bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of math abilities before school entry: a tool development
Authors: Cruz Joana , Alves Diana , Carvalho Marisa , Mendes Sofia Abreu , Rodrigues Bruna , Cadime Irene 
Published: January 2024

IntroductionThe years preceding school entry are pivotal for children to develop fundamental skills that bolster their learning in literacy and math in the following years. Skills like counting and subitizing stand as key predictors of future math abilities. Hence, the availability of universal screening tools is vital to promptly identify children who are lacking in these skills, allowing for tailored classroom practices to meet their needs. This study aimed to develop a mathematical screening tool and assess its psychometric properties.MethodsThe tool encompasses both group and individual tasks, to evaluate counting, cardinality, subitizing, quantity discrimination, addition, and subtraction. The tool was administered twice to 257 children, aged 5-6, in their final year of kindergarten in Portugal, at both the start and end of the school year.ResultsThe findings reveal that the tasks generally present a low level of difficulty, especially by the end of kindergarten. Factor analysis demonstrated an adequate structure, and all dimensions showed high internal consistency (&gt;0.80). There was a medium-to-high intercorrelation among the various tasks. Correlations between task scores at the beginning and end of the school year were high. Furthermore, scores across all tasks correlated with math achievement in the first grade of primary education.DiscussionThese outcomes suggest that the tool is both valid and reliable, making it a useful resource for assessing and intervening in math skills during the critical years before school entry.
Renal impairment may indicate postoperative low vision in young patients with proliferative diabetic retinopathy undergoing vitrectomy
Authors: Zheng Xiaorong , Feng Lin , Xing Chen , Wang Junlan , Zhao Wei , Zhang Fengmei 
Published: January 2024

ObjectiveTo innovatively evaluate the impact of renal impairment in young work age patients with proliferative diabetic retinopathy (PDR) on their visuality after vitrectomy.MethodsTo find out whether it is possible to better predict the improvement of visual acuity after vitrectomy in working-age people without adding additional preoperative testing. In view of the fact that diabetic retinopathy and diabetic nephropathy are common diabetic complications of microvascular damage, it is considered whether preoperative renal function can be used as this evaluation index. This paper studies the design under this theme. This retrospective study included 306 patients (306 eyes) diagnosed with PDR and undergoing vitrectomy in our hospital from January 2016 to June 2023. Relevant baseline data were collected, including age, history of kidney disease and clinical laboratory test results. According to the International Standard Logarithmic Visual Acuity Checklist, the best corrected visual acuity was tested on the first day of admission and one month after surgery, and the difference between the two was subtracted. A difference &gt;0 was defined as “vision improved”. Patients were classified as vision-improved group (n=245) and non-improved group (n=61). The differences in baseline serum urea nitrogen, creatinine, uric acid, Cystatin C, estimated glomerular filtration rate (eGFR) and urine protein distribution between the two groups were statistically analyzed, binary regression analysis was performed for meaningful parameters, and random forest model ranked the characteristics in importance.Results1.A higher level of serum cystatin C [1.02(0.80,1.48) mg/L vs 0.86(0.67,1.12) mg/L, P&lt;0.001] and a lower eGFR [82.3(50.33, 115.11) ml/(min/1.73m²) vs 107.69(73.9, 126.01) ml/(min/1.73m²), P=0.002] appeared in the non-(vision-)improved group compared with the vision-improved group. 2. The occurrence of preoperation proteinuria history of nephropathy take a larger proportion in non-improved group. 3. Univariate regression analysis showed history of nephrology (OR=1.887, P=0.028), preoperative serum urea nitrogen (OR=0.939, P=0.043), cystatin C (Cys-C) concentration (OR=0.75, P=0.024), eGFR (OR=1.011, P=0.003) and proteinuria (OR=3.128, P&lt;0.001) were influencing factors to postoperative visual acuity loss in young working age PDR patients. Excluding other confounding factors, preoperative proteinuria is an independent risk factor for postoperative vision improvement in working-age PDR populations (OR=2.722, P=0.009). 4. The accuracy of the prediction random forst model is 0.81. The model appears to be superior in terms of positive prediction.ConclusionIn young work aged PDR patients undergoing vitrectomy, preoperative urine protein can be an independent indicator of postoperative visual loss. Aggressive correction of kidney injury before surgery may help improve postoperative vision in patients with PDR.
Association between human blood metabolome and the risk of delirium: a Mendelian Randomization study
Authors: Long Chubing , Lin Dong , Zhang Lieliang , Lin Yue , Yao Qing , Zhang Guangyong , Li Longshan , Liu Hailin , Ying Jun , Wang Xifeng , Hua Fuzhou 
Published: January 2024

