Miracle-dz/UniFAR-FTUs huggingface dataset:
A Computational Framework for Studying Gut-Brain Axis in Autism Spectrum Disorder

Introduction The integrity of the intestinal epithelium is crucial for human health and is harmed in autism spectrum disorder (ASD). An aberrant gut microbial composition resulting in gut-derived metabolic toxins was found to damage the intestinal epithelium, jeopardizing tissue integrity. These toxins further reach the brain via the gut-brain axis, disrupting the normal function of the brain. A mechanistic understanding of metabolic disturbances in the brain and gut is essential to design effective therapeutics and early intervention to block disease progression. Herein, we present a novel computational framework integrating constraint based tissue specific metabolic (CBM) model and whole-body physiological pharmacokinetics (PBPK) modeling for ASD. Furthermore, the role of gut microbiota, diet, and oxidative stress is analyzed in ASD. Methods A representative gut model capturing host-bacteria and bacteria-bacteria interaction was developed using CBM techniques and patient data. Simultaneously, a PBPK model of toxin metabolism was assembled, incorporating multi-scale metabolic information. Furthermore, dynamic flux balance analysis was performed to integrate CBM and PBPK. The effectiveness of a probiotic and dietary intervention to improve autism symptoms was tested on the integrated model. Results The model accurately highlighted critical metabolic pathways of the gut and brain that are associated with ASD. These include central carbon, nucleotide, and vitamin metabolism in the host gut, and mitochondrial energy and amino acid metabolisms in the brain. The proposed dietary intervention revealed that a high-fiber diet is more effective than a western diet in reducing toxins produced inside the gut. The addition of probiotic bacteria Lactobacillus acidophilus, Bifidobacterium longum longum, Akkermansia muciniphila, and Prevotella ruminicola to the diet restores gut microbiota balance, thereby lowering oxidative stress in the gut and brain. Conclusion The proposed computational framework is novel in its applicability, as demonstrated by the determination of the whole-body distribution of ROS toxins and metabolic association in ASD. In addition, it emphasized the potential for developing novel therapeutic strategies to alleviate autism symptoms. Notably, the presented integrated model validates the importance of combining PBPK modeling with COBRA -specific tissue details for understanding disease pathogenesis.
Clinical Significance and Potential Mechanisms of ATP Binding Cassette Subfamily C Genes in Hepatocellular Carcinoma

The purpose of this investigation was to assess the diagnostic and prognostic significance of ATP binding cassette subfamily C (ABCC) genes in hepatocellular carcinoma (HCC). The Student t-test was used to compare the expression level of ABCCs between HCC and paraneoplastic tissues. Receiver operating characteristic curve (ROC) analysis was applied for diagnostic efficiency assessment. The Kaplan–Meier method and Cox proportional hazards model were respectively applied for survival analysis. Genes with prognostic significance were subsequently used to construct prognostic models. From the perspective of genome-wide enrichment analysis, the mechanisms of prognosis-related ABCC genes were attempted to be elaborated by gene set enrichment analysis (GSEA). It was observed in the TCGA database that ABCC1, ABCC4, ABCC5, and ABCC10 were significantly upregulated in tumor tissues, while ABCC6 and ABCC7 were downregulated in HCC tissues. Receiver operating characteristic analysis revealed that ABCC7 might be a potential diagnostic biomarker in HCC. ABCC1, ABCC4, ABCC5, and ABCC6 were significantly related to the prognosis of HCC in the TCGA database. The prognostic significance of ABCC1, ABCC4, ABCC5, and ABCC6 was also observed in the Guangxi cohort. In the Guangxi cohort, both polymerase chain reaction and IHC (immunohistochemical) assays demonstrated higher expression of ABCC1, ABCC4, and ABCC5 in HCC compared to liver tissues, while the opposite was true for ABCC6. GSEA analysis indicated that ABCC1 was associated with tumor differentiation, nod-like receptor signal pathway, and so forth. It also revealed that ABCC4 might play a role in HCC by regulating epithelial-mesenchymal transition, cytidine analog pathway, met pathway, and so forth. ABCC5 might be associated with the fatty acid metabolism and KRT19 in HCC. ABCC6 might impact the cell cycle in HCC by regulating E2F1 and myc. The relationship between ABCC genes and immune infiltration was explored, and ABCC1,4,5 were found to be positively associated with infiltration of multiple immune cells, while ABCC6 was found to be the opposite. In conclusion, ABCC1, ABCC4, ABCC5, and ABCC6 might be prognostic biomarkers in HCC. The prognostic models constructed with ABCC1, ABCC4, ABCC5, and ABCC6 had satisfactory efficacy.
Epigenetic and Transcriptional Control of Erythropoiesis

