bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fcγ receptor binding is required for maximal immunostimulation by CD70-Fc
Authors: Dadas Osman , Allen Joel D. , Buchan Sarah L. , Kim Jinny , Chan H. T. Claude , Mockridge C. Ian , Duriez Patrick J. , Rogel Anne , Crispin Max , Al-Shamkhani Aymen 
Published: October 2023

IntroductionT cell expressed CD27 provides costimulation upon binding to inducible membrane expressed trimeric CD70 and is required for protective CD8 T cell responses. CD27 agonists could therefore be used to bolster cellular vaccines and anti-tumour immune responses. To date, clinical development of CD27 agonists has focussed on anti-CD27 antibodies with little attention given to alternative approaches.MethodsHere, we describe the generation and activity of soluble variants of CD70 that form either trimeric (t) or dimer-of-trimer proteins and conduct side-by-side comparisons with an agonist anti-CD27 antibody. To generate a dimer-of-trimer protein (dt), we fused three extracellular domains of CD70 to the Fc domain of mouse IgG1 in a ‘string of beads’ configuration (dtCD70-Fc).ResultsWhereas tCD70 failed to costimulate CD8 T cells, both dtCD70-Fc and an agonist anti-CD27 antibody were capable of enhancing T cell proliferation in vitro. Initial studies demonstrated that dtCD70-Fc was less efficacious than anti-CD27 in boosting a CD8 T cell vaccine response in vivo, concomitant with rapid clearance of dtCD70-Fc from the circulation. The accelerated plasma clearance of dtCD70-Fc was not due to the lack of neonatal Fc receptor binding but was dependent on the large population of oligomannose type glycosylation. Enzymatic treatment to reduce the oligomannose-type glycans in dtCD70-Fc improved its half-life and significantly enhanced its T cell stimulatory activity in vivo surpassing that of anti-CD27 antibody. We also show that whereas the ability of the anti-CD27 to boost a vaccine response was abolished in Fc gamma receptor (FcγR)-deficient mice, dtCD70-Fc remained active. By comparing the activity of dtCD70-Fc with a variant (dtCD70-Fc(D265A)) that lacks binding to FcγRs, we unexpectedly found that FcγR binding to dtCD70-Fc was required for maximal boosting of a CD8 T cell response in vivo. Interestingly, both dtCD70-Fc and dtCD70-Fc(D265A) were effective in prolonging the survival of mice harbouring BCL1 B cell lymphoma, demonstrating that a substantial part of the stimulatory activity of dtCD70-Fc in this setting is retained in the absence of FcγR interaction.DiscussionThese data reveal that TNFRSF ligands can be generated with a tunable activity profile and suggest that this class of immune agonists could have broad applications in immunotherapy.
Drifter observations of surface currents in the Cyprus Gyre
Authors: Poulain P.-M. , Menna M. , Mauri E. , Pirro A. , Hayes D. R. , Gildor H. 
Published: October 2023

Wavelet ridge analysis was applied to the data of drifters caught in the Cyprus Gyre in the eastern Mediterranean Sea to study surface currents at low (rotating circulation) and high (near-inertial motion) frequencies. Drifter observations indicate that the orbital speed is highest at about 30 km from the gyre center (reaching ~45 cm/s) and that the Rossby number in the gyre can be as high as 0.25. Drifters also show that strong near-inertial currents with speed of 35-40 cm/s can exceed the gyre rotation speed and that the background vorticity inside the gyre generally shifts the effective inertial frequency to values smaller than the local inertial frequency. As a result, the near-inertial currents are subinertial and are trapped in the mesoscale vortex. For example, the near-inertial motions in the Cyprus Gyre in June 2017 reached 40 cm/s in its inner core with a red shift of ~0.1 cpd, while on its edge they were limited to 10-20 cm/s, under similar wind forcing. This difference is due to trapping of the near-inertial energy inside the gyre. The observed inertial currents are largely driven by the local wind, especially when the effective inertial frequency becomes diurnal and resonance with wind diurnal variability occurs. A damped slab model of the inertial currents in the mixed layer is only partially successful in simulating the observations.
Comparison of glial fibrillary acidic protein-immunoglobulin G-associated myelitis with myelin oligodendrocyte glycoprotein-immunoglobulin G-associated myelitis
Authors: Sun Mengyang , Liu Hao , Zhu Bingqing , Liu Yang , Li Aijia , Wang Limei 
Published: October 2023

