-linking of GBM cells and T cells causes antigen-independent T-cell activation, pro-inflammatory cytokine release, and tumor cell death, thereby combining direct viral oncolysis with BiTE-mediated cytotoxicity. Surface NKG2DL expression was further elevated on GBM cells following pretreatment with sublethal doses of TMZ and radiation to induce the DDR, increasing sensitivity towards G207-NKG2D BiTE and achieving synergistic cytotoxicity. We also demonstrate a novel strategy for targeting GSCs that are non-permissive to G207 infection but remain sensitive to NKG2D BiTE.ConclusionsWe propose a potential model for targeting GSCs in heterogeneous tumors, whereby differentiated GBM cells infected with G207-NKG2D BiTE produce NKG2D BiTE locally, directing T-cell cytotoxicity towards the GSC subpopulations in the tumor microenvironment.
Prospective open-label trial with rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy not responding to conventional immune therapies
Authors: Doneddu Pietro Emiliano , Cocito Dario , Fazio Raffaella , Benedetti Luana , Peci Erdita , Liberatore Giuseppe , Falzone Yuri Matteo , Germano Francesco , Gallia Francesca , Giannotta Claudia , Lleixà Cinta , Bianchi Elisa , Nobile-Orazio Eduardo 
Published: May 2024

BackgroundTo evaluate the efficacy of rituximab in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients not responding to conventional immune therapies.MethodsAn open-label, prospective exploratory study was conducted with intravenous rituximab on 17 CIDP patients who had not responded to at least two first-line therapies. The primary endpoint was to determine the proportion of patients who showed improvement 6 months after rituximab therapy. The percentage of responders to rituximab, along with a 95% CI, was reported and compared with the 30% response rate after other immunosuppressive drugs previously documented in the literature.Results13 of the 17 treated patients (76.5%) showed improvement at 6 months (95% CI 50.1 to 93.2). Among the 14 patients who completed the 12-month follow-up (2 were lost to follow-up after showing improvement at months 8 and 10, and 1 deteriorated at 6 months), 13 (92.9%) demonstrated improvement at 12 months (95% CI 66.1 to 99.8). Nerve conduction parameters improved by at least 20% in two nerves in 6 out of 15 (40%) patients at 6 months and in 7 out of 13 (53.9%) at 12 months. None of the treated patients withdrew from the study due to side effects. There was a significant reduction of circulating CD19+ cells 15 days, 2, 6 and 12 months after treatment.ConclusionRituximab seems to be a safe therapy in most patients with CIDP not responding to conventional immune therapies. The high percentage of patients who improved in this study suggests a possible positive effect of rituximab which is worth investigating in future randomised controlled clinical trials.Trial registration numberNCT05877040.
Efficacy, safety and tolerability of rozanolixizumab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a randomised, subject-blind, investigator-blind, placebo-controlled, phase 2a trial and open-label extension study
Authors: Querol Luis , De Sèze Jérôme , Dysgaard Tina , Levine Todd , Rao T Hemanth , Rivner Michael , Hartung Hans-Peter , Kiessling Peter , Shimizu Saori , Marmol Dominika , Bozorg Ali , Colson Anny-Odile , Massow Ute , Eftimov Filip 
Published: May 2024

BackgroundChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a peripheral nerve disorder characterised by weakness and sensory loss. We assessed the neonatal Fc receptor inhibitor rozanolixizumab for CIDP management.MethodsCIDP01 (NCT03861481) was a randomised, subject-blind, investigator-blind, placebo-controlled, phase 2a study. Adults with definite or probable CIDP receiving subcutaneous or intravenous immunoglobulin maintenance therapy were randomised 1:1 to 12 once-weekly subcutaneous infusions of rozanolixizumab 10 mg/kg or placebo, stratified according to previous immunoglobulin administration route. Investigators administering treatment and assessing efficacy, and patients, were blinded. The primary outcome was a change from baseline (CFB) to day 85 in inflammatory Rasch-built Overall Disability Scale (iRODS) score. Eligible patients who completed CIDP01 entered the open-label extension CIDP04 (NCT04051944).ResultsIn CIDP01, between 26 March 2019 and 31 March 2021, 34 patients were randomised to rozanolixizumab or placebo (17 (50%) each). No significant difference in CFB to day 85 in iRODS centile score was observed between rozanolixizumab (least squares mean 2.0 (SE 3.2)) and placebo (3.4 (2.6); difference –1.5 (90% CI –7.5 to 4.5)). Overall, 14 (82%) patients receiving rozanolixizumab and 13 (76%) receiving placebo experienced a treatment-emergent adverse event during the treatment period. Across CIDP01 and CIDP04, rozanolixizumab was well tolerated over up to 614 days; no clinically meaningful efficacy results were seen. No deaths occurred.ConclusionsRozanolixizumab did not show efficacy in patients with CIDP in this study, although this could be due to a relatively high placebo stability rate. Rozanolixizumab was well tolerated over medium-to-long-term weekly use, with an acceptable safety profile.
Unveiling realistic mobility patterns with home–origin–destination data aggregation
Authors: Du Yunhan , Aoki Takaaki , Fujiwara Naoya 
Published: May 2024

