Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolic management of microenvironment acidity in glioblastoma

Glioblastoma (GBM), similar to most cancers, is dependent on fermentation metabolism for the synthesis of biomass and energy (ATP) regardless of the cellular or genetic heterogeneity seen within the tumor. The transition from respiration to fermentation arises from the documented defects in the number, the structure, and the function of mitochondria and mitochondrial-associated membranes in GBM tissue. Glucose and glutamine are the major fermentable fuels that drive GBM growth. The major waste products of GBM cell fermentation (lactic acid, glutamic acid, and succinic acid) will acidify the microenvironment and are largely responsible for drug resistance, enhanced invasion, immunosuppression, and metastasis. Besides surgical debulking, therapies used for GBM management (radiation, chemotherapy, and steroids) enhance microenvironment acidification and, although often providing a time-limited disease control, will thus favor tumor recurrence and complications. The simultaneous restriction of glucose and glutamine, while elevating non-fermentable, anti-inflammatory ketone bodies, can help restore the pH balance of the microenvironment while, at the same time, providing a non-toxic therapeutic strategy for killing most of the neoplastic cells.
Identification of immune-related ferroptosis prognostic marker and in-depth bioinformatics exploration of multi-omics mechanisms in thyroid cancer

Background: Factors such as variations in thyroid carcinoma (THCA) gene characteristics could influence the clinical outcome. Ferroptosis and immunity have been verified to play an essential role in various cancers, and could affect the cancer patients’ prognosis. However, their relationship to the progression and prognosis of many types of THCA remains unclear. Methods: First, we extracted prognosis-related immune-related genes and ferroptosis-related genes from 2 databases for co-expression analysis to obtain prognosis-related differentially expressed immune-related ferroptosis genes (PR-DE-IRFeGs), and screened BID and CDKN2A for building a prognostic model. Subsequently, multiple validation methods were used to test the model’s performance and compare its performance with other 4 external models. Then, we explored the mechanism of immunity and ferroptosis in the occurrence, development and prognosis of THCA from the perspectives of anti-tumor immunity, CDKN2A-related competitive endogenous RNA regulatory, copy number variations and high frequency gene mutation. Finally, we evaluated this model’s clinical practice value. Results: BID and CDKN2A were identified as prognostic risk and protective factors, respectively. External data and qRT-PCR experiment also validated their differential expression. The model’s excellent performance has been repeatedly verified and outperformed other models. Risk scores were significantly associated with most immune cells/functions. Risk score/2 PR-DE-IRFeGs expression was strongly associated with BRAF/NRAS/HRAS mutation. Single copy number deletion of CDKN2A is associated with upregulation of CDKN2A expression and worse prognosis. The predicted regulatory network consisting of CYTOR, hsa-miRNA-873-5p and CDKN2A was shown to significantly affect prognosis. The model and corresponding nomogram have been shown to have excellent clinical practice value. Conclusion: The model can effectively predict the THCA patients’ prognosis and guide clinical treatment. Ferroptosis and immunity may be involved in the THCA’s progression through antitumor immunity and BRAF/NRAS/HRAS mutation. CYTOR-hsa-miRNA-873-5p-CDKN2A regulatory networks and single copy number deletion of CDKN2A may also affect THCA′ progression and prognosis.
ACO1 and IREB2 downregulation confer poor prognosis and correlate with autophagy-related ferroptosis and immune infiltration in KIRC

