bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rhes depletion promotes striatal accumulation and aggregation of mutant huntingtin in a presymptomatic HD mouse model
Authors: Pan Yongcheng , Tang Beisha , Li Xiao-Jiang , Li Shihua , Liu Qiong 
Published: August 2023

IntroductionHuntington’s disease (HD) is caused by CAG trinucleotide repeats in the HTT gene. Selective neurodegeneration in the striatum is prominent in HD, despite widespread expression of mutant HTT (mHTT). Ras homolog enriched in the striatum (Rhes) is a GTP-binding protein enriched in the striatum, involved in dopamine-related behaviors and autophagy regulation. Growing evidence suggests Rhes plays a critical role in the selective striatal degeneration in HD, but its specific function in this context remains complex and controversial.MethodsIn this study, we utilized CRISPR/Cas9 to knockdown Rhes at different disease stages through adeno-associated virus (AAV) transduction in HD knock-in (KI) mice. Immunoblotting and immunofluorescence were employed to assess the impact of Rhes depletion on mHTT levels, neuronal loss, astrogliosis and autophagy activity.ResultsRhes depletion in 22-week-old HD KI mice (representing the presymptomatic stage) led to mHTT accumulation, reduced neuronal cell staining, and increased astrogliosis. However, no such effects were observed in 36-week-old HD KI mice (representing the symptomatic stage). Additionally, Rhes deletion in 22-week-old HD KI mice resulted in increased P62 levels, reduced LC3-II levels, and unchanged phosphorylation of mTOR and beclin-1, unchanged mTOR protein level, except for a decrease in beclin-1.DiscussionOur findings suggest that knockdown Rhes promotes striatal aggregation of mutant huntingtin by reducing autophagy activity in a mTOR-independent manner. Rhes plays a protective role during the presymptomatic stage of HD KI mice.
Validity of the telematic Fugl Meyer assessment scale – upper extremity (TFMA-UE) Spanish version
Authors: Llamas-Ramos Rocío , Llamas-Ramos Inés , Pérez-Robledo Fátima , Sánchez-González Juan Luis , Bermejo-Gil Beatriz María , Frutos-Bernal Elisa , Martín-Nogueras Ana María 
Published: August 2023

BackgroundTelematic assistance has become indispensable in recent years. The increased prevalence of Acquired brain injury and the sequels it causes, requires long–lasting multidisciplinary treatments. Validated tools to assess the evolution of the disabilities and limitations of this pathology are essential to individualize and prescribe adapted treatments. The aim has been to create the telematic version of the Fugl Meyer Assessment-Upper Extremity Motor Function (TFMA-UE) Spanish scale and its adaptation to the remote assessment of neurologic patients.MethodsAn adapted scale was designed based on the Fugl Meyer Assessment scale-telematic version (FMA-TV): TFMA-UE. This scale is composed by 21 items which evaluate the upper extremity motor function. Physiotherapists trained in this tool, evaluate the results obtained from applying the two versions (on-site and telematic) to compare the results.ResultsTFMA-UE was administered to 30 patients with acquired brain injury. It was applied on site and through the web platform selected by the patients in two different days. Patients completed all the scale in an easily way without help. The exploratory and confirmatory factor analysis confirmed a factorial structure with a factor (76.08% of the variance). The Cronbach’s internal consistency index obtained was 0.98 and the weight kappa index used to measure agreement between the two versions was 0.78 which represents substantial agreement.ConclusionThe Telematic Fugl Meyer Assessment-Upper Extremity Motor Function (TFMA-UE) scale is a viable, useful and easy to apply tool that allows the upper extremity motor function assessment of Acquired Brain Injury patients.
How do patients with Parkinson’s disease and cerebellar ataxia read aloud? -Eye–voice coordination in text reading
Authors: Terao Yasuo , Tokushige Shin-ichi , Inomata-Terada Satomi , Miyazaki Tai , Kotsuki Naoki , Fisicaro Francesco , Ugawa Yoshikazu 
Published: August 2023

