bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myositis-associated antibodies predict the severity of lung involvement in adult patients with inflammatory myositis − a cohort study of 70 adult patients with myositis in a single center
Authors: Marklund Josefin , Hanna Balsam , Jin Tao , Pullerits Rille 
Published: March 2024

IntroductionIdiopathic inflammatory myopathies (IIMs) encompass a diverse group of diseases characterized by considerable variability in clinical manifestations, antibody profiles, and responsiveness to immunosuppressive therapies. This study aimed to investigate the association between organ involvement and distinct myositis autoantibodies in individuals with IIM in a single-center cohort.MethodsPatients with ICD diagnoses M33.1, M33.2, M33.9, or M609 who (1) had been tested with Euroline blot assay for myositis autoantibodies and (2) met the classification criteria of definite/probable polymyositis (PM) or dermatomyositis (DM), anti-synthetase syndrome (ASS), or inclusion body myositis (IBM) were included. Medical journals were retrospectively examined with respect to clinical disease features.ResultsSeventy patients (median age 58 years; 66% females) were included and represented the following diagnosis: PM (n = 23), DM (n = 21), ASS (n = 23), and IBM (n = 3). Most of the patients (87%) presented a muscle biopsy indicative of myositis. The presence of autoantibodies was as follows: myositis-specific antibodies, MSA (n = 53), myositis-associated antibodies, MAA (n = 33), both MSA + MAA (n = 24), MSA only (n = 29), MAA only (n = 9), no MSA, or MAA (n = 8). Anti-Jo-1 was the most common MSA (19%), whereas the most common MAA was anti-Ro/SSA52 (31%). We observed a significant association between antibody patterns and lung disease. In our cohort, 47% of the patients in the whole study group, 86% of patients with anti-SSA52, and 100% with anti-Jo-1 had pulmonary involvement. Patients with both MSA and MAA had a higher incidence of lung disease and decreased CO-diffusion capacity. This was especially prominent in anti-Ro/SSA52-positive patients. Interestingly, none of the patients suffered from lung disease if only antibodies against Mi-2α, Mi-2β, NXP2, HMGCR, and TIF1γ were present or no MSA/MAA were detected.Discussion:The simultaneous presence of both MAA and MSA indicates an increased risk of lung involvement in patients with inflammatory myopathies. The presence of any MAA, and especially anti-Ro/SSA52, is associated with more severe pulmonary disease. Our data suggest that MAA antibodies might be relevant markers for early detection and treatment of lung involvement in IIM.
Innovative research methodologies in the EU regulatory framework: an analysis of EMA qualification procedures from a pediatric perspective
Authors: Giannuzzi Viviana , Bertolani Arianna , Torretta Silvia , Reggiardo Giorgio , Toich Eleonora , Bonifazi Donato , Ceci Adriana 
Published: March 2024

IntroductionThe European Medicines Agency (EMA) offers scientific advice to support the qualification procedure of novel methodologies, such as preclinical and in vitro models, biomarkers, and pharmacometric methods, thereby endorsing their acceptability in medicine research and development (R&amp;D). This aspect is particularly relevant to overcome the scarcity of data and the lack of validated endpoints and biomarkers in research fields characterized by small samples, such as pediatrics.AimThis study aimed to analyze the potential pediatric interest in methodologies qualified as “novel methodologies for medicine development” by the EMA.MethodsThe positive qualification opinions of novel methodologies for medicine development published on the EMA website between 2008 and 2023 were identified. Multi-level analyses were conducted to investigate data with a hierarchical structure and the effects of cluster-level variables and cluster-level variances and to evaluate their potential pediatric interest, defined as the possibility of using the novel methodology in pediatric R&amp;D and the availability of pediatric data. The duration of the procedure, the type of methodology, the specific disease or disease area addressed, the type of applicant, and the availability of pediatric data at the time of the opinion release were also investigated.ResultsMost of the 27 qualifications for novel methodologies issued by the EMA (70%) were potentially of interest to pediatric patients, but only six of them reported pediatric data. The overall duration of qualification procedures with pediatric interest was longer than that of procedures without any pediatric interest (median time: 7 months vs. 3.5 months, respectively; p = 0.082). In parallel, qualification procedures that included pediatric data lasted for a longer period (median time: 8 months vs. 6 months, respectively; p = 0.150). Nephrology and neurology represented the main disease areas (21% and 16%, respectively), while endpoints, biomarkers, and registries represented the main types of innovative methodologies (32%, 26%, and 16%, respectively).DiscussionOur results underscore the importance of implementing innovative methodologies in regulatory-compliant pediatric research activities. Pediatric-dedicated research infrastructures providing regulatory support and strategic advice during research activities could be crucial to the design of ad hoc pediatric methodologies or to extend and validate them for pediatrics.
Characteristics of SARS-CoV-2 Omicron BA.5 variants in Shanghai after ending the zero-COVID policy in December 2022: a clinical and genomic analysis
Authors: Liu Pengcheng , Cai Jiehao , Tian He , Li Jingjing , Lu Lijuan , Xu Menghua , Zhu Xunhua , Fu Xiaomin , Wang Xiangshi , Zhong Huaqing , Jia Ran , Ge Yanling , Zhu Yanfeng , Zeng Mei , Xu Jin 
Published: March 2024