BackgroundDelirium significantly contributes to both mortality and morbidity among hospitalized older adults. Furthermore, delirium leads to escalated healthcare expenditures, extended hospital stays, and enduring cognitive deterioration, all of which are acknowledged detrimental outcomes. Nonetheless, the current strategies for predicting and managing delirium remain constrained. Our aim was to employ Mendelian randomization (MR) to investigate the potential causal relationship between metabolites and delirium, as well as to identify potential therapeutic targets.MethodsWe identified 129 distinct blood metabolites from three genome-wide association studies (GWASs) conducted on the metabolome, involving a total of 147,827 participants of European descent. Genetic information pertaining to delirium was sourced from the ninth iteration of the Finngen Biobank, encompassing 359,699 individuals of Finnish ancestry. We conducted MR analyses to evaluate the connections between blood metabolites and delirium. Additionally, we extended our analysis to encompass the entire phenome using MR, aiming to uncover potential on-target consequences resulting from metabolite interventions.ResultsIn our investigation, we discovered three metabolites serving as causal mediators in the context of delirium: clinical low density lipoprotein cholesterol (LDL-C) (odds ratio [OR]: 1.47, 95% confidence interval [CI]: 1.25-1.73, p = 3.92 x 10-6), sphingomyelin (OR: 1.47, 95% CI: 1.25-1.74, p = 5.97 x 10-6), and X-11593–O-methylascorbate (OR: 0.21, 95% CI: 0.10-0.43, p = 1.86 x 10-5). Furthermore, utilizing phenome-wide MR analysis, we discerned that clinical LDL-C, sphingomyelin, and O-methylascorbate not only mediate delirium susceptibility but also impact the risk of diverse ailments.Limitations(1) Limited representation of the complete blood metabolome, (2) reliance on the PheCode system based on hospital diagnoses may underrepresent conditions with infrequent hospital admissions, and (3) limited to European ancestry.ConclusionThe genetic prediction of heightened O-methylascorbate levels seems to correspond to a diminished risk of delirium, in contrast to the association of elevated clinical LDL-C and sphingomyelin levels with an amplified risk. A comprehensive analysis of side-effect profiles has been undertaken to facilitate the prioritization of drug targets. Notably, O-methylascorbate emerges as a potentially auspicious target for mitigating and treating delirium, offering the advantage of lacking predicted adverse side effects.
Bibliometric and visual analysis of single-cell sequencing from 2010 to 2022
Authors: Chen Ling , Wan Yantong , Yang Tingting , Zhang Qi , Zeng Yuting , Zheng Shuqi , Ling Zhishan , Xiao Yupeng , Wan Qingyi , Liu Ruili , Yang Chun , Huang Guozhi , Zeng Qing 
Published: January 2024