Background ACO1 and IREB2 are two homologous cytosolic regulatory proteins, which sense iron levels and change iron metabolism–linked molecules. These two genes were noticeably decreased in kidney renal clear cell carcinoma (KIRC), which confer poor survival. Meanwhile, there is a paucity of information about the mechanisms and clinical significance of ACO1 and IREB2 downregulation in renal cancers. Methods The expression profiles of ACO1 and IREB2 were assessed using multiple public data sets via several bioinformatics platforms. Clinical and pathological information was utilized to stratify cohorts for comparison. Patient survival outcomes were evaluated using the Kaplan–Meier plotter, a meta-analysis tool. The correlations of ACO1 and IREB2 with ferroptosis were further evaluated in The Cancer Genome Atlas (TCGA)–KIRC database. Tumor immune infiltration was analyzed using the CIBERSORT, TIMER, and GEPIA data resources. ACO1 antagonist sodium oxalomalate (OMA) and IREB2 inhibitor sodium nitroprusside (SNP) was used to treat renal cancer ACHN cells together with sorafenib. Results KIRC patients with low ACO1 or IREB2 contents exhibited a remarkably worse survival rate in contrast with those with high expression in Kaplan–Meier survival analyses. Meanwhile, ACO1 and IREB2 regulate autophagy-linked ferroptosis along with immune cell invasion in the tumor microenvironment in KIRC patients. Blocking the activation of these two genes by their inhibitors OMA and SNP ameliorated sorafenib-triggered cell death, supporting that ACO1 and IREB2 could be participated in its cytotoxic influence on renal cancer cells. Conclusion ACO1 and IREB2 downregulation in renal cancers were correlated with cancer aggressiveness, cellular iron homeostasis, cytotoxic immune cell infiltration, and patient survival outcomes. Our research is integral to verify the possible significance of ACO1 and IREB2 contents as a powerful signature for targeted treatment or novel immunotherapy in clinical settings.
Motivation for MOOC learning persistence: An expectancy–value theory perspective

Managing learning continuity is critical for successful MOOC learning. Thus, enabling learners to have learning persistence needs to be integrated into the MOOC learning design. Motivation effort is a critical component enabling students to maintain continuous MOOC learning. The expectancy–value theory explains why learners engage in learning: (1) they have a higher perceived ability for learning success, (2) place value on learning, and (3) avoid psychological costs. However, it is unclear how these factors affect MOOC learning persistence and how learners’ motivation is formed from this perspective. This experimental study explored how learners’ motivational variables affect their learning persistence, focusing on the expectancy–value theory. The results of this study indicated that academic self-efficacy and task value had significant positive effects on learning persistence. The structural relationship of antecedent, process, and outcome variables showed that teaching presence as an antecedent had a significantly positive effect on academic self-efficacy and task value. Among the three factors of the expectancy–value theory, only the task value influenced learning persistence through student engagement as a mediator. Based on the results, suggestions are provided for motivating MOOC environments that support learners’ continuous MOOC learning.
Biophysical characterisation of the Bcl-x pre-mRNA and binding specificity of the ellipticine derivative GQC-05: Implication for alternative splicing regulation

The BCL2L1 gene expresses two isoforms of Bcl-x protein via the use of either of two alternative 5′ splice sites (5′ss) in exon 2. These proteins have antagonistic actions, Bcl-XL being anti-apoptotic and Bcl-XS pro-apoptotic. In a number of cancers the Bcl-XL isoform is over-expressed, resulting in cancer cell survival and growth, so switching splicing to the Xs isoform could have therapeutic benefits. We have previously proposed that a putative G-quadruplex (G4) exists downstream of the XS 5′ss and shown that the ellipticine derivative GQC-05, a previously identified DNA G4-specific ligand, induces an increase in the XS/XL ratio both in vitro and in cells. Here, we demonstrate that this G4 forms in vitro and that the structure is stabilised in the presence of GQC-05. We also show that GQC-05 binds RNA non-specifically in buffer conditions, but selectively to the Bcl-x G4 in the presence of nuclear extract, highlighting the limitations of biophysical measurements taken outside of a functional environment. We also demonstrate that GQC-05 is able to shift the equilibrium between competing G4 and duplex structures towards the G4 conformation, leading to an increase in accessibility of the XS 5′ss, supporting our previous model on the mechanism of action of GQC-05.
Continuous theta burst stimulation over left supplementary motor area facilitates auditory-vocal integration in individuals with Parkinson’s disease