AbstractThe availability of increasingly abundant mobility data in recent years has opened up new avenues for researchers to unravel human mobility patterns. Data aggregation methods have been introduced to gain a quantitative understanding of collective individual movements using these data. Nevertheless, the widely adopted origin–destination (OD) aggregation method for human mobility data lacks an essential piece of information: home location, which plays a vital role in characterizing individual movement patterns. In this study, we propose a novel data aggregation approach called home–origin–destination (HOD) with the aim of improving the accuracy of human mobility estimation. We compare the performance of various data aggregation methods for estimating population distribution. Our experimental results reveal more realistic mobility patterns when incorporating estimated home information, where individuals move out in the morning and return home before midnight. To further evaluate the effectiveness of the HOD approach, we conduct an entropy analysis to measure the unpredictability of human mobility. The HOD results exhibit lower entropy values than those in the other two cases, OD and home–destination (HD). These findings underscore the importance of incorporating home information in understanding and modeling human mobility. By leveraging the HOD data aggregation method, we can achieve more accurate population distribution estimates and capture the inherent dynamics of human movement
Characterization of a novel proton-CT scanner based on Silicon and LaBr$$_3$$(Ce) detectors
Authors: Nácher E. , Briz J. A. , Nerio A. N. , Perea A. , Távora V. G. , Tengblad O. , Ciemala M. , Cieplicka-Orynczak N. , Maj A. , Mazurek K. , Olko P. , Zieblinski M. , Borge M. J. G. 
Published: May 2024

AbstractTreatment planning systems at proton-therapy centres entirely use X-ray computed tomography (CT) as primary imaging technique to infer the proton treatment doses to tumour and healthy tissues. However, proton stopping powers in the body, as derived from X-ray images, suffer from important proton-range uncertainties. In order to reduce this uncertainty in range, one could use proton-CT images instead. The main goal of this work is to test the capabilities of a newly-developed proton-CT scanner, based on the use of a set of tracking detectors and a high energy resolution scintillator for the residual energy of the protons. Different custom-made phantoms were positioned at the field of view of the scanner and were irradiated with protons at the CCB proton-therapy center in Krakow. We measured with the phantoms at different angles and produced sinograms that were used to obtain reconstructed images by Filtered Back-Projection. The obtained images were used to determine the capabilities of our scanner in terms of spatial resolution and proton Relative Stopping Power (RSP) mapping and validate its use as proton-CT scanner. The results show that the scanner can produce medium-high quality images, with spatial resolution better than 2 mm in radiography, below 3 mm in tomography and resolving power in the RSP comparable to other state-of-the-art pCT scanners.
The automorphism group of finite 2-groups associated to the Macdonald group
Authors: Ocampo Alexander Montoya , Szechtman Fernando 
Published: May 2024

We consider the Macdonald group [Formula: see text] and its Sylow 2-subgroup [Formula: see text], where [Formula: see text] and [Formula: see text] is odd. Then J has order [Formula: see text], and nilpotency class 5 if [Formula: see text] and 3 if [Formula: see text]. We determine the automorphism group of the 2-groups J, [Formula: see text] and [Formula: see text], where [Formula: see text] and [Formula: see text]. Explicit multiplication, power, and commutator formulas for J, H and K are given, and used in the calculation of [Formula: see text], [Formula: see text] and [Formula: see text].
Antimicrobial and Wound Healing Performance of Polycaprolactone Electrospun-Based Nanofibers Incorporating Propolis and Quercus Infectoria Gall Extracts
Authors: Aliee Faezeh , Fahimirad Shohreh , Ganji Ali , Abtahi Hamid 
Published: May 2024