IntroductionAn unprecedented surge of Omicron infections appeared nationwide in China in December 2022 after the adjustment of the COVID-19 response policy. Here, we report the clinical and genomic characteristics of SARS-CoV-2 infections among children in Shanghai during this outbreak.MethodsA total of 64 children with symptomatic COVID-19 were enrolled. SARS-CoV-2 whole genome sequences were obtained using next-generation sequencing (NGS) technology. Patient demographics and clinical characteristics were compared between variants. Phylogenetic tree, mutation spectrum, and the impact of unique mutations on SARS-CoV-2 proteins were analysed in silico.ResultsThe genomic monitoring revealed that the emerging BA.5.2.48 and BF.7.14 were the dominant variants. The BA.5.2.48 infections were more frequently observed to experience vomiting/diarrhea and less frequently present cough compared to the BF.7.14 infections among patients without comorbidities in the study. The high-frequency unique non-synonymous mutations were present in BA.5.2.48 (N:Q241K) and BF.7.14 (nsp2:V94L, nsp12:L247F, S:C1243F, ORF7a:H47Y) with respect to their parental lineages. Of these mutations, S:C1243F, nsp12:L247F, and ORF7a:H47Y protein were predicted to have a deleterious effect on the protein function. Besides, nsp2:V94L and nsp12:L247F were predicted to destabilize the proteins.DiscussionFurther in vitro to in vivo studies are needed to verify the role of these specific mutations in viral fitness. In addition, continuous genomic monitoring and clinical manifestation assessments of the emerging variants will still be crucial for the effective responses to the ongoing COVID-19 pandemic.
Frequency-dependent alterations in functional connectivity in patients with Alzheimer’s Disease spectrum disorders
Authors: Hu Hanjun , Wang Luoyu , Abdul Sammad , Tang Xue , Feng Qi , Mu Yuzhu , Ge Xiuhong , Liao Zhengluan , Ding Zhongxiang 
Published: March 2024

BackgroundIn the spectrum of Alzheimer’s Disease (AD) and related disorders, the resting-state functional magnetic resonance imaging (rs-fMRI) signals within the cerebral cortex may exhibit distinct characteristics across various frequency ranges. Nevertheless, this hypothesis has not yet been substantiated within the broader context of whole-brain functional connectivity. This study aims to explore potential modifications in degree centrality (DC) and voxel-mirrored homotopic connectivity (VMHC) among individuals with amnestic mild cognitive impairment (aMCI) and AD, while assessing whether these alterations differ across distinct frequency bands.MethodsThis investigation encompassed a total of 53 AD patients, 40 aMCI patients, and 40 healthy controls (HCs). DC and VMHC values were computed within three distinct frequency bands: classical (0.01–0.08 Hz), slow-4 (0.027–0.073 Hz), and slow-5 (0.01–0.027 Hz) for the three respective groups. To discern differences among these groups, ANOVA and subsequent post hoc two-sample t-tests were employed. Cognitive function assessment utilized the mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA). Pearson correlation analysis was applied to investigate the associations between MMSE and MoCA scores with DC and VMHC.ResultsSignificant variations in degree centrality (DC) were observed among different groups across diverse frequency bands. The most notable differences were identified in the bilateral caudate nucleus (CN), bilateral medial superior frontal gyrus (mSFG), bilateral Lobule VIII of the cerebellar hemisphere (Lobule VIII), left precuneus (PCu), right Lobule VI of the cerebellar hemisphere (Lobule VI), and right Lobule IV and V of the cerebellar hemisphere (Lobule IV, V). Likewise, disparities in voxel-mirrored homotopic connectivity (VMHC) among groups were predominantly localized to the posterior cingulate gyrus (PCG) and Crus II of the cerebellar hemisphere (Crus II). Across the three frequency bands, the brain regions exhibiting significant differences in various parameters were most abundant in the slow-5 frequency band.ConclusionThis study enhances our understanding of the pathological and physiological mechanisms associated with AD continuum. Moreover, it underscores the importance of researchers considering various frequency bands in their investigations of brain function.
Analysis of risk factors related to the progression rate of hemifacial spasm
Authors: Xu Fei , Gu Pengju , Yuan Huan , Jiang Li , Xie Yanfeng , Shi Quanhong , Zhan Yan 
Published: March 2024