Accumulating evidence suggests that impairment in auditory-vocal integration characterized by abnormally enhanced vocal compensations for auditory feedback perturbations contributes to hypokinetic dysarthria in Parkinson’s disease (PD). However, treatment of this abnormality remains a challenge. The present study examined whether abnormalities in auditory-motor integration for vocal pitch regulation in PD can be modulated by neuronavigated continuous theta burst stimulation (c-TBS) over the left supplementary motor area (SMA). After receiving active or sham c-TBS over left SMA, 16 individuals with PD vocalized vowel sounds while hearing their own voice unexpectedly pitch-shifted two semitones upward or downward. A group of pairwise-matched healthy participants was recruited as controls. Their vocal responses and event-related potentials (ERPs) were measured and compared across the conditions. The results showed that applying c-TBS over left SMA led to smaller vocal responses paralleled by smaller P1 and P2 responses and larger N1 responses in individuals with PD. Major neural generators of reduced P2 responses were located in the right inferior and medial frontal gyrus, pre- and post-central gyrus, and insula. Moreover, suppressed vocal compensations were predicted by reduced P2 amplitudes and enhanced N1 amplitudes. Notably, abnormally enhanced vocal and P2 responses in individuals with PD were normalized by c-TBS over left SMA when compared to healthy controls. Our results provide the first causal evidence that abnormalities in auditory-motor control of vocal pitch production in PD can be modulated by c-TBS over left SMA, suggesting that it may be a promising non-invasive treatment for speech motor disorders in PD.
Sacubitril-valsartan for the treatment of hypertension in China: A cost-utility analysis based on meta-analysis of randomized controlled trials

Background Sacubitril-valsartan was recommended for heart failure (HF) and proven cost-effective in HF. Recently, sacubitril-valsartan has been recommended to treat hypertension by the Chinese expert consensus. The cost utility of sacubitril-valsartan for hypertension remains uninvestigated. Methods A meta-analysis of randomized controlled trials (RCTs) was performed to investigate the real efficacy of sacubitril-valsartan on blood pressure, compared with angiotensin receptor blockers or placebo. A lifetime Markov model was developed to compare the cost utility of sacubitril-valsartan vs. valsartan. The primary outcome was the incremental cost-utility ratio (ICUR), representing the ratio of incremental costs to the incremental utility. The willingness-to-pay (WTP) threshold was three times of per capita gross domestic product (GDP) in China in 2021. Sacubitril-valsartan was considered cost-effective if the ICUR obtained was lower than the WTP threshold, otherwise, sacubitril-valsartanis was not cost-effective. Results A total of 10 RCTs of 5,781 patients were included in the meta-analysis. For comparison of sacubitril-valsartan 400 mg/day vs. valsartan 320 mg/day, a reduction in blood pressure (BP) of −5.97 (−6.38, −5.56) (p < 0.01) was observed. Cost-utility analysis showed that for a 60-year-old patient with hypertension, if sacubitril-valsartan was prescribed as the antihypertensive agent, he had a life expectancy of 11.91 quality-adjusted life-years (QALYs) with costs of 65,066 CNY, and if valsartan was prescribed as the antihypertensive agent, the life expectancy would be 11.82 QALY with costs of 54,769 CNY; thus, an ICUR of 108,622 CNY/QALY was obtained, lower than the WTP threshold. Conclusion Compared with valsartan, sacubitril-valsartan is more effective in reducing blood pressure and may result in more quality-adjusted life-year, although with higher costs. Sacubitril-valsartan is cost-effective for hypertension in the current China setting under the willingness-to-pay threshold of 3 times of per capita GDP.
Remote evaluation of augmented reality interaction with personal health information