Background: A highly effective antibacterial wound dressing was developed in this investigation by developing a novel bioactive functional nanostructure. Methods: Ethanolic extracts of propolis (EEP) and Q.infectoria galls (QIG) were processed to obtain their respective extracts. The antibacterial properties of the individual EEP and QIG extracts and their combined effects were investigated. Based on the antibacterial test results, solutions containing polycaprolactone (PCL), PCL/EEP, PCL/QIG and PCL/EEP/QIG were prepared. These solutions were then used to fabricate nanobased mats through electrospinning. The resulting nanofibers were examined in terms of their physical, chemical and biological traits. In order to assess the wound healing capabilities, in vivo experiments were conducted, wherein the efficacy of the scaffolds in combating Staphylococcus aureus (MRSA) infections on wounds was evaluated. Results: The nanoscale structure of the electrospun nanofibers was confirmed through FESEM analysis, while the successful integration of EEP and QIG in the PCL-based electrospun nanofiber was validated using FTIR. By including both EEP and QIG bioactive extracts in the nanofiber, improved antibacterial and antioxidant activities were achieved without compromising the viability of human fibroblast cells. The use of PCL/EEP/QIG dressings led to wound closure rates of 85% and 100% on the 5th and 15th day of treatment, respectively, demonstrating the effectiveness of the combination of EEP and QIG extracts. Conclusions: The remarkable outcomes have presented encouraging prospects for using PCL/EEP/QIG as a highly effective wound dressing with antibacterial properties in clinical trials.
Chronic Volar Dislocation of the Distal Radioulnar Joint Stabilised by a Partial Extensor Carpi Ulnaris Tendon Strip – A Case Report
Authors: SANKARAN Ajeesh , KABIR Hannan Sheik , THUSHARA K. R. , SHAREEF Abdu P. P. 
Published: May 2024

Volar dislocation of the distal radioulnar joint is a rare injury that is often missed at initial presentation. We report a 21-year-old male patient who presented 2 months after sustaining this injury. He was successfully managed by open reduction and reconstruction of the dorsal radioulnar ligament using a partial distally based extensor carpi ulnaris tendon strip. A literature review showed only a few reported cases with varied methods for management. The technique utilised is analysed in comparison to the others. Level of Evidence: Level V (Therapeutic)
Ten‐Year Outcome of Recanalization or Medical Therapy for Concomitant Chronic Total Occlusion After Myocardial Infarction
Authors: van Veelen Anna , Coerkamp Casper F. , Somsen Yvemarie B.O. , Råmunddal Truls , Ioanes Dan , Laanmets Peep , van der Schaaf René J. , Eriksen Erlend , Bax Matthijs , Suttorp Maarten Jan , Strauss Bradley H. , Barbato Emanuele , Marques Koen M. , Meuwissen Martijn , Bertrand Olivier , van der Ent Martin , Knaapen Paul , Tijssen Jan G.P. , Claessen Bimmer E.P.M. , Hoebers Loes P.C. , Elias Joëlle , Henriques José P.S. , Henriques J.P.S. , Piek J.J. , de Winter R.J. , Koch K.T. , Vis M.M. , Baan J. , Wykrzykowska J. , Marques K.M. , Meuwissen M. , Koolen J. , Bax M. , Schotborgh C.E. , van der Ent M. , van der Schaaf R.J. , Slagboom T. , Amoroso G. , Suttorp M.J. , Råmunddal T. , Ioanes D. , Laanmets P. , Eriksen E. , Tuseth V. , Strauss B.H. , Bertrand O. , Barbato E. 
Published: May 2024

Background
The EXPLORE (Evaluating Xience and Left Ventricular Function in PCI on Occlusions After STEMI) trial was the first and only randomized trial investigating chronic total occlusion (CTO) percutaneous coronary intervention (PCI) early after primary PCI for ST‐segment–elevation myocardial infarction, compared with medical therapy for the CTO. We performed a 10‐year follow‐up of EXPLORE to investigate long‐term safety and clinical impact of CTO PCI after ST‐segment–elevation myocardial infarction, compared with no‐CTO PCI.