Background: Single-cell sequencing (SCS) is a technique used to analyze the genome, transcriptome, epigenome, and other genetic data at the level of a single cell. The procedure is commonly utilized in multiple fields, including neurobiology, immunology, and microbiology, and has emerged as a key focus of life science research. However, a thorough and impartial analysis of the existing state and trends of SCS-related research is lacking. The current study aimed to map the development trends of studies on SCS during the years 2010–2022 through bibliometric software.Methods: Pertinent papers on SCS from 2010 to 2022 were obtained using the Web of Science Core Collection. Research categories, nations/institutions, authors/co-cited authors, journals/co-cited journals, co-cited references, and keywords were analyzed using VOSviewer, the R package “bibliometric”, and CiteSpace.Results: The bibliometric analysis included 9,929 papers published between 2010 and 2022, and showed a consistent increase in the quantity of papers each year. The United States was the source of the highest quantity of articles and citations in this field. The majority of articles were published in the periodical Nature Communications. Butler A was the most frequently quoted author on this topic, and his article “Integrating single-cell transcriptome data across diverse conditions, technologies, and species” has received numerous citations to date. The literature and keyword analysis showed that studies involving single-cell RNA sequencing (scRNA-seq) were prominent in this discipline during the study period.Conclusion: This study utilized bibliometric techniques to visualize research in SCS-related domains, which facilitated the identification of emerging patterns and future directions in the field. Current hot topics in SCS research include COVID-19, tumor microenvironment, scRNA-seq, and neuroscience. Our results are significant for scholars seeking to identify key issues and generate new research ideas.
Case Report: From epilepsy and uterus didelphys to Turner syndrome-associated dysgerminoma
Authors: Li Jinghua , Zhu Haipeng , Ma Xuelian , Li Jia , Xue Jing , Feng Limin 
Published: January 2024

Dysgerminoma is a rare occurrence in Turner syndrome patients without Y chromosome mosaicism or hormone therapy during puberty. We present a unique case of a 33-year-old nulliparous Chinese woman with intermittent epilepsy and Mullerian anomalies carrying a double uterus, cervix, and vagina. The patient is also characterized as having Turner syndrome accompanied by 46,X, del(Xp22.33-11.23) and del(2)(q11.1-11.2). MRI exhibited a 17.0 cm × 20.0 cm × 10.5 cm solid ovarian lesion. Radical surgery and pathology revealed dysgerminoma at stage IIIc with lymphatic metastases and a KIT gene mutation identified in exon 13. Furthermore, the tumor microenvironment (TME) displayed robust expression of CD4+ T lymphocytes and PD-1, whereas the distribution of CD8+ T lymphocytes and PDL-1 was sporadic. Despite the administration of enoxaparin to prevent thromboembolism, the patient experienced multiple cerebral infarctions during chemotherapy. Subsequently, the patient chose to decline further treatment and was discharged. This exceptional case imparts several noteworthy lessons. First, the coexistence of Mullerian anomalies, although rare, is not incompatible with Turner syndrome. Second, screening for KIT mutations is imperative to reduce the risk of dysgerminoma in Turner syndrome, especially for patients with Y mosaicism who are recommended for hormone replacement therapy. Lastly, comprehensive anticoagulation therapy is crucial for Turner syndrome patients undergoing cisplatin-based chemotherapy.
Empirical validation of ProteinMPNN’s efficiency in enhancing protein fitness
Authors: Wang Tianshu , Jin Xiaocheng , Lu Xiaoli , Min Xiaoping , Ge Shengxiang , Li Shaowei 
Published: January 2024

Introduction: Protein engineering, which aims to improve the properties and functions of proteins, holds great research significance and application value. However, current models that predict the effects of amino acid substitutions often perform poorly when evaluated for precision. Recent research has shown that ProteinMPNN, a large-scale pre-training sequence design model based on protein structure, performs exceptionally well. It is capable of designing mutants with structures similar to the original protein. When applied to the field of protein engineering, the diverse designs for mutation positions generated by this model can be viewed as a more precise mutation range.Methods: We collected three biological experimental datasets and compared the design results of ProteinMPNN for wild-type proteins with the experimental datasets to verify the ability of ProteinMPNN in improving protein fitness.Results: The validation on biological experimental datasets shows that ProteinMPNN has the ability to design mutation types with higher fitness in single and multi-point mutations. We have verified the high accuracy of ProteinMPNN in protein engineering tasks from both positive and negative perspectives.Discussion: Our research indicates that using large-scale pre trained models to design protein mutants provides a new approach for protein engineering, providing strong support for guiding biological experiments and applications in biotechnology.
Germinal centers are permissive to subdominant antibody responses
Authors: Robert Philippe A. , Arulraj Theinmozhi , Meyer-Hermann Michael 
Published: January 2024

