bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bispecific killer cell engager with high affinity and specificity toward CD16a on NK cells for cancer immunotherapy
Authors: Nikkhoi Shahryar Khoshtinat , Li Geng , Eleya Suha , Yang Ge , Vandavasi Venu Gopal , Hatefi Arash 
Published: January 2023

IntroductionThe Fc region of monoclonal antibodies (mAbs) interacts with the CD16a receptor on natural killer (NK) cells with “low affinity” and “low selectivity”. This low affinity/selectivity interaction results in not only suboptimal anticancer activity but also induction of adverse effects. CD16a on NK cells binds to the antibody-coated cells, leading to antibody-dependent cell-mediated cytotoxicity (ADCC). Recent clinical data have shown that the increased binding affinity between mAb Fc region and CD16a receptor is responsible for significantly improved therapeutic outcomes. Therefore, the objective of this study was to develop a bispecific killer cell engager (BiKE) with high affinity and specificity/selectivity toward CD16a receptor for NK cell-based cancer immunotherapy.MethodsTo engineer BiKE, a llama was immunized, then high binding anti-CD16a and anti-HER2 VHH clones were isolated using phage display. ELISA, flow cytometry, and biolayer interferometry (BLI) data showed that the isolated anti-CD16a VHH has high affinity (sub-nanomolar) toward CD16a antigen without cross-reactivity with CD16b-NA1 on neutrophils or CD32b on B cells. Similarly, the data showed that the isolated anti-HER2 VHH has high affinity/specificity toward HER2 antigen. Using a semi-flexible linker, anti-HER2 VHH was recombinantly fused with anti-CD16a VHH to create BiKE:HER2/CD16a. Then, the ability of BiKE:HER2/CD16a to activate NK cells to release cytokines and kill HER2+ cancer cells was measured. As effector cells, both high-affinity haNK92 (CD16+, V176) and low-affinity laNK92 (CD16+, F176) cells were used.Results and discussionThe data showed that the engineered BiKE:HER2/CD16a activates haNK92 and laNK92 cells to release cytokines much greater than best-in-class mAbs in the clinic. The cytotoxicity data also showed that the developed BiKE induces higher ADCC to both ovarian and breast cancer cells in comparison to Trazimera™ (trastuzumab). According to the BLI data, BiKE:HER2/CD16 recognizes a different epitope on CD16a antigen than IgG-based mAbs; thus, it provides the opportunity for not only monotherapy but also combination therapy with other antibody drugs such as checkpoint inhibitors and antibody-drug conjugates. Taken together, the data demonstrate the creation of a novel BiKE with high affinity and specificity toward CD16a on NK cells with the potential to elicit a superior therapeutic response in patients with HER2+ cancer than existing anti-HER2 mAbs.
Predicting melanoma survival and metastasis with interpretable histopathological features and machine learning models
Authors: Couetil Justin , Liu Ziyu , Huang Kun , Zhang Jie , Alomari Ahmed K. 
Published: January 2023

IntroductionMelanoma is the fifth most common cancer in US, and the incidence is increasing 1.4% annually. The overall survival rate for early-stage disease is 99.4%. However, melanoma can recur years later (in the same region of the body or as distant metastasis), and results in a dramatically lower survival rate. Currently there is no reliable method to predict tumor recurrence and metastasis on early primary tumor histological images.MethodsTo identify rapid, accurate, and cost-effective predictors of metastasis and survival, in this work, we applied various interpretable machine learning approaches to analyze melanoma histopathological H&amp;E images. The result is a set of image features that can help clinicians identify high-risk-of-metastasis patients for increased clinical follow-up and precision treatment. We use simple models (i.e., logarithmic classification and KNN) and “human-interpretable” measures of cell morphology and tissue architecture (e.g., cell size, staining intensity, and cell density) to predict the melanoma survival on public and local Stage I–III cohorts as well as the metastasis risk on a local cohort.ResultsWe use penalized survival regression to limit features available to downstream classifiers and investigate the utility of convolutional neural networks in isolating tumor regions to focus morphology extraction on only the tumor region. This approach allows us to predict survival and metastasis with a maximum F1 score of 0.72 and 0.73, respectively, and to visualize several high-risk cell morphologies.DiscussionThis lays the foundation for future work, which will focus on using our interpretable pipeline to predict metastasis in Stage I &amp; II melanoma.
Normal tension glaucoma: A dynamic optical coherence tomography angiography study
Authors: Van Eijgen Jan , Heintz Alexander , van der Pluijm Claire , Delporte Margaux , De Witte Dries , Molenberghs Geert , Barbosa-Breda João , Stalmans Ingeborg 
Published: January 2023