Methods and Results

In EXPLORE, 302 patients post‐ST‐segment–elevation myocardial infarction with concurrent CTO were randomized to CTO PCI within ≈1 week or no‐CTO PCI. We performed an extended clinical follow‐up for the primary end point of major adverse cardiac events, consisting of cardiovascular death, coronary artery bypass grafting, or myocardial infarction. Secondary end points included all‐cause death, angina, and dyspnea. Median follow‐up was 10 years (interquartile range, 8–11 years). The primary end point occurred in 25% of patients with CTO PCI and in 24% of patients with no‐CTO PCI (hazard ratio [HR], 1.11 [95% CI, 0.70–1.76]). Cardiovascular mortality was higher in the CTO PCI group (HR, 2.09 [95% CI, 1.10–2.50]), but all‐cause death was similar (HR, 1.53 [95% CI, 0.93–2.50]). Dyspnea relief was more frequent after CTO PCI (83% versus 65%,
P
=0.005), with no significant difference in angina.

Conclusions
This 10‐year follow‐up of patients post‐ST‐segment–elevation myocardial infarction randomized to CTO PCI or no‐CTO PCI demonstrated no clinical benefit of CTO PCI in major adverse cardiac events or overall mortality. However, CTO PCI was associated with a higher cardiovascular mortality compared with no‐CTO PCI. Our long‐term data support a careful weighing of effective symptom relief against an elevated cardiovascular mortality risk in CTO PCI decisions.

Registration

URL:
https://www.trialregister.nl
; Unique identifier: NTR1108.
Agreement of Fractional Flow Reserve Estimated by Computed Tomography With Invasively Measured Fractional Flow Reserve: A Systematic Review and Meta‐Analysis
Authors: Faulder Thomas I. , Prematunga Kurundeniya , Moloi Soniah B. , Faulder Lauren E. , Jones Rhondda , Moxon Joseph V. 
Published: May 2024

Background
Fractional flow reserve (FFR) is the ratio of blood pressure measured distal to a stenosis and pressure proximal to a stenosis. FFR can be estimated noninvasively using computed tomography (CT) although the usefulness of this technique remains controversial. This meta‐analysis evaluated the agreement of FFR estimated by CT (FFR‐CT) with invasively measured FFR. The study also evaluated the diagnostic accuracy of FFR‐CT, defined as the ability of FFR‐CT to classify lesions as hemodynamically significant (invasive FFR ≤0.8) or insignificant (invasive FFR >0.8).

Methods and Results
Forty‐three studies reporting on 7291 blood vessels from 5236 patients were included. A moderate positive linear relationship between FFR‐CT and invasively measured FFR was observed (Spearman correlation coefficient: 0.67). Agreement between the 2 measures increased as invasively measured FFR values approached 1. The overall diagnostic accuracy, sensitivity and specificity of FFR‐CT were 82.2%, 80.9%, and 83.1%, respectively. Diagnostic accuracy of 90% could be demonstrated for FFR‐CT values >0.90 and <0.49. The diagnostic accuracy of off‐site tools was 79.4% and the diagnostic accuracy of on‐site tools was 84.1%.

Conclusions
The agreement between FFR‐CT and invasive FFR is moderate although agreement is highest in vessels with FFR‐CT >0.9. Diagnostic accuracy varies widely with FFR‐CT value but is above 90% for FFR‐CT values >0.90 and <0.49. Furthermore, on‐site and off‐site tools have similar performance. Ultimately, FFR‐CT may be a useful adjunct to CT coronary angiography as a gatekeeper for invasive coronary angiogram.
An Overlooked Quotation from Phaedrus’ Appendix Perottina
Authors: Zago Giovanni 
Published: May 2024

Abstract
This paper analyses an overlooked quotation from Phaedrus’ Appendix Perottina in a grammatical miscellany by Godescalc of Orbais and makes a contribution to the textual history of Phaedrus’ fables; it also demonstrates once and for all, through irrefutable evidence, that the Appendix Perottina cannot be a humanistic forgery.
Persistent Severe Headache After Removal of Fungus Ball From the Sphenoid Sinus: A Case Report
Authors: Kim Tae Hoon , Kim SungHee 
Published: May 2024

Objective: Granulomatous invasive fungal sinusitis (GIFS) is a rare and life-threatening disease, whereas fungus ball (FB) is the most common form of noninvasive fungal sinusitis. Both GIFS and FB primarily develop in immunocompetent patients, with the former associated with higher mortality and morbidity. Methods: A chart review and review of the literature. Results: We present the case of a 77-year-old woman with mixed fungal sinusitis who was successfully treated with voriconazole. Conclusions: GIFS and FB can coexist in extremely rare cases, known as mixed fungal sinusitis; however, the diagnosis and subsequent treatment of mixed fungal sinusitis can be delayed because of a lack of awareness of the underlying concept. Therefore, it is crucial for clinicians to recognize the concept of mixed fungal sinusitis.