IntroductionA protective humoral response to pathogens requires the development of high affinity antibodies in germinal centers (GC). The combination of antigens available during immunization has a strong impact on the strength and breadth of the antibody response. Antigens can display various levels of immunogenicity, and a hierarchy of immunodominance arises when the GC response to an antigen dampens the response to other antigens. Immunodominance is a challenge for the development of vaccines to mutating viruses, and for the development of broadly neutralizing antibodies. The extent by which antigens with different levels of immunogenicity compete for the induction of high affinity antibodies and therefore contribute to immunodominance is not known.MethodsHere, we perform in silico simulations of the GC response, using a structural representation of antigens with complex surface amino acid composition and topology. We generate antigens with complex domains of different levels of immunogenicity and perform simulations with combinations of these domains.ResultsWe found that GC dynamics were driven by the most immunogenic domain and immunodominance arose as affinity maturation to less immunogenic domain was inhibited. However, this inhibition was moderate since the less immunogenic domain exhibited a weak GC response in the absence of the most immunogenic domain. Less immunogenic domains reduced the dominance of GC responses to more immunogenic domains, albeit at a later time point.DiscussionThe simulations suggest that increased vaccine valency may decrease immunodominance of the GC response to strongly immunogenic domains and therefore, act as a potential strategy for the natural induction of broadly neutralizing antibodies in GC reactions.
Examining the function of macrophage oxidative stress response and immune system in glioblastoma multiforme through analysis of single-cell transcriptomics
Authors: Xing Jin , Cai Huabao , Lin Zhiheng , Zhao Liang , Xu Hao , Song Yanbing , Wang Zhihan , Liu Chaobo , Hu Guangdong , Zheng Jiajie , Ren Li , Wei Zilong 
Published: January 2024

BackgroundGlioblastoma (GBM), a prevalent malignant neoplasm within the neuro-oncological domain, has been a subject of considerable scrutiny. Macrophages, serving as the principal immunological constituents, profoundly infiltrate the microenvironment of GBM. However, investigations elucidating the intricate immunological mechanisms governing macrophage involvement in GBM at the single-cell level remain notably limited.MethodsWe conducted a comprehensive investigation employing single-cell analysis, aiming to redefine the intricate cellular landscape within both the core and peripheral regions of GBM tumors. Our analytical focus extended to the profound study of macrophages, elucidating their roles within the context of oxidative stress, intercellular information exchange, and cellular trajectories concerning GBM and its assorted subpopulations. We pursued the identification of GBM prognostic genes intricately associated with macrophages. Utilizing experimental research to investigate the relevance of MANBA in the context of GBM.ResultsOur investigations have illuminated the central role of macrophages in the intricate interplay among various subpopulations within the GBM microenvironment. Notably, we observed a pronounced intensity of oxidative stress responses within macrophages when compared to their GBM counterparts in other subpopulations. Moreover, macrophages orchestrated intricate cellular communication networks, facilitated by the SPP1-CD44 axis, both internally and with neighboring subpopulations. These findings collectively suggest the potential for macrophage polarization from an M1 to an M2 phenotype, contributing to immune suppression within the tumor microenvironment. Furthermore, our exploration unearthed GBM prognostic genes closely associated with macrophages, most notably MANBA and TCF12. Remarkably, MANBA appears to participate in the modulation of neuroimmune functionality by exerting inhibitory effects on M1-polarized macrophages, thereby fostering tumor progression. To bolster these assertions, experimental validations unequivocally affirmed the promotional impact of MANBA on GBM, elucidated through its capacity to curb cell proliferation, invasiveness, and metastatic potential.ConclusionThese revelations represent a pivotal step towards unraveling the intricate immunological mechanisms governing the interactions between macrophages and diverse subpopulations within the GBM milieu. Furthermore, they lay the foundation for the development of an innovative GBM prognostic model, with MANBA at its epicenter, and underscore the potential for novel immunotherapeutic targets in the ongoing pursuit of enhanced treatment modalities for this formidable malignancy.
Case report: Apalutamide-induced severe lethal cutaneous adverse effects in China
Authors: Wang Qi , Cao Huali , Zhang Xuetong , Wu Huifeng , Tang Zhuangli 
Published: January 2024