IntroductionAlthough there have been many researches on the etiology and risk factors with the onset of hemifacial spasm, researches on the risk factors related to progression rate are limited. This study aims to analyze the risk factors related to the progression rate of hemifacial spasm.MethodsThe study enrolled 142 patients who underwent microvascular decompression for hemifacial spasm. Based on the duration and severity of symptoms, patients were classified into rapid progression group and slow progression group. To analyze risk factors, univariate and multivariate logistic regression analyses were conducted. Of 142 patients with hemifacial spasm, 90(63.3%) were classified as rapid progression group, 52(36.7%) were classified as slow progression group.ResultsIn the univariate analysis, there were significant statistical differences between the two groups in terms of age of onset (P = 0.021), facial nerve angle (P &lt; 0.01), hypertension (P = 0.01), presence of APOE ε4 expression (P &lt; 0.01) and different degrees of brainstem compression in the Root Entry Zone (P &lt; 0.01). In the multivariable analyses, there were significant statistical differences between the two groups in terms of age of symptom onset (P &lt; 0.01 OR = 6.591), APOE ε4 (P &lt; 0.01 OR = 5.691), brainstem compression (P = 0.006 OR = 5.620), and facial nerve angle (P &lt; 0.01 OR = 5.758). Furthermore, we found no significant correlation between the severity of facial spasms and the progression rate of the disease (t = 2.47, P = 0.12&gt;0.05).ConclusionAccording to our study, patients with facial nerve angle ≤ 96.5°, severer compression of the brainstem by offending vessels, an onset age &gt; 45 years and positive expression of APOE ε4, may experience faster progression of hemifacial spasm.
Graph neural network based on brain inspired forward-forward mechanism for motor imagery classification in brain-computer interfaces
Authors: Xue Qiwei , Song Yuntao , Wu Huapeng , Cheng Yong , Pan Hongtao 
Published: March 2024

IntroductionWithin the development of brain-computer interface (BCI) systems, it is crucial to consider the impact of brain network dynamics and neural signal transmission mechanisms on electroencephalogram-based motor imagery (MI-EEG) tasks. However, conventional deep learning (DL) methods cannot reflect the topological relationship among electrodes, thereby hindering the effective decoding of brain activity.MethodsInspired by the concept of brain neuronal forward-forward (F-F) mechanism, a novel DL framework based on Graph Neural Network combined forward-forward mechanism (F-FGCN) is presented. F-FGCN framework aims to enhance EEG signal decoding performance by applying functional topological relationships and signal propagation mechanism. The fusion process involves converting the multi-channel EEG into a sequence of signals and constructing a network grounded on the Pearson correlation coeffcient, effectively representing the associations between channels. Our model initially pre-trains the Graph Convolutional Network (GCN), and fine-tunes the output layer to obtain the feature vector. Moreover, the F-F model is used for advanced feature extraction and classification.Results and discussionAchievement of F-FGCN is assessed on the PhysioNet dataset for a four-class categorization, compared with various classical and state-of-the-art models. The learned features of the F-FGCN substantially amplify the performance of downstream classifiers, achieving the highest accuracy of 96.11% and 82.37% at the subject and group levels, respectively. Experimental results affirm the potency of FFGCN in enhancing EEG decoding performance, thus paving the way for BCI applications.
Computer modeling of digestive processes in the alimentary tract and their physiological regulation mechanisms: closing the gap between digestion models and in vivo behavior
Authors: van Aken George A. 
Published: March 2024