BackgroundThe coordination between gaze and voice is closely linked when reading text aloud, with the gaze leading the reading position by a certain eye–voice lead (EVL). How this coordination is affected is unknown in patients with cerebellar ataxia and parkinsonism, who show oculomotor deficits possibly impacting coordination between different effectors.ObjectiveTo elucidate the role of the cerebellum and basal ganglia in eye–voice coordination during reading aloud, by studying patients with Parkinson’s disease (PD) and spinocerebellar degeneration (SCD).MethodsParticipants were sixteen SCD patients, 18 PD patients, and 30 age-matched normal subjects, all native Japanese speakers without cognitive impairment. Subjects read aloud Japanese texts of varying readability displayed on a monitor in front of their eyes, consisting of Chinese characters and hiragana (Japanese phonograms). The gaze and voice reading the text was simultaneously recorded by video-oculography and a microphone. A custom program synchronized and aligned the gaze and audio data in time.ResultsReading speed was significantly reduced in SCD patients (3.53 ± 1.81 letters/s), requiring frequent regressions to compensate for the slow reading speed. In contrast, PD patients read at a comparable speed to normal subjects (4.79 ± 3.13 letters/s vs. 4.71 ± 2.38 letters/s). The gaze scanning speed, excluding regressive saccades, was slower in PD patients (9.64 ± 4.26 letters/s) compared to both normal subjects (12.55 ± 5.42 letters/s) and SCD patients (10.81 ± 4.52 letters/s). PD patients’ gaze could not far exceed that of the reading speed, with smaller allowance for the gaze to proceed ahead of the reading position. Spatial EVL was similar across the three groups for all texts (normal: 2.95 ± 1.17 letters/s, PD: 2.95 ± 1.51 letters/s, SCD: 3.21 ± 1.35 letters/s). The ratio of gaze duration to temporal EVL was lowest for SCD patients (normal: 0.73 ± 0.50, PD: 0.70 ± 0.37, SCD: 0.40 ± 0.15).ConclusionAlthough coordination between voice and eye movements and normal eye-voice span was observed in both PD and SCD, SCD patients made frequent regressions to manage the slowed vocal output, restricting the ability for advance processing of text ahead of the gaze. In contrast, PD patients experience restricted reading speed primarily due to slowed scanning, limiting their maximum reading speed but effectively utilizing advance processing of upcoming text.
From signals to music: a bottom-up approach to the structure of neuronal activity
Authors: Noel Gabriel D. , Mugno Lionel E. , Andres Daniela S. 
Published: August 2023

IntroductionThe search for the “neural code” has been a fundamental quest in neuroscience, concerned with the way neurons and neuronal systems process and transmit information. However, the term “code” has been mostly used as a metaphor, seldom acknowledging the formal definitions introduced by information theory, and the contributions of linguistics and semiotics not at all. The heuristic potential of the latter was suggested by structuralism, which turned the methods and findings of linguistics to other fields of knowledge. For the study of complex communication systems, such as human language and music, the necessity of an approach that considers multilayered, nested, structured organization of symbols becomes evident. We work under the hypothesis that the neural code might be as complex as these human-made codes. To test this, we propose a bottom-up approach, constructing a symbolic logic in order to translate neuronal signals into music scores.MethodsWe recorded single cells’ activity from the rat’s globus pallidus pars interna under conditions of full alertness, blindfoldedness and environmental silence. We analyzed the signals with statistical, spectral, and complex methods, including Fast Fourier Transform, Hurst exponent and recurrence plot analysis.ResultsThe results indicated complex behavior and recurrence graphs consistent with fractality, and a Hurst exponent &gt;0.5, evidencing temporal persistence. On the whole, these features point toward a complex behavior of the time series analyzed, also present in classical music, which upholds the hypothesis of structural similarities between music and neuronal activity. Furthermore, through our experiment we performed a comparison between music and raw neuronal activity. Our results point to the same conclusion, showing the structures of music and neuronal activity to be homologous. The scores were not only spontaneously tonal, but they exhibited structure and features normally present in human-made musical creations.DiscussionThe hypothesis of a structural homology between the neural code and the code of music holds, suggesting that some of the insights introduced by linguistic and semiotic theory might be a useful methodological resource to go beyond the limits set by metaphoric notions of “code.”
Association of eating habits with health perception and diseases among Chinese physicians: a cross-sectional study
Authors: Chen Moxi , Xu Xuan , Liu Yinghua , Yao Ying , Zhang Pianhong , Liu Jingfang , Zhang Qian , Li Rongrong , Li Hailong , Liu Yan , Chen Wei 
Published: August 2023