Erythropoiesis is a process of enormous magnitude, with the average person generating two to three million red cells every second. Erythroid progenitors start as large cells with large nuclei, and over the course of three to four cell divisions they undergo a dramatic decrease in cell size accompanied by profound nuclear condensation, which culminates in enucleation. As maturing erythroblasts are undergoing these dramatic phenotypic changes, they accumulate hemoglobin and express high levels of other erythroid-specific genes, while silencing much of the non-erythroid transcriptome. These phenotypic and gene expression changes are associated with distinct changes in the chromatin landscape, and require close coordination between transcription factors and epigenetic regulators, as well as precise regulation of RNA polymerase II activity. Disruption of these processes are associated with inherited anemias and myelodysplastic syndromes. Here, we review the epigenetic mechanisms that govern terminal erythroid maturation, and their role in human disease.
miRNAs as Predictive Factors in Early Diagnosis of Gestational Diabetes Mellitus

Introduction Circulating miRNAs are important mediators in epigenetic changes. These non-coding molecules regulate post-transcriptional gene expression by binding to mRNA. As a result, they influence the development of many diseases, such as gestational diabetes mellitus (GDM). Therefore, this study investigates the changes in the miRNA profile in GDM patients before hyperglycemia appears. Materials and Methods The study group consisted of 24 patients with GDM, and the control group was 24 normoglycemic pregnant women who were matched for body mass index (BMI), age, and gestational age. GDM was diagnosed with an oral glucose tolerance test between the 24th and 26th weeks of pregnancy. The study had a prospective design, and serum for analysis was obtained in the first trimester of pregnancy. Circulating miRNAs were measured using the NanoString quantitative assay platform. Validation with real time-polymerase chain reaction (RT-PCR) was performed on the same group of patients. Mann-Whitney U-test and Spearman correlation were done to assess the significance of the results. Results Among the 800 miRNAs, 221 miRNAs were not detected, and 439 were close to background noise. The remaining miRNAs were carefully investigated for their average counts, fold changes, p-values, and false discovery rate (FDR) scores. We selected four miRNAs for further validation: miR-16-5p, miR-142-3p, miR-144-3p, and miR-320e, which showed the most prominent changes between the studied groups. The validation showed up-regulation of miR-16-5p (p<0.0001), miR-142-3p (p=0.001), and miR-144-3p (p=0.003). Conclusion We present changes in miRNA profile in the serum of GDM women, which may indicate significance in the pathophysiology of GDM. These findings emphasize the role of miRNAs as a predictive factor that could potentially be useful in early diagnosis.
A Cross-Corpus Speech-Based Analysis of Escalating Negative Interactions