IntroductionApalutamide is a novel agent for castration-resistant prostate cancer while skin rashes are the most common untoward reactions. Up to now, most of the reported dermatologic adverse events (dAEs) allocated to mild and moderate with a fair prognosis. Herein, we report a case series of severe dAEs in China caused by apalutamide.Case presentationThe four patients all developed severe and lethal drug eruptions including Stevens-Johnson syndrome and toxic epidermal necrolysis with a mean incubation period of 40 days. On the basis of the medical condition, all the patients were suggested to withdraw apalutamide and three of them recovered. Of note, attempts of rechallenges of apalutamide may be fatal.DiscussionThe incidence of dAEs in previously conducted clinical trials exceeded 20%, with maculopapular rashes being the most common feature. However, the incidence and severity varied in different geographic regions and ethnicities. Inadequate attention was paid to severe cutaneous adverse reactions. Long latency may easily lead to the misdiagnosis of dAEs, and immediate withdrawal of apalutamide is the cornerstone of therapies.ConclusionSpecial and adequate attention should be paid to apalutamide-attributed severe cutaneous adverse effects. Besides, the prognosis of severe drug eruptions may be disappointing, and in-time withdrawal is vital.
High-grade synovitis associates with clinical markers and response to therapy in chronic inflammatory arthritis: post hoc analysis of a synovial biomarkers prospective cohort study
Authors: Garaffoni Carlo , Tamussin Marianna , Calciolari Ilaria , Lanza Giovanni , Bortoluzzi Alessandra , Scirè Carlo Alberto , Govoni Marcello , Silvagni Ettore 
Published: January 2024

BackgroundInflammatory arthritis (IAs), such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA), are characterized by the presence of chronic synovitis. The Krenn’s synovitis score (KSS), a simple tool detectable by haematoxylin/eosin staining of synovial biopsy samples, allows the discrimination between high-grade and low-grade synovitis. The aim of this study was to identify the clinical associations of KSS and to evaluate the relationship between high-grade synovitis and treatment response in IA patients.MethodsClinical, laboratory and ultrasound data were retrieved from RA and PsA patients recruited in the prospective MATRIX cohort study. Inclusion criteria were age≥18 years, RA or PsA diagnosis, and presence of active disease with eligibility to start/modify therapy. Patients underwent ultrasound-guided synovial biopsy of one of the most involved joints before starting/modifying treatment according to treat-to-target strategy. The samples were analysed by an expert pathologist for KSS calculation. Univariable and multivariable logistic regression analyses were performed to evaluate the relationship between KSS and baseline variables. The association between KSS and treatment response at 24 weeks of follow-up was investigated in univariable logistic regression analysis.Results53 patients, 34 RA and 19 PsA, completed 24 weeks of follow-up after synovial biopsy. Patients were either treatment naïve (N=6, 11%), csDMARDs-experienced (N=46, 87%) or b/tsDMARDs-experienced (N=20, 38%). Median KSS was 6.00 (Q1-Q3 4.00-7.00) in RA and 4.00 (3.00-6.00) in PsA (p=0.040), and inflammatory infiltrates score was significantly higher in RA than in PsA patients (median 3.00 vs 2.00, p=0.021). In multivariable analysis, synovial effusion in the biopsied joint (OR 9.26, 95%CI 2.12-53.91) and erythrocyte sedimentation rate (ESR) (OR 1.04, 95%CI 1.01-1.08) associated with high KSS. High-grade synovitis significantly associated with a higher probability of achieving DAS28 remission, ACR20/50 response, and Boolean2.0 remission, independently from diagnosis.ConclusionSeveral markers of pro-inflammatory pathways associated with the presence of high-grade synovitis, and patients with higher KSS shared a higher probability of treatment targets achievement in the follow up. The integration of a simple and feasible tool like KSS in the clinical and prognostic stratification of patients with IA might help in intercepting patients with a disease more prone to respond to available treatment paradigms.