ObjectiveGlial fibrillary acidic protein-immunoglobulin G (GFAP-IgG)-associated myelitis and myelin oligodendrocyte glycoprotein-IgG (MOG-IgG)-associated myelitis have rarely been compared. Therefore, this study aimed to explore the clinical, laboratory, and imaging features of them to identify the differences.MethodsOverall, 14 and 24 patients with GFAP-IgG-and MOG-IgG-associated myelitis, respectively, were retrospectively screened and included in the study.ResultsAmong the 14 patients with GFAP-IgG-associated myelitis, the condition was more common in males (71.4%), with a median age of onset of 36.5 years, and more common in adults than in children (35.7%). In contrast, among the 24 patients with MOG-IgG-associated myelitis, the condition was equally divided between males and females, with a median age of onset of 9.5 years and more in children (66.7%) than in adults. The median age of onset of GFAP-IgG-associated myelitis was later than that of the MOG-IgG group. Isolated myelitis was rare in both groups. Elevated cerebrospinal fluid (CSF) protein levels were more prevalent in patients with GFAP-IgG-associated myelitis (64.3%) than in those with MOG-IgG-associated myelitis (16.7%) (p &lt; 0.05), whereas patchy gadolinium enhancement of the cerebral lesion site was less common in patients with GFAP-IgG-associated myelitis than in those with MOG-IgG associated myelitis (p &lt; 0.05). Six patients had a combination of other neurological autoantibodies, the specific mechanism of the overlapping antibodies remains unclear.ConclusionCerebrospinal fluid analysis and gadolinium enhanced MRI examination may help to distinguish the two kinds of myelitis.
Thyroid nodule malignancy is associated with increased non-invasive hepatic fibrosis scores in metabolic subjects
Authors: Crudele Lucilla , Novielli Fabio , De Matteis Carlo , Petruzzelli Stefano , Suppressa Patrizia , Berardi Elsa , Antonica Gianfranco , Piazzolla Giuseppina , Sabbà Carlo , Graziano Giusi , Moschetta Antonio 
Published: October 2023

IntroductionThyroid cancer incidence is increasing, and adiposity-related conditions are gaining space in its pathogenesis. In this study, we aimed to detect any anthropometric, biohumoral, and clinical features that might be associated with thyroid nodule malignancy, potentially representing novel non-invasive markers of thyroid cancer.Materials and methodsThe study was conducted in a group of 142 consecutive outpatients (47 men and 95 women) who underwent fine-needle aspiration biopsy/cytology (FNAB/C) due to suspicion of malignancy from January 2018 to September 2022. We compared lipid and glycemic blood profiles as well as non-invasive liver fibrosis indexes such as aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), AST to platelet ratio index (APRI), and fibrosis index based on four factors (FIB-4) between patients with benign and malignant newly diagnosed nodules. Then, we performed receiver operating characteristic (ROC) analysis to assess their best cutoff values for discrimination of malignant nodules and chi-squared test to evaluate the association of specific dysmetabolic conditions with malignancy. To understand whether and to what degree dysmetabolic conditions increased the risk of thyroid nodule malignancy, we also calculated the odds ratio (OR) of the main biomarkers.ResultsAfter FNAB/C, 121 (85%) patients were diagnosed with benign thyroid nodules, while 21 (15%) individuals were diagnosed with thyroid cancer. Comparing patients with benign and malignant nodules, we found that individuals with thyroid cancer exhibited increased body mass index (BMI) (p = 0.048) and fasting plasma glucose (p = 0.046). Intriguingly, considering non-invasive scores for liver fibrosis, subjects with thyroid cancer presented increased AAR (p &lt; 0.001) and APRI (p = 0.007), and these scores were associated with malignancy (p &lt; 0.005) with OR = 7.1 and OR = 5, respectively. Moreover, we showed that only in the cancer group, low levels of vitamin D correlated with stigmata of impaired metabolism.DiscussionIn our study, AAR and APRI scores were associated with thyroid nodule malignancy and could be used to predict it and to speed up the diagnostic process. From a pathogenic point of view, we speculated that metabolic-associated fatty liver disease (MAFLD) along with hyperglycemia and vitamin D deficiency may represent putative drivers of thyroid carcinogenesis.
PD-1 blockade combined with gemcitabine plus nab-paclitaxel is superior to chemotherapy alone in the management of unresectable stage III/IV pancreatic cancer: a retrospective real-world study
Authors: Cheng Daoan , Hu Jing , Wu Xiaoyu , Wang Banglu , Chen Rui , Zhao Weiqing , Fang Cheng , Ji Mei 
Published: October 2023