BackgroundSome eating habits may be related to the development of gastrointestinal diseases, obesity, and related metabolic dysfunctions. Because of long working hours, and shift schedules, physicians are more likely to form such eating habits and have a high risk of developing these diseases.ObjectivesWe aimed to investigate the association between physicians’ eating habits and their health perception and diseases.MethodsBetween 24 June and 5 August 2020, we performed convenience sampling of in-service physicians in hospitals in mainland China. A questionnaire was administered to collect data pertaining to basic sociodemographic characteristics, eating habits, health-related information such as body mass index classification, and prevalence of common diseases. The associations among eating habits and perceived suboptimal health status, micronutrient deficiency-related diseases, obesity, and related metabolic diseases were analysed.ResultsThe prevalence of unhealthy eating habits was high: more eating out-of-home (53.4% in hospital canteens, 23.0% in restaurants and takeaways), fewer meals at home, irregular meals (30.5%), and eating too fast (the duration &lt;10 min, 34.6%). Among those with the above eating habits, the prevalence rates of sub-optimal health and disease were higher than among those without the above eating habits.ConclusionEating habits such as frequent eating out-of-home, irregular meals, and eating too fast were common among physicians, and were significantly related to perceived sub-optimal health status and disease occurrence.
Exploring the potentials of sorghum genotypes: a comprehensive study on nutritional qualities, functional metabolites, and antioxidant capacities
Authors: Lee Sukyeung , Choi Yu-Mi , Shin Myoung-Jae , Yoon Hyemyeong , Wang Xiaohan , Lee Yoonjung , Yi Jungyoon , Jeon Young-ah , Desta Kebede Taye 
Published: August 2023

IntroductionSorghum, long regarded as one of the most underutilized crops, has received attention in recent years. As a result, conducting multidisciplinary studies on the potential and health benefits of sorghum resources is vital if they are to be fully exploited. In this study, the nutritional contents, functional metabolites, and antioxidant capacities of 23 sorghum breeding lines and three popular cultivars were assessed.Materials and methodAll of the sorghum genotypes were grown under the same conditions, and mature seeds were hand-harvested. The metabolite contents and antioxidant capacities of sorghum seeds were assessed using standard protocols. Fatty acids were quantified using a gas chromatography-flame ionization detector, whereas flavonoids and 3-deoxyanthocyanidins were analyzed using a liquid chromatography-tandem mass spectrometry method. The data were analyzed using both univariate and multivariate statistical approaches.Results and discussionTotal protein (9.05–14.61%), total fat (2.99–6.91%), crude fiber (0.71–2.62%), dietary fiber (6.72–16.27%), total phenolic (0.92–10.38 mg GAE/g), and total tannin (0.68–434.22 mg CE/g) contents varied significantly across the sorghum genotypes (p &lt; 0.05). Antioxidant capacity, measured using three assays, also differed significantly. Five fatty acids, including palmitic, stearic, oleic, linoleic, and linolenic acids, were found in all the sorghum genotypes with statistically different contents (p &lt; 0.05). Furthermore, the majority of the sorghum genotypes contained four 3-deoxyanthocyanidins, including luteolinidin, apigeninidin, 5-methoxyluteolinidin, and 7-methoxyapigeninidin, as well as two dominant flavonoids, luteolin and apigenin. Compared to the cultivars, some breeding lines had significantly high levels of metabolites and antioxidant activities. On the other hand, statistical analysis showed that total tannin, total phenolic, and antioxidant capacities varied significantly across white, yellow, and orange genotypes. Principal component analysis was used to differentiate the sorghum genotypes based on seed color and antioxidant index levels. Pearson’s correlation analysis revealed strong links between biosynthetically related metabolites and those with synergistic antioxidant properties.ConclusionThis research demonstrated the diversity of the sorghum resources investigated. Those genotypes with high levels of nutritional components, functional metabolites, and antioxidant activities could be used for consumption and breeding programs.
Eph receptor B6 shapes a cold immune microenvironment, inhibiting anti-cancer immunity and immunotherapy response in bladder cancer
Authors: Jia Xiaolong , Zhang Dongxu , Zhou Cheng , Yan Zejun , Jiang Zhaohui , Xie Liping , Jiang Junhui 
Published: August 2023