The monitoring of an escalating negative interaction has several benefits, particularly in security, (mental) health, and group management. The speech signal is particularly suited to this, as aspects of escalation, including emotional arousal, are proven to easily be captured by the audio signal. A challenge of applying trained systems in real-life applications is their strong dependence on the training material and limited generalization abilities. For this reason, in this contribution, we perform an extensive analysis of three corpora in the Dutch language. All three corpora are high in escalation behavior content and are annotated on alternative dimensions related to escalation. A process of label mapping resulted in two possible ground truth estimations for the three datasets as low, medium, and high escalation levels. To observe class behavior and inter-corpus differences more closely, we perform acoustic analysis of the audio samples, finding that derived labels perform similarly across each corpus, with escalation interaction increasing in pitch (F0) and intensity (dB). We explore the suitability of different speech features, data augmentation, merging corpora for training, and testing on actor and non-actor speech through our experiments. We find that the extent to which merging corpora is successful depends greatly on the similarities between label definitions before label mapping. Finally, we see that the escalation recognition task can be performed in a cross-corpus setup with hand-crafted speech features, obtaining up to 63.8% unweighted average recall (UAR) at best for a cross-corpus analysis, an increase from the inter-corpus results of 59.4% UAR.
Ceramic Toughening Strategies for Biomedical Applications

Aiming at shortage of metal materials, ceramic is increasingly applied in biomedicine due to its high strength, pleasing esthetics and good biocompatibility, especially for dental restorations and implants, artificial joints, as well as synthetic bone substitutes. However, the inherent brittleness of ceramic could lead to serious complications, such as fracture and disfunction of biomedical devices, which impede their clinical applications. Herein, several toughening strategies have been summarized in this review, including reinforcing phase addition, surface modification, and manufacturing processes improvement. Doping metal and/or non-metal reinforcing fillers modifies toughness of bulk ceramic, while surface modifications, mainly coating, chemical and thermal methods, regulate toughness on the surface layer. During fabrication, optimization should be practiced in powder preparation, green forming and densification processes. Various toughening strategies utilize mechanisms involving fine-grained, stress-induced phase transformation, and microcrack toughening, as well as crack deflection, bifurcation, bridging and pull-out. This review hopes to shed light on systematic combination of different toughening strategies and mechanisms to drive progress in biomedical devices.
Pathways of Parental Education on Children's and Adolescent's Body Mass Index: The Mediating Roles of Behavioral and Psychological Factors

Aim The increasing body mass index (BMI) often followed by overweight and obesity is a global health problem of the 21st century. Children and adolescents with lower socioeconomic status are more affected than their counterparts. The mechanisms behind these differences must be well understood to develop effective prevention strategies. This analysis aims at examining the association of parental education as an indicator of the socioeconomic status on children's and adolescent's body mass index and the role of behavioral and psychological risk factors for a higher BMI longitudinally. Methods The analysis was based on a nationwide sample of N = 460 children and adolescents, aged 11 to 17 at baseline (2009–2012), who took part in the representative BELLA study, the mental health module of the German National Health Interview and Examination Survey among Children and Adolescents (KiGGS). A follow-up was conducted 5 years later. Using mediation analyses, the mediating effects of breakfast consumption, consumption of sugar-sweetened beverages, screen time, physical activity, mental health problems (Strengths and Difficulties Questionnaire), and health-related quality of life (KIDSCREEN-10) on the association of parent's years of education on their children's BMI were investigated. Results A lower level of parental education was significantly associated with a higher BMI in children and adolescents 5 years later. The association was partially mediated by breakfast consumption and total screen time, with breakfast consumption mediating 16.7% and total screen time 27.8% of the association. After controlling for age, gender, and migration status, only breakfast consumption remained a partial mediator (8.5%). Other included variables had no mediating effects. Conclusions Preventive measures should be mainly targeted at children and adolescents of parents with lower educational levels. Tailored strategies to prevent the development of overweight and obesity in this population among children and adolescents should promote daily breakfast consumption at home and reducing screen time.
Passive and active two-dimensional photonic crystal components