IntroductionA model has been developed for in silico simulation of digestion and its physiological feedback mechanisms.MethodsThe model is based on known physiology described in the literature and is able to describe the complexity of many simultaneous processes related to food digestion.ResultsDespite the early stage of development of the model, it already encompasses a large number of processes that occur simultaneously, enabling the prediction of a large number of post-prandial physiological markers, which can be highly functional in combination with in vitro, organ-on-a-chip and digital twin models purposed to measure the physiological properties of organs and to predict the effect of adjusted food composition in normal and diseased states.DiscussionInput from and collaboration between science fileds is needed to further develop and refine the model and to connect with in vitro, in vivo, and ex vivo (organ-on-a-chip) models.
A refined prediction model for survival in hepatocellular carcinoma patients treated with transarterial chemoembolization
Authors: Lee Hae Lim , Kim Seok Hwan , Kim Hee Yeon , Lee Sung Won , Song Myeong Jun 
Published: March 2024

Background/AimsTransarterial chemoembolization (TACE) is widely performed as a major treatment for hepatocellular carcinoma (HCC) patients, and there is a need to stratify patients for whom the most benefit from the treatment. This study aimed to develop a refined prediction model for overall survival (OS) in patients undergoing TACE as a first-line treatment in a large cohort and validate its performance.MethodsA total of 2,632 patients with HCC of Barcelona Clinic Liver Cancer stage A or B who underwent TACE between 2008 and 2017 were enrolled. The patients were randomly assigned to a training cohort (n = 1,304) or a validation cohort (n = 1,328). Independent predictors of OS were used to develop a prediction model.ResultsThe median age of patients in the entire cohort was 63 years, with the majority having hepatitis B virus (56.6%) and being classified as Child-Pugh class A (82.4%). We developed a new prognostic model, called the TACE-prognostic (TP) score, based on tumor burden (sum of the largest tumor diameter and tumor number), alpha-fetoprotein, and Albumin-Bilirubin grade. Patients were classified into five risk groups according to TP scores, with median survival significantly differentiated in both training and validation cohorts (P &lt; 0.001). The new model consistently outperformed other currently available models in both the training and validation cohorts.ConclusionThis newly developed TP scoring system has the potential to be a useful tool in identifying ideal candidates of TACE and predicting OS with favorable performance and discrimination. However, further external validation is needed to confirm its effectiveness.
Osimertinib in the treatment of resected EGFR-mutated non-small cell lung cancer: a cost-effectiveness analysis in the United States
Authors: Huo Gengwei , Song Ying , Liu Wenjie , Cao Xuchen , Chen Peng 
Published: March 2024

Background: In the double-blind phase III ADAURA randomized clinical trial, adjuvant osimertinib showed a substantial overall survival benefit in patients with stage IB to IIIA, EGFR-mutated, completely resected non-small cell lung cancer (NSCLC). We conduct a cost-effectiveness analysis comparing the use of adjuvant osimertinib to placebo in patients with stage IB to IIIA, EGFR-mutated, resected NSCLC.Methods: Based on the results obtained from the ADAURA trial, a Markov model with three-state was employed to simulate patients who were administered either osimertinib or placebo until disease recurrence or completion of the study period (3 years). Quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER) were calculated with a willingness-to-pay (WTP) threshold of $150,000 per QALY. Both univariate and probabilistic sensitivity analyses were carried out to explore the robustness of the model.Results: Osimertinib produced additional 1.59 QALYs with additional costs of $492,710 compared to placebo, giving rise to ICERs of $309,962.66/QALY. The results of the univariate sensitivity analysis indicated that the utility of disease-free survival (DFS), cost of osimertinib, and discount rate had the greatest impact on the outcomes. Probabilistic sensitivity analysis showed that osimertinib exhibited a 0% chance of being considered cost-effective for patients using a WTP threshold $150,000/QALY.Conclusion: In our model, osimertinib was unlikely to be cost-effective compared to placebo for stage IB to IIIA, EGFR-mutated, completely resected NSCLC patients from the perspective of a U.S. payer at a WTP threshold of $150,000 per QALY.
Pollen transcriptomic analysis provided insights into understanding the molecular mechanisms underlying grafting-induced improvement in potato fertility
Authors: Zhang Xing , Bai Lei , Li Maoxing , Li Youhan , Hu Ronghai , Guo Huachun 
Published: March 2024