BackgroundThe role of Eph receptors and related ephrin (EFN) ligands (as the largest family of transmembrane-bound RTKs) in immunomodulation in many types of cancer, especially bladder cancer (BLCA), is scarcely known.MethodsA pan-cancer dataset was retrieved from The Cancer Genome Atlas (TCGA) to explore the relation between Eph receptor/EFN ligand family genes and immunomodulators and tumor-infiltrated immune cells (TIICs). Local BLCA, GSE32894, and GSE31684 cohorts were applied to validate. The IMvigor210 cohort was employed to explore the relationship between EPHB6 and immunotherapy response. Moreover, association between EPHB6 and molecular subtype was investigated to explore potential therapeutic strategies. Immunohistochemical staining of CD8 and CD68 was performed to validate the correlation between EPHB6 and TIICs.ResultsThe pan-cancer analysis revealed variations in the immunological effects of Eph receptor/EFN ligand family genes across different types of cancer. EPHB6 expression negatively correlated with the expression of the majority of immunomodulators (including HLA and immune checkpoints), and CD8 T cells and macrophages in both the TCGA-BLCA and validation BLCA cohorts, shaping a cold immune microenvironment with inhibited immunity. In the IMvigor210 cohort, patients with high-EPHB6 highly correlated with a non-inflamed, low PD-L1 expression immune phenotype, and correspondingly, with less responders to immunotherapy. The high-EPHB6 group, enriched with the basal subtype, presented significantly fewer TP53 and more FGFR3 genomic alterations. Finally, a novel EPHB6-related Genes signature, with reliable and robust ability in prognosis prediction, was constructed.ConclusionsThis study comprehensively investigated the immunological effects of Eph receptor/EFN ligand family genes pan-cancer, and specially identified the immunosuppressive role of EPHB6 in BLCA. Furthermore, EPHB6 may predict the molecular subtype and prognosis of BLCA, and serve as a novel therapeutic target to improve the sensitivity of immunotherapy.
Dual-energy CT-based radiomics for predicting invasiveness of lung adenocarcinoma appearing as ground-glass nodules
Authors: Zheng Yuting , Han Xiaoyu , Jia Xi , Ding Chengyu , Zhang Kailu , Li Hanting , Cao Xuexiang , Zhang Xiaohui , Zhang Xin , Shi Heshui 
Published: August 2023

ObjectivesTo explore the value of radiomics based on Dual-energy CT (DECT) for discriminating preinvasive or MIA from IA appearing as GGNs before surgery.MethodsThe retrospective study included 92 patients with lung adenocarcinoma comprising 30 IA and 62 preinvasive-MIA, which were further divided into a training (n=64) and a test set (n=28). Clinical and radiographic features along with quantitative parameters were recorded. Radiomics features were derived from virtual monoenergetic images (VMI), including 50kev and 150kev images. Intraclass correlation coefficients (ICCs), Pearson’s correlation analysis and least absolute shrinkage and selection operator (LASSO) penalized logistic regression were conducted to eliminate unstable and redundant features. The performance of the models was evaluated by area under the curve (AUC) and the clinical utility was assessed using decision curve analysis (DCA).ResultsThe DECT-based radiomics model performed well with an AUC of 0.957 and 0.865 in the training and test set. The clinical-DECT model, comprising sex, age, tumor size, density, smoking, alcohol, effective atomic number, and normalized iodine concentration, had an AUC of 0.929 in the training and 0.719 in the test set. In addition, the radiomics model revealed a higher AUC value and a greater net benefit to patients than the clinical-DECT model.ConclusionDECT-based radiomics features were valuable in predicting the invasiveness of GGNs, yielding a better predictive performance than the clinical-DECT model.
Radiographic response to neoadjuvant therapy in pleural mesothelioma should serve as a guide for patient selection for cytoreductive operations
Authors: Deboever Nathaniel , Zhou Nicolas , McGrail Daniel J. , Tomczak Katarzyna , Oliva Jacqueline L. , Feldman Hope A. , Parra Edwin , Zhang Jianjun , Lee Percy P. , Antonoff Mara B. , Hofstetter Wayne L. , Mehran Reza J. , Rajaram Ravi , Rice David C. , Roth Jack A. , Swisher Stephen S. , Vaporciyan Ara A. , Altan Mehmet , Weissferdt Annikka , Tsao Anne S. , Haymaker Cara L. , Sepesi Boris 
Published: August 2023