This article discusses novel research methods used to examine how Augmented Reality (AR) can be utilized to present “omic” (i.e., genomes, microbiomes, pathogens, allergens) information to non-expert users. While existing research shows the potential of AR as a tool for personal health, methodological challenges pose a barrier to the ways in which AR research can be conducted. There is a growing need for new evaluation methods for AR systems, especially as remote testing becomes increasingly popular. In this article, we present two AR studies adapted for remote research environments in the context of personal health. The first study (n = 355) is a non-moderated remote study conducted using an AR web application to explore the effect of layering abstracted pathogens and mitigative behaviors on a user, on perceived risk perceptions, negative affect, and behavioral intentions. This study introduces methods that address participant precursor requirements, diversity of platforms for delivering the AR intervention, unsupervised setups, and verification of participation as instructed. The second study (n = 9) presents the design and moderated remote evaluation of a technology probe, a prototype of a novel AR tool that overlays simulated timely and actionable environmental omic data in participants' living environment, which helps users to contextualize and make sense of the data. Overall, the two studies contribute to the understanding of investigating AR as a tool for health behavior and interventions for remote, at-home, empirical studies.
From descriptive connectome to mechanistic connectome: Generative modeling in functional magnetic resonance imaging analysis

As a newly emerging field, connectomics has greatly advanced our understanding of the wiring diagram and organizational features of the human brain. Generative modeling-based connectome analysis, in particular, plays a vital role in deciphering the neural mechanisms of cognitive functions in health and dysfunction in diseases. Here we review the foundation and development of major generative modeling approaches for functional magnetic resonance imaging (fMRI) and survey their applications to cognitive or clinical neuroscience problems. We argue that conventional structural and functional connectivity (FC) analysis alone is not sufficient to reveal the complex circuit interactions underlying observed neuroimaging data and should be supplemented with generative modeling-based effective connectivity and simulation, a fruitful practice that we term “mechanistic connectome. ” The transformation from descriptive connectome to mechanistic connectome will open up promising avenues to gain mechanistic insights into the delicate operating principles of the human brain and their potential impairments in diseases, which facilitates the development of effective personalized treatments to curb neurological and psychiatric disorders.
Association of body composition with pubertal timing in children and adolescents from Guangzhou, China

Objective An ongoing debate surrounds the relationship between body composition and pubertal timing, in particular for boys. This cross-sectional study aimed to investigate the association of body composition with pubertal timing among children and adolescents. Methods A total of 1,493 boys and 1,261 girls who entered puberty were enrolled in Guangzhou, China. Tanner stages were evaluated by examination of breast development for girls and testicular volume for boys. Fat mass (FM) and fat-free mass (FFM) were determined by bioelectrical impedance analysis. Parameters for body composition were transformed into age-and gender-specific Z-scores. The association of body composition with pubertal timing was examined using multinomial logistic regression with inverse probability weighting (IPW) based on the propensity score. Results For boys, IPW analysis showed Z-scores of body fat percentage (BF%) and FM index (FMI) were negatively associated with early puberty (OR = 0.75, 95% CI = 0.64–0.87; OR = 0.74, 95% CI = 0.63–0.88). As for girls, in contrast to boys, positive associations were seen between BF% and FMI with early puberty (OR = 1.39, 95% CI = 1.19–1.64; OR = 1.59, 95% CI = 1.33–1.90). With respect to appendicular skeletal muscle mass index (ASMI), there was a positive association with early puberty and a negative one with late puberty in boys (OR = 1.26, 95% CI = 1.07–1.49; OR = 0.82, 95% CI = 0.69–0.99). Conclusion There is a positive association of FM with early puberty for girls while negative for boys. FFM yields a positive association with early puberty and a negative one with late puberty in boys, but not in girls. Our findings highlight the gender differences in the connection between body composition and pubertal onset.
Transportation and Land Property Rights: Economic Impacts on Agricultural Productivity