IntroductionHeterologous grafting has been proven to be a valid approach to improving potato fertility, especially when grafting potatoes with other Solanaceae family plants. However, the mechanisms underlying grafting-induced improvement in potato fertility are still unknown.MethodsIn this study, a poor-fertility potato cultivar “Qingshu No. 9” (Q9) was grafted with a tomato cultivar “Zhongyan988” (ZY988) to study the effects of heterologous grafting in the former. The tuber yield was controlled by different grafting and cultivation approaches, and the correlation between tuber yield and pollen vigor was studied. Comparative transcriptomic analysis of the potential mechanisms of pollen in potato scion fertility changes.ResultGrafting with the tomato rootstock effectively promoted the flower and fruit formation in the scion potato and improved its pollen viability by 15%–20%. In addition, a significant negative correlation was observed between the potato tuber yield and pollen viability, suggesting a potential impact on the metabolic regulatory network related to tuber formation. From the comparative transcriptomic analysis between the pollens from Q9 self-grafted plants and Q9-tomato grafting scion, 513 differentially expressed genes (DEGs) were identified. These DEGs were found to be related to gametophyte and pollen development, carbohydrate metabolism, and protein processing. Thus, these DEGs might be involved in improved fertility after reduced tuberization in plants subjected to heterologous grafting.DiscussionPotato/tomato heterologous grafting significantly improved the pollen viability of scion potatoes and was associated with the absence of potato tubers. Heterologous grafting promotes the transcription of genes related to protein processing, carbohydrate metabolism, and pollen development in pollen cells, resulting in the production of fertile pollen. Our results provided initial clues to understanding the improvement of potato fertility using the heterologous grafting method, which might be a useful tool in assisted potato breeding.
Exploring the similarities between risk factors triggering depression in humans and elevated in-cage “inactive but awake” behavior in laboratory mice
Authors: Schmitt Oceane , Finnegan Emily , Trevarthen Anna , Wongsaengchan Chanakarn , Paul Elizabeth S. , Mendl Michael , Fureix Carole 
Published: March 2024

IntroductionDepression is a human mental disorder that can also be inferred in non-human animals. This study explored whether time spent inactive but awake (“IBA”) in the home-cage in mice was further triggered by risk factors similar to those increasing vulnerability to depression in humans (early life stress, genetic predispositions, adulthood stress).MethodsEighteen DBA/2 J and 18 C57BL/6 J females were tested, of which half underwent as pups a daily maternal separation on post-natal days 2–14 (early-life stress “ELS”) (other half left undisturbed). To assess the effect of the procedure, the time the dams from which the 18 subjects were born spent active in the nest (proxy for maternal behavior) was recorded on post-natal days 2, 6, 10 and 14 for 1 h before separation and following reunion (matched times for controls), using live instantaneous scan sampling (total: 96 scans/dam). For each ELS condition, about half of the pups were housed post-weaning (i.e., from 27 days old on average) in either barren (triggering IBA and depression-like symptoms) or larger, highly enriched cages (n = 4–5 per group). Time mice spent IBA post-weaning was observed blind to ELS treatment using live instantaneous scan sampling in two daily 90-min blocks, two days/week, for 6 weeks (total: 192 scans/mouse). Data were analyzed in R using generalized linear mixed models.ResultsThe dams were significantly more active in the nest over time (p = 0.016), however with no significant difference between strains (p = 0.18), ELS conditions (p = 0.20) and before/after separation (p = 0.83). As predicted, post-weaning barren cages triggered significantly more time spent IBA in mice than enriched cages (p &lt; 0.0001). However, neither ELS (p = 0.4) nor strain (p = 0.84) significantly influenced time mice spent IBA, with no significant interaction with environmental condition (ELS × environment: p = 0.2861; strain × environment: p = 0.5713).DiscussionOur results therefore only partly support the hypothesis that greater time spent IBA in mice is triggered by risk factors for human depression. We discuss possible explanations for this and further research directions.