PurposeVascular dysregulation seems to play a role in the pathogenesis of glaucoma, in particular normal tension glaucoma (NTG). The development of optical coherence tomography angiography (OCTA) enabled the measurement of the retinal microvasculature non-invasively and with high repeatability. Nonetheless, only a few studies transformed OCTA into a dynamic examination employing a sympathomimetic stimulus. The goal of this study was to use this dynamic OCTA exam (1) to differentiate healthy individuals from glaucoma patients and (2) to distinguish glaucoma subcategories, NTG and high-tension primary open angle glaucoma (POAG).MethodsRetinal vessel density (VD) in NTG patients (n = 16), POAG patients (n = 12), and healthy controls (n = 14) was compared before and during a hand grip test with a hydraulic dynamometer.ResultsAt baseline, mean peripapillary VD was lower in POAG and NTG (42.6 and 48.5%) compared to healthy controls (58.1%; p &lt; 0.001) and higher in NTG compared to POAG (p = 0.024) when corrected for mean arterial pressure (MAP). Peripapillary and macular (superficial and deep) VD differences were found for gender, age, and baseline MAP. No change in VD occurred (pre-/post-stimulus) in any of the groups.ConclusionRetinal VD loss in glaucoma patients was confirmed and the necessity to correct for gender, age and especially MAP was established. Although replication in a larger population is necessary, OCTA might not be the most suitable method to dynamically evaluate the retinal microvasculature.
A scoping review on the use and usefulness of online symptom checkers and triage systems: How to proceed?
Authors: Pairon Anthony , Philips Hilde , Verhoeven Veronique 
Published: January 2023

BackgroundPatients are increasingly turning to the Internet for health information. Numerous online symptom checkers and digital triage tools are currently available to the general public in an effort to meet this need, simultaneously acting as a demand management strategy to aid the overburdened health care system. The implementation of these services requires an evidence-based approach, warranting a review of the available literature on this rapidly evolving topic.ObjectiveThis scoping review aims to provide an overview of the current state of the art and identify research gaps through an analysis of the strengths and weaknesses of the presently available literature.MethodsA systematic search strategy was formed and applied to six databases: Cochrane library, NICE, DARE, NIHR, Pubmed, and Web of Science. Data extraction was performed by two researchers according to a pre-established data charting methodology allowing for a thematic analysis of the results.ResultsA total of 10,250 articles were identified, and 28 publications were found eligible for inclusion. Users of these tools are often younger, female, more highly educated and technologically literate, potentially impacting digital divide and health equity. Triage algorithms remain risk-averse, which causes challenges for their accuracy. Recent evolutions in algorithms have varying degrees of success. Results on impact are highly variable, with potential effects on demand, accessibility of care, health literacy and syndromic surveillance. Both patients and healthcare providers are generally positive about the technology and seem amenable to the advice given, but there are still improvements to be made toward a more patient-centered approach. The significant heterogeneity across studies and triage systems remains the primary challenge for the field, limiting transferability of findings.ConclusionCurrent evidence included in this review is characterized by significant variability in study design and outcomes, highlighting the significant challenges for future research.An evolution toward more homogeneous methodologies, studies tailored to the intended setting, regulation and standardization of evaluations, and a patient-centered approach could benefit the field.
Choroidal morphologic and vascular features in patients with unilateral idiopathic epiretinal membranes: An optical coherence tomography analysis integrated with assessment of retinal layers
Authors: Wang Xinglin , Yang Jiarui , Wang Changguan , Li Xuemin 
Published: January 2023