Photonic crystals are periodic dielectric structures having periodicity of the order of the wavelength. Consequently, they o er the ability to control the propagation of electromagnetic waves in a similar way as the periodic potential a ects the electron motion in a semiconductor crystal. By choosing the parameters of the photonic crystal, desired dispersion characteristics such as band gaps for light can be implemented, providing the possibility of creating miniaturized photonic components for integrated optical circuits. In this thesis, two-dimensional photonic crystal components with passive and active functionalities are designed, realized and investigated. The passive components, including photonic crystal cavities, waveguides and tight waveguide bends, are studied by means of fareld and neareld (heterodyne SNOM) measurement techniques addressing loss, quality factors and transmission e ciencies. The ability to tune or modulate the optical properties of photonic crystal devices increases their functionality and opens up new possibilities for applications. We present two ways of perturbing the optical environment near a photonic crystal cavity, enabling tuning and modulation of the in-plane transmission. Optical switching and wavelength tuning is obtained by means of induced thermal and plasma dispersion e ects when focusing a laser onto a photonic crystal cavity structure, demonstrating the feasibility of high-speed optical integrated circuits based on silicon structures. On the other hand, tuning of the resonant wavelength and on-o switching of the transmission signal is achieved by probing the optical eld con ned within the resonant cavity by means of an atomic force microscope (AFM) tip, suggesting an integrated on-o switch or tunable lter. This thesis combines design, fabrication and measurement, thus bringing a better understanding of the fundamental properties of these types of photonic crystals, and helping to pave the way to practical integrated optical circuits.
Exploring the Cunninghamia lanceolata(Lamb.) Hook Genome by BAC Sequencing

Cunninghamia lanceolata (Lamb.)Hook is an important economic timber tree in China. However, its genome characteristics have not been extensively assessed. To better understand its genome information, the bacterial artificial chromosome (BAC) library of chinese fir was constructed. A total of 422 BAC clones were selected and divided into 10 pools and sequenced, and with an average insert size of 121 kb, ranging from 97 to 145 kb. A total of 61,902,523 bp of reference sequences were sequenced and assembled, and based on an estimated genome size of 11.6 Gb for Chinese fir, the BAC library was estimated to have a total coverage of 0.53% genome equivalents. Bioinformatics analyses were also performed for repeated sequences, tRNAs, coding gene prediction, and functional annotation. The results of this study provide insights into the brief structure of the Chinese fir genome and has generated gene data that will facilitate molecular investigations on the mechanisms underlying tree growth.
Pruritus: A Sensory Symptom Generated in Cutaneous Immuno-Neuronal Crosstalk

Pruritus or itch generated in the skin is one of the most widespread symptoms associated with various dermatological and systemic (immunological) conditions. Although many details about the molecular mechanisms of the development of both acute and chronic itch were uncovered in the last 2 decades, our understanding is still incomplete and the clinical management of pruritic conditions is one of the biggest challenges in daily dermatological practice. Recent research revealed molecular interactions between pruriceptive sensory neurons and surrounding cutaneous cell types including keratinocytes, as well as resident and transient cells of innate and adaptive immunity. Especially in inflammatory conditions, these cutaneous cells can produce various mediators, which can contribute to the excitation of pruriceptive sensory fibers resulting in itch sensation. There also exists significant communication in the opposite direction: sensory neurons can release mediators that maintain an inflamed, pruritic tissue-environment. In this review, we summarize the current knowledge about the sensory transduction of pruritus detailing the local intercellular interactions that generate itch. We especially emphasize the role of various pruritic mediators in the bidirectional crosstalk between cutaneous non-neuronal cells and sensory fibers. We also list various dermatoses and immunological conditions associated with itch, and discuss the potential immune-neuronal interactions promoting the development of pruritus in the particular diseases. These data may unveil putative new targets for antipruritic pharmacological interventions.
Intracranial Metastatic Disease: Present Challenges, Future Opportunities