This paper empirically investigates the relationship between the effectiveness of land property rights and the impacts of transportation on agricultural output. It is assumed that property rights are a pre-condition for the functioning of land markets. The hypothesis is that if land markets are functional then the impacts of transportation are higher because farmers can respond to improvements in transportation either by making productivity-enhancing investments or by engaging in efficient land transactions. An agricultural production function was estimated where both transportation and property rights were treated as constituents of total factor productivity, using panel data from 76 countries from 2007 to 2013. Ordinary least squares and two-stage least squares regressions revealed that, contrary to our expectations, the impacts of transportation are higher in countries with less effective property rights systems. Three possible explanations are raised. First, it is possible that better property rights are correlated with higher government intervention in agriculture, which negatively impacts productivity. Second, possibly larger benefits from improvements in property rights are to be made in the earlier stages of development. Third, it is possible that high productivity is associated with large farms because of economies of scale. Since they are more likely to be found in land-rich countries, which tend to have less effective property rights, the present paper raises concerns that land transactions triggered by transportation projects may lead to outcomes that are not Pareto-optimal, with possible consequences for social indicators such as rural poverty.
Does health literacy promote COVID-19 awareness? Evidence from Zhejiang, China

Background Health literacy (HL) is considered a crucial determinant of disease prevention and control. However, the role of HL in the Coronavirus Disease 2019 (COVID-19) pandemic has not been studied using provincial representative data among Chinese residents. This study aimed to assess the association between HL and COVID-19 awareness among Zhejiang residents based on the 2020 China Health Literacy Survey (CHLS). Methods The study was conducted among 5,596 residents aged 15–69 in Zhejiang using multistage, stratified, and probability proportional to size sampling. COVID-19 awareness and HL were assessed using the “Chinese Citizen Health Literacy Questionnaire (2020)” in Zhejiang. The covariates were divided into predisposing factors, enabling factors, and need factors according to Anderson's model. Data were analyzed by the chi-square test and logistic regression. Results The study showed that HL and COVID-19 awareness levels of residents were 24.84% and 8.06%, respectively, in Zhejiang in 2020. After adjusting for covariates, residents with adequate HL were more likely to have better COVID-19 awareness (odds ratio [OR] = 5.22, 95% CI = 4.13–6.59, p < 0.001). Three dimensions of HL (knowledge and attitudes, behavior and lifestyle, and health-related skills) were associated with COVID-19 awareness. Additionally, COVID-19 awareness was associated with age, occupation, family size, annual household income, and chronic conditions. Conclusion COVID-19 awareness is significantly associated with HL, suggesting that promoting HL is an important component of health education, disease prevention, and health promotion in response to the COVID-19 pandemic and even possible public health emergencies in the future.
Targeted re-sequencing on 1p22 among non-syndromic orofacial clefts from Han Chinese population

Rs560426 at 1p22 was proved to be associated with NSCL/P (non-syndromic cleft lip with or without the palate) in several populations, including Han Chinese population. Here, we conducted a deep sequencing around rs560426 to locate more susceptibility variants in this region. In total, 2,293 NSCL/P cases and 3,235 normal controls were recruited. After sequencing, association analysis was performed. Western blot, RT-qPCR, HE, immunofluorescence staining, and RNA sequencing were conducted for functional analyses of the selected variants. Association analysis indicated that rs77179923 was the only SNP associated with NSCLP specifically (p = 4.70E-04, OR = 1.84), and rs12071152 was uniquely associated with LCLO (p = 4.00E-04, OR = 1.30, 95%CI: 1.12–1.51). Moreover, de novo harmful rare variant NM_004815. 3, NP_004806. 3; c.1652G>C, p.R551T in ARHGAP29 resulted in a decreased expression level of ARHGAP29, which in turn affected NSCL/P-related biological processes; however, no overt cleft palate (CP) phenotype was observed. In conclusion, rs12071152 was a new susceptible variant, which is specifically associated with LCLO among the Han Chinese population. Allele A of it could increase the risk of having a cleft baby. Rs77179923 and rare variant NM_004815. 3, NP_004806. 3; c.1652G>C, p.R551T at 1p22 were both associated with NSCLP among the Han Chinese population. However, this missense variation contributes to no overt CP phenotype due to dosage insufficiency or compensation from other genes.