IntroductionIntegrated analysis of retinal and choroidal morphologic and vascular features is urgently needed to examine whether and how these two elements interact with each other, thus contributing to visual impairment in patients with idiopathic epiretinal membranes (iERMs).MethodsAn observational retrospective study consisting of 181 patients diagnosed with unilateral iERM between August 2019 and July 2022 was carried out at Peking University Third Hospital. All patients underwent a standardized set of ophthalmologic examinations, including EDI-OCT and OCTA scanning, and were subsequently categorized into four stages according to current classification schemes based on their OCT findings. Altogether, 15 qualitative and quantitative parameters of both the retina (full-layer, inner and outer layers) and choroid were identified.ResultsThe results revealed variations in the choroidal vascularity index (CVI) among different stages of iERMs (p &lt; 0.001) for the first time. Distributions of retinal parameters across four stages of iERMs were validated. Correlation analysis between choroidal and retinal parameters showed that the CVI was associated with both inner and outer retinal morphologic biomarkers. Functional damage to retinal integrity was determined to be a strong contributor to visual acuity reduction in iERMs.DiscussionThis study complemented our present understanding of posterior segment structural and vascular alterations in iERMs.
The Saccharina latissima microbiome: Effects of region, season, and physiology
Authors: Burgunter-Delamare Bertille , Rousvoal Sylvie , Legeay Erwan , Tanguy Gwenn , Fredriksen Stein , Boyen Catherine , Dittami Simon M. 
Published: January 2023

IntroductionSaccharina latissima is a canopy-forming species of brown algae and, as such, is considered an ecosystem engineer. Several populations of this alga are exploited worldwide, and a decrease in the abundance of S. latissima at its southern distributional range limits has been observed. Despite its economic and ecological interest, only a few data are available on the composition of microbiota associated with S. latissima and its role in algal physiologyn.MethodsWe studied the whole bacterial community composition associated with S. latissima samples from three locations (Brittany, Helgoland, and Skagerrak) by 16S metabarcoding analyses at different scales: algal blade part, regions, season (at one site), and algal physiologic state.Results and DiscussionWe have shown that the difference in bacterial composition is driven by factors of decreasing importance: (i) the algal tissues (apex/meristem), (ii) the geographical area, (iii) the seasons (at the Roscoff site), and (iv) the algal host’s condition (healthy vs. symptoms). Overall, Alphaproteobacteria, Gammaproteobacteria, and Bacteroidia dominated the general bacterial communities. Almost all individuals hosted bacteria of the genus Granulosicoccus, accounting for 12% of the total sequences, and eight additional core genera were identified. Our results also highlight a microbial signature characteristic for algae in poor health independent of the disease symptoms. Thus, our study provides a comprehensive overview of the S. latissima microbiome, forming a basis for understanding holobiont functioning.
Metabolome and microbiome analysis revealed the effect mechanism of different feeding modes on the meat quality of Black Tibetan sheep
Authors: Zhang Xue , Han Lijuan , Gui Linsheng , Raza Sayed Haidar Abbas , Hou Shengzhen , Yang Baochun , Wang Zhiyou , Ma Ying , Makhlof Raafat T. M. , Alhuwaymil Zamzam , Ibrahim Samah F. 
Published: January 2023

IntroductionBlack Tibetan sheep is one of the primitive sheep breeds in China that is famous for its great eating quality and nutrient value but with little attention to the relationship between feeding regimes and rumen metabolome along with its impact on the muscle metabolism and meat quality.MethodsThis study applies metabolomics-based analyses of muscles and 16S rDNA-based sequencing of rumen fluid to examine how feeding regimes influence the composition of rumen microbiota, muscle metabolism and ultimately the quality of meat from Black Tibetan sheep. Twenty-seven rams were randomly assigned to either indoor feeding conditions (SG, n = 9), pasture grazing with indoor feeding conditions (BG, n = 9) or pasture grazing conditions (CG, n = 9) for 120 days.ResultsThe results showed that, compared with BG and CG, SG improved the quality of Black Tibetan sheep mutton by preventing a decline in pH and increasing fat deposition to enhance the color, tenderness and water holding capacity (WHC) of the Longissimus lumborum (LL). Metabolomics and correlation analyses further indicated that the feeding regimes primarily altered amino acid, lipid and carbohydrate metabolism in muscles, thereby influencing the amino acid (AA) and fatty acid (FA) levels as well as the color, tenderness and WHC of the LL. Furthermore, SG increased the abundance of Christensenellaceae R-7 group, [Eubacterium] coprostanoligenes group, Methanobrevibacter, Ruminococcus 2 and Quinella, decreased the abundance of Lactobacillus, Prevotella 1 and Rikenellaceae RC9 gut group, and showed a tendency to decrease the abundance of Succinivibrio and Selenomonas 1. Interestingly, all of these microorganisms participated in the deposition of AAs and FAs and modified the levels of different metabolites involved in the regulation of meat quality (maltotriose, pyruvate, L-ascorbic acid, chenodeoxycholate, D-glucose 6-phosphate, glutathione, etc.).DiscussionOverall, the results suggest that feeding Black Tibetan sheep indoors with composite forage diet was beneficial to improve the mouthfeel of meat, its color and its nutritional value by altering the abundance of rumen bacteria which influenced muscle metabolism.
Progressive structural and covariance connectivity abnormalities in patients with Alzheimer’s disease
Authors: Xiao Yaqiong , Wang Jiaojian , Huang Kaiyu , Gao Lei , Yao Shun 
Published: January 2023