Intracranial metastatic disease (IMD) is a prevalent complication of cancer that significantly limits patient survival and quality of life. Over the past half-century, our understanding of the epidemiology and pathogenesis of IMD has improved and enabled the development of surveillance and treatment algorithms based on prognostic factors and tumor biomolecular characteristics. In addition to advances in surgical resection and radiation therapy, the treatment of IMD has evolved to include monoclonal antibodies and small molecule antagonists of tumor-promoting proteins or endogenous immune checkpoint inhibitors. Moreover, improvements in the sensitivity and specificity of imaging as well as the development of new serological assays to detect brain metastases promise to revolutionize IMD diagnosis. In this review, we will explore current treatment principles in patients with IMD, including the emerging role of targeted and immunotherapy in select primary cancers, and discuss potential areas for further investigation.
Pain and the Triple Network Model

Acute pain is a physiological response that causes an unpleasant sensory and emotional experience in the presence of actual or potential tissue injury. Anatomically and symptomatically, chronic pathological pain can be divided into three distinct but interconnected pathways, a lateral “painfulness” pathway, a medial “suffering” pathway and a descending pain inhibitory circuit. Pain (fullness) can exist without suffering and suffering can exist without pain (fullness). The triple network model is offering a generic unifying framework that may be used to understand a variety of neuropsychiatric illnesses. It claims that brain disorders are caused by aberrant interactions within and between three cardinal brain networks: the self-representational default mode network, the behavioral relevance encoding salience network and the goal oriented central executive network. A painful stimulus usually leads to a negative cognitive, emotional, and autonomic response, phenomenologically expressed as pain related suffering, processed by the medial pathway. This anatomically overlaps with the salience network, which encodes behavioral relevance of the painful stimuli and the central sympathetic control network. When pain lasts longer than the healing time and becomes chronic, the pain- associated somatosensory cortex activity may become functionally connected to the self-representational default mode network, i.e., it becomes an intrinsic part of the self-percept. This is most likely an evolutionary adaptation to save energy, by separating pain from sympathetic energy-consuming action. By interacting with the frontoparietal central executive network, this can eventually lead to functional impairment. In conclusion, the three well-known pain pathways can be combined into the triple network model explaining the whole range of pain related co-morbidities. This paves the path for the creation of new customized and personalized treatment methods.
Etiologic Classification of 541 Infantile Spasms Cases: A Cohort Study

Objective To explore the etiology of infantile spasms (IS) in a large Chinese cohort based on the United States National Infantile Spasms Consortium (NISC) classification. Methods In the present study, we recruited IS patients diagnosed at a single center (Xiangya Hospital, Central South University) between Jan 2010 and Aug 2019. Thereafter, we collected their clinical and genetic information retrospectively. Their underlying etiologies were classified according to the NISC classification and then compared in different scenarios to understand their distribution. Results A total of 541 patients with IS from 18 provinces were included in this study. The underlying etiology was identified in 53.2% of the cases: structural-acquired, 25.3%; genetic, 12.9%; genetic-structural, 7.2%; structural-congenital, 5.0%; metabolic, 2.4%; infections, 0.4% and immune, 0%. Whole-exome sequencing (WES) provided the highest diagnostic yield (26.9%). In structural-acquired IS, the proportion of hypoglycemic brain injuries was significant, second only to hypoxic-ischemic encephalopathy. There was no patient discovered to have Down syndrome. STXBP1, CDKL5, TSC2, KCNQ2, IRF2BPL, and TSC1 were the most frequently implicated genes. Genetic causes were found to be the most common cause of IS in the early onset group, while structural-acquired etiologies were common in males and preterm babies. Patients with pre-spasm seizures were associated with a higher proportion of identified causes than those without. Non-acquired structural etiologies were more common in patients without hypsarrhythmia than in those with hypsarrhythmia. Significance The most prevalent cause of IS was structural acquired followed by genetic causes. When brain MRI fails to detect the etiology, we propose WES as the next step. Structural-acquired IS and cases with genetic disorders are characteristic of the Chinese cohort, however, the etiology differs with the patient's age of onset, gestation age at birth, sex, and the presence/absence of both pre-spasm seizures, and hypsarrhythmia.