BackgroundPancreatic cancer (PC) is widely recognized as one of the most malignant forms of cancer worldwide. Monotherapy with immune checkpoint inhibitors (ICI) has shown limited efficacy in treating this disease. There was controversy surrounding whether combining ICI with chemotherapy provided superior outcomes compared to chemotherapy alone.MethodsIn this study, patients diagnosed with unresectable stage III/IV pancreatic cancer (PC) were classified as receiving programmed cell death protein 1 (PD-1) blockade plus gemcitabine and nab-paclitaxel (AG regimen) (PD-1/chemo, n=27, 50.9%) or chemotherapy alone (chemo, n=26, 49.1%) arm. The primary study endpoints included progression-free survival (PFS) and overall survival (OS), with an additional assessment of treatment-related adverse events graded as three or higher. Chi-square (χ2) statistics were employed to analyze the clinical differences between the two groups, while Kaplan-Meier curves were used to assess the difference in PFS and OS. Statistical significance was defined as P-values less than 0.05 (P &lt; 0.05).ResultsThe median follow-up duration was 22 months (range 1-28 months). In the PD-1/chemo arm, the median PFS was eight months, whereas it was 3.5 months in the chemo arm (HR=0.459, 95% CI: 0.252-0.846, P=0.002). Furthermore, the median OS was 15 months in the PD-1/chemo arm and eight months in the chemo arm (HR=0.345, 95% CI: 0.183-0.653, P&lt;0.001). Within the PD-1/chemo arm, 15 (55.6%) patients experienced grade 3 treatment-related adverse events, compared to 13 (50.0%) patients in the chemo arm.ConclusionsPD-1 blockade combined with nab-paclitaxel plus gemcitabine demonstrated superior efficacy to chemotherapy alone for unresectable stage III/IV PC patients. Future studies were warranted to identify immunosensitive patient subgroups within the PC population, ultimately leading to the development of more efficacious therapeutic strategies.
A systematic review of data sources for artificial intelligence applications in pediatric brain tumors in Europe: implications for bias and generalizability
Authors: Tozzi Alberto Eugenio , Croci Ileana , Voicu Paul , Dotta Francesco , Colafati Giovanna Stefania , Carai Andrea , Fabozzi Francesco , Lacanna Giuseppe , Premuselli Roberto , Mastronuzzi Angela 
Published: October 2023

IntroductionEurope works to improve cancer management through the use of artificialintelligence (AI), and there is a need to accelerate the development of AI applications for childhood cancer. However, the current strategies used for algorithm development in childhood cancer may have bias and limited generalizability. This study reviewed existing publications on AI tools for pediatric brain tumors, Europe's most common type of childhood solid tumor, to examine the data sources for developing AI tools.MethodsWe performed a bibliometric analysis of the publications on AI tools for pediatric brain tumors, and we examined the type of data used, data sources, and geographic location of cohorts to evaluate the generalizability of the algorithms.ResultsWe screened 10503 publications, and we selected 45. A total of 34/45 publications developing AI tools focused on glial tumors, while 35/45 used MRI as a source of information to predict the classification and prognosis. The median number of patients for algorithm development was 89 for single-center studies and 120 for multicenter studies. A total of 17/45 publications used pediatric datasets from the UK.DiscussionSince the development of AI tools for pediatric brain tumors is still in its infancy, there is a need to support data exchange and collaboration between centers to increase the number of patients used for algorithm training and improve their generalizability. To this end, there is a need for increased data exchange and collaboration between centers and to explore the applicability of decentralized privacy-preserving technologies consistent with the General Data Protection Regulation (GDPR). This is particularly important in light of using the European Health Data Space and international collaborations.
Assessment of Hazardous Gaming in children and its dissimilarities and overlaps with Internet Gaming Disorder
Authors: Kewitz Sonja , Leo Katharina , Rehbein Florian , Lindenberg Katajun 
Published: October 2023