BackgroundAlzheimer’s disease (AD) is one of most prevalent neurodegenerative diseases worldwide and characterized by cognitive decline and brain structure atrophy. While studies have reported substantial grey matter atrophy related to progression of AD, it remains unclear about brain regions with progressive grey matter atrophy, covariance connectivity, and the associations with cognitive decline in AD patients.ObjectiveThis study aims to investigate the grey matter atrophy, structural covariance connectivity abnormalities, and the correlations between grey matter atrophy and cognitive decline during AD progression.MaterialsWe analyzed neuroimaging data of healthy controls (HC, n = 45) and AD patients (n = 40) at baseline (AD-T1) and one-year follow-up (AD-T2) obtained from the Alzheimer’s Disease Neuroimaging Initiative. We investigated AD-related progressive changes of grey matter volume, covariance connectivity, and the clinical relevance to further understand the pathological progression of AD.ResultsThe results showed clear patterns of grey matter atrophy in inferior frontal gyrus, prefrontal cortex, lateral temporal gyrus, posterior cingulate cortex, insula, hippocampus, caudate, and thalamus in AD patients. There was significant atrophy in bilateral superior temporal gyrus (STG) and left caudate in AD patients over a one-year period, and the grey matter volume decrease in right STG and left caudate was correlated with cognitive decline. Additionally, we found reduced structural covariance connectivity between right STG and left caudate in AD patients. Using AD-related grey matter atrophy as features, there was high discrimination accuracy of AD patients from HC, and AD patients at different time points.
Bilingualism and creativity across development: Evidence from divergent thinking and convergent thinking
Authors: Zheng Yifan , Denervaud Solange , Durrleman Stephanie 
Published: January 2023

IntroductionNumerous studies have demonstrated the benefits of creativity from bilingualism. Divergent thinking and convergent thinking are considered the two most important components of creativity. Various (although not all) studies have concluded that bilingual children outperform monolingual children in divergent thinking, however, no study on children or adolescents so far has explored the relation between bilingualism and convergent thinking, or the brain structural basis of interaction between bilingualism and creativity. This study aimed to explore the impact of bilingualism on both convergent and divergent thinking in children and adolescents based on neuropsychological assessments, and the possible structural basis of the effect of bilingualism on creativity by a whole-brain analysis of regional gray matter volume (rGMV) and cortical thickness in children and adolescents.Methods92 healthy children and adolescents of age 4–18 were recruited from public or private schools in the French-speaking side of Switzerland. Demographic data of the participants were collected, including gender, age, pedagogy, usage of language, and parents’ socioeconomic status. Most of the participants underwent the neuropsychological assessments of divergent thinking, convergent thinking, and fluid intelligence. Structural image data of 75 participants were analyzed. Both voxel-based morphometry (VBM) and surface-based morphometry (SBM) were processed, to perform the analyses of rGMV and cortical thickness respectively.ResultsThe outcomes indicated that convergent thinking, but not divergent thinking benefits from bilingualism in children and adolescents. However, this bilingual advantage appears to weaken across development. Unexpectedly, no significant correlation between morphometry and bilingualism was found. Neither divergent thinking scores nor convergent thinking scores showed any significant correlation with rGMV. However, the whole brain SBM showed that the cortical thickness in the right supplementary motor area (SMA) was negatively correlated with convergent thinking scores, which suggested that the children and adolescents with higher convergent thinking abilities may have thinner, more mature, and more activated cortex in the right SMA.DiscussionBilingualism and cortical thinness in the right SMA might facilitate convergent thinking independently, by enhancing this selective ability.
Loss of CAMK2G affects intrinsic and motor behavior but has minimal impact on cognitive behavior
Authors: Rigter Pomme M. F. , de Konink Charlotte , van Woerden Geeske M. 
Published: January 2023