BackgroundMalignant pleural mesothelioma (MPM) is associated with poor prognosis despite advances in multimodal therapeutic strategies. While patients with resectable disease may benefit from added survival with oncologic resection, patient selection for mesothelioma operations often relies on both objective and subjective evaluation metrics. We sought to evaluate factors associated with improved overall survival (OS) in patients with mesothelioma who underwent macroscopic complete resection (MCR).MethodsPatients with MPM who received neoadjuvant therapy and underwent MCR were identified in a prospectively maintained departmental database. Clinicopathologic, blood-based, and radiographic variables were collected and included in a Cox regression analysis (CRA). Response to neoadjuvant therapy was characterized by a change in tumor thickness from pretherapy to preoperative scans using the modified RECIST criteria.ResultsIn this study, 99 patients met the inclusion criteria. The median age of the included patients was 64.7 years, who were predominantly men, had smoking and asbestos exposure, and who received neoadjuvant therapy. The median change in tumor thickness following neoadjuvant therapy was –16.5% (interquartile range of -49.7% to +14.2%). CRA demonstrated reduced OS associated with non-epithelioid histology [hazard ratio (HR): 3.06, 95% confidence interval (CI): 1.62–5.78, p &lt; 0.001] and a response to neoadjuvant therapy inferior to the median (HR: 2.70, CI: 1.55–4.72, p &lt; 0.001). Patients who responded poorly (below median) to neoadjuvant therapy had lower median survival (15.8 months compared to 38.2 months, p &lt; 0.001).ConclusionPoor response to neoadjuvant therapy in patients with MPM is associated with poor outcomes even following maximum surgical cytoreduction and should warrant a patient-centered discussion regarding goals of care and may therefore help guide further therapeutic decisions.
β-hydroxybutyrate impairs bovine oocyte maturation via pyruvate dehydrogenase (PDH) associated energy metabolism abnormality
Authors: Zhang Kai-Yan , Guo Jing , Zhan Cheng-Lin , Yuan Chong-Shan , Min Chang-Guo , Li Zhi-Qiang , Liu Hong-Yu , Wang Jun , Zhao Jing , Lu Wen-Fa , Ma Xin 
Published: August 2023

Background: Ketosis is one of the most frequent and costly metabolic disorders in high-producing dairy cows, and negatively associated with the health and reproductive performance of bovine. Ketosis is mainly caused by the accumulation of ketone body β-hydroxybutyric acid and its diagnosis is based on β-hydroxybutyrate (βHB) concentration in blood.Methods: In this study, we investigated the effects of βHB on bovine oocyte maturation in the concentration of subclinical (1.2 mM) βHB and clinical (3.6 mM).Results: The results showed βHB disrupted bovine oocyte maturation and development capacity. Further analysis showed that βHB induced oxidative stress and mitochondrial dysfunction, as indicated by the increased level of reactive oxygen species (ROS), disrupted mitochondrial structure and distribution, and depolarized membrane potential. Furthermore, oxidative stress triggered early apoptosis, as shown by the enhanced levels of Caspase-3 and Annexin-V. Moreover, 3.6 mM βHB induced the disruption of the pyruvate dehydrogenase (PDH) activity, showing with the decrease of the global acetylation modification and the increase of the abnormal spindle rate.Conclusion: Our study showed that βHB in subclinical/clinical concentration had toxic effects on mitochondrial function and PDH activity, which might affect energy metabolism and epigenetic modification of bovine oocytes and embryos.