Background and aimsChildren have been vastly overlooked in Internet Gaming Disorder (IGD) and Hazardous Gaming research so far. The diagnoses are listed in different ICD-11 chapters (addiction vs. problematic health condition) and are thus considered as distinct constructs. However, screening tools for children do not exist yet. We aimed to investigate the psychometric properties of an existing IGD screening tool modified to also assess Hazardous Gaming in children. Further, we aimed to compare the dissimilarity and overlap between (subclinical) IGD and Hazardous Gaming in children.MethodsThe study analyzed data from a mixed school and clinical sample. Data from N = 871 children aged between 8 and 12 years of age (M = 10.3, SD = 0.90) were analyzed. Data were collected via the Video Game Dependency Scale (CSAS) in its parent report version, which was adapted to assess Hazardous Gaming symptoms in addition to the IGD symptoms. Item analyses and reliability and factor analyses were conducted on the Hazardous Gaming version.ResultsThe results show that the adapted CSAS version that assesses Hazardous Gaming symptoms in children mostly shows acceptable psychometric properties. Explorative Factor Analysis (EFA) shows a two-factor structure with one factor of higher order. Additionally, results show that 35.2% of all children meeting the threshold for Hazardous Gaming exclusively meet criteria for Hazardous Gaming but not for (subclinical) IGD. Vice versa, 91.3% of children with IGD also meet the criteria for Hazardous Gaming.DiscussionHazardous Gaming and (subclinical) IGD are distinct constructs with some overlaps and might have a temporal relation. We recommend adding four items to assess Hazardous Gaming using the CSAS and further evaluate the validity. The assessment of Hazardous Gaming in children is crucial because it might occur earlier than subclinical or full-syndrome IGD.
Health staff perceptions of patient safety and associated factors in hospitals in Vietnam
Authors: Thu Nguyen Thi Hoai , Anh Bui Thi My , Ha Nguyen Thi Thu , Tien Doan Ngoc Thuy , Giang Pham Huong , Nga Tran Thi , Nam Nguyen Hoang , Hung Phung Thanh 
Published: October 2023

IntroductionPatient safety is a global challenge of preventing and mitigating medical errors which might harm patients during their course of treatment and care. This study was employed to contribute to the existing literature aimed to assess patient safety culture among health staff and to determine predictors of health staff perceptions of patient safety in hospitals in Vietnam.MethodsA cross-sectional study was conducted in three hospitals of Vietnam with a total of 763 participants. This study used the Hospital Patient Safety Scale developed by the American Health and Quality Research Organization.ResultsIn general, 8 of 12 patient safety dimensions in two hospital; and 10 of 12 dimensions in a third hospital had average scores of 60% and above positive responses. The communication openness and organizational learning dimensions were found to be significant different when comparing hospitals. Regarding sample characteristics, department (subclinical department) and health staff positions (nurses/technicians, pharmacists) were significant predictors in the total model including three hospitals (R2 = 0.07).ConclusionThis study reported that communication openness and organization learning are two aspects that need to be improved they are strongly related to patient safety culture and to knowledge exchange among health staff. It has been suggested that hospitals should deliver patient safety training courses and establish a supportive learning environment to improve these challenges.
Uptake of and intention to use oral pre-exposure prophylaxis for HIV among pregnant and post-natal women in Eswatini: a cross-sectional survey
Authors: Khumalo Philisiwe Ntombenhle , Mkhonta Siphiwesihle Sibonisiwe , Kindandi Kikanda , Matse Sindy , Dlamini Phinda Brian , Tukei Vincent , Machekano Rhoderick , Woelk Godfrey 
Published: October 2023

IntroductionIn Eswatini, HIV incidence among women of childbearing age is 1.45%. Eswatini introduced oral pre-exposure prophylaxis (PrEP) for HIV prevention in 2016 and requires that all HIV-negative pregnant and post-natal women (PPW) visiting health care facilities be offered PrEP.MethodsBetween September-November 2021, we conducted a survey among HIV-negative PPW from 16 purposively selected healthcare facilities in the Hhohho and Shiselweni regions in Eswatini. We interviewed consenting HIV-negative PPW using a structured questionnaire to collect data on PrEP knowledge, attitudes, intentions, and practices, as well as information on partner HIV status and stigma. Multivariate logistic regression was used to determine predictors of PrEP use and intention, adjusted for significant covariates.ResultsOf 1,484 PPW women approached, 1,149 consented and were interviewed, of whom 704 (61.3%) were post-partum and 445 (38.7%) pregnant. The median age was 25 years [Interquartile Range (IQR) = 21–30 years], with 533 (46.4%) 18–24 years old. Among the 1,149 women, 930 (80.7%) had ever heard about PrEP; 635 (55.3%) had knowledge about PrEP; 183 (15.9%) were currently using PrEP; and 285 (24.8%) had ever used PrEP. Increased odds of PrEP use were associated having HIV-positive male partner (aOR:7.76, 95%CI 3.53- 17.04); positive attitudes to PrEP (aOR:1.56, 95%CI: 1.02–2.40); and high self-efficacy (aOR:1.49, 95%CI:1.13–1.98). Among 864 women who never used PrEP, 569 (65.3%) intended to use PrEP in the future. Odds of intention to use PrEP were higher among women with low levels of education (aOR:2.23, 95% CI: 1.32–3.77); who ever heard about PrEP (aOR:1.69, 95%CI: 1.12–2.56); and had high self-efficacy (aOR:1.57, 95%CI: 1.31–1.87). Regarding stigma, among all women, 759 (66%) either agreed or strongly agreed that people would think they have HIV if they were to use PrEP; 658 (57.3%) reported they would be labelled as having multiple sex partners; 468 (40.7%) reported that their partner would think they are having risky sex with other people. Of 102 women who had discontinued PrEP, a majority stopped due to side effects 32 (35.2%).ConclusionOnly about 50% of women had knowledge of PrEP, and PrEP uptake among PPW was low, though intention to use appeared high. More efforts to reduce stigma and promote PrEP use, including adequate information on side effects, are needed.
Simulation of an Elastic Rod Whirling Instabilities by Using the Lattice Boltzmann Method Combined with an Immersed Boundary Method
Authors: Alapati Suresh , Che Wooseong , Rao Sunkara Srinivasa , Phan Giang T. T. 
Published: October 2023