IntroductionThe gamma subunit of calcium/calmodulin-dependent protein kinase 2 (CAMK2G) is expressed throughout the brain and is associated with neurodevelopmental disorders. Research on the role of CAMK2G is limited and attributes different functions to specific cell types.MethodsTo further expand on the role of CAMK2G in brain functioning, we performed extensive phenotypic characterization of a Camk2g knockout mouse.ResultsWe found different CAMK2G isoforms that show a distinct spatial expression pattern in the brain. Additionally, based on our behavioral characterization, we conclude that CAMK2G plays a minor role in hippocampus-dependent learning and synaptic plasticity. Rather, we show that CAMK2G is required for motor function and that the loss of CAMK2G results in impaired nest-building and marble burying behavior, which are innate behaviors that are associated with impaired neurodevelopment.DiscussionTaken together, our results provide evidence for a unique function of this specific CAMK2 isozyme in the brain and further support the role of CAMK2G in neurodevelopment.
Comparison of the accuracy of axial length measurement by different imaging methods in Sprague Dawley rats
Authors: Wu Yajun , Luo Xiangdong , Feng Yuliang , Yang Jiasong , Fan Hua , Cen Xiaobo , Li Wensheng 
Published: January 2023

BackgroundObtaining accurate axial length (AL) is very important for the establishment of animal models of myopia. The purpose of this study is to compare the accuracy of Quantel A-B scan, OD-1 A scan, and vernier caliper in measuring AL in Sprague Dawley (SD) rats.MethodsIn total, 60 5-week-old SD rats were divided into female rat group (n = 30) and male rat group (n = 30). Quantel A-B scan and OD-1 A scan were, respectively, used to measure the AL of both eyes of each living rat, and vernier caliper was used to measure the anterior-posterior diameter of each rat’s eyeball. Besides, the correlation between refractive error (RE) and AL measured by different instruments was evaluated, and the accuracy of the three measurement methods was compared according to gender and left/right eyes.ResultsThere were significant differences in AL and diopter of SD rats at the same age (p &lt; 0.05). the AL of male rats was greater than that of female rats, while diopter (D) was the opposite; There was no significant difference in AL and D between left and right eyes in the same SD rats (p &gt; 0.05); There were statistical differences among the three measurement methods (p &lt; 0.05), AL measured by vernier caliper was the largest, followed by Quantel A-B scan, OD-1 A scan; Difference in AL between male and female was not statistically significant between the results obtained by Quantel A-B scan and vernier caliper (p &gt; 0.05), but there were statistically significant differences between the other two measurement methods (p &lt; 0.05).ConclusionSex is the influencing factor of AL and RE. Imaging measurement can accurately measure the AL in living small rodents. Compared with OD-1 A scan, Quantel A-B scan may be more accurate.
Oxygen potential, oxygen diffusion, and defect equilibria in UO2±x
Authors: Watanabe Masashi , Kato Masato 
Published: January 2023

Since the oxygen potential and the oxygen diffusion coefficient of UO2 have a significant impact on fuel performance, many experimental data have been obtained. However, experimental data of the oxygen potential and the oxygen diffusion coefficient in the high temperature region above 1673 K are very limited. In the present study, we aimed to obtain these data and analyze them by defect chemistry. the oxygen potentials and the oxygen chemical diffusion coefficient of UO2 were measured by the gas equilibrium method in the near stoichiometric region at temperatures ranging from 1673 to 1873 K. A data set of oxygen potentials was made together with literature data and analyzed by defect chemistry. The oxygen potential of UO2 was determined as a function of O/U ratio and temperature, and an equation representing the relationship was derived. The oxygen chemical diffusion coefficient values obtained in this study were reasonably close to the literature values. The oxygen partial pressure dependence of the oxygen chemical diffusion coefficients was predicted from the evaluated results of the oxygen potential data, but no clear dependence was observed.