Mathematical modeling and analysis of biologically inspired systems has been a fascinating research topic in recent years. In this work, we present the results obtained from the simulation of an elastic rod (that mimics a flagellum axoneme) rotational motion in a viscous fluid by using the lattice Boltzmann method (LBM) combined with an immersed boundary method (IBM). A finite element model consists of a set of beam and truss elements used to discretize the flagellum axoneme while the fluid flow is solved by the well-known LBM. The hydrodynamic coupling to maintain the no-slip boundary condition between the fluid and the elastic rod is conducted with the IBM. The rod is actuated with a torque applied at its base cross-section that acts as a driving motor of the axoneme. We simulated the rotational dynamics of the rod for three different rotational frequencies (low, medium, and high) of the motor. To compare with previous publication results, we chose the sperm number Sp=L(4πμω)/(EI)1/4 as the validation parameter. We found that at the low rotational frequency, f = 1.5 Hz, the rod performs stable twirling motion after attaining an equilibrium state (the rod undergoes rigid rotation about its axis). At the medium frequency, f = 2.65 Hz, the rod undergoes whirling motion, where the tip of the rod rotates about the central rotational axis of the driving motor. When the frequency increases further, i.e., when it reaches the critical value, fc ≈ 2.7 Hz, the whirling motion becomes over-whirling, where the tip of the filament falls back to the base and performs a steady crank-shafting motion. All three rotational dynamics, twirling, whirling, and over-whirling, and the critical value of rotational frequency are in good agreement with the previously published results. We also observed that our present simulation technique is computationally more efficient than previous works.
PSRGAN: Perception-Design-Oriented Image Super Resolution Generative Adversarial Network
Authors: Wu Tao , Xiong Shuo , Liu Hui , Zhao Yangyang , Tuo Haoran , Li Yi , Zhang Jiaxin , Liu Huaizheng 
Published: October 2023

Among recent state-of-the-art realistic image super-resolution (SR) intelligent algorithms, generative adversarial networks (GANs) have achieved impressive visual performance. However, there has been the problem of unsatisfactory perception of super-scored pictures with unpleasant artifacts. To address this issue and further improve visual quality, we proposed a perception-design-oriented PSRGAN with double perception turbos for real-world SR. The first-perception turbo in the generator network has a three-level perception structure with different convolution kernel sizes, which can extract multi-scale features from four 14 size sub-images sliced by original LR image. The slice operation expands adversarial samples to four and could alleviate artifacts during GAN training. The extracted features will be eventually concatenated in later 3 × 2 upsampling processes through pixel shuffle to restore SR image with diversified delicate textures. The second-perception turbo in discriminators has cascaded perception turbo blocks (PTBs), which could further perceive multi-scale features at various spatial relationships and promote the generator to restore subtle textures driven by GAN. Compared with recent SR methods (BSRGAN, real-ESRGAN, PDM_SR, SwinIR, LDL, etc.), we conducted an extensive test with a ×4 upscaling factor on various datasets (OST300, 2020track1, RealSR-Canon, RealSR-Nikon, etc.). We conducted a series of experiments that show that our proposed PSRGAN based on generative adversarial networks outperforms current state-of-the-art intelligent algorithms on several evaluation metrics, including NIQE, NRQM and PI. In terms of visualization, PSRGAN generates finer and more natural textures while suppressing unpleasant artifacts and achieves significant improvements in perceptual quality.