Miracle-dz/UniFAR-FTUs huggingface dataset:
How Universities Have Betrayed Reason and Humanity—And What's to Be Done About It

In 1984 the author published From Knowledge to Wisdom, a book that argues that a revolution in academia is urgently needed, so that problems of living, including global problems, are put at the heart of the enterprise, and the basic aim becomes to seek and promote wisdom, and not just acquire knowledge. Every discipline and aspect of academia needs to change, and the whole way in which academia is related to the rest of the social world. Universities devoted to the pursuit of knowledge and technological know-how betray reason and, as a result, betray humanity. As a result of becoming more intellectually rigorous, academic inquiry becomes of far greater benefit to humanity. If the revolution argued for all those years ago had been taken up and put into academic practice, we might now live in a much more hopeful world than the one that confronts us. Humanity might have begun to learn how to solve global problems; the Amazon rain forests might not face destruction; we might not be faced with mass extinction of species; Brexit might not have been voted for in the UK in 2016, and Trump might not have been elected President in the USA. An account is given of work published by the author during the years 1972–2021 that expounds and develops the argument. The conclusion is that we urgently need to create a high-profile campaign devoted to transforming universities in the way required so that humanity may learn how to make social progress toward a better, wiser, more civilized, enlightened world.
Adjuvant EGFR-TKIs for Patients With Resected EGFR-Mutant Non-Small Cell Lung Cancer: A Meta-Analysis of 1,283 Patients

Background Cisplatin-based chemotherapy was previously considered as the standard adjuvant therapy for improved overall survival (OS) in patients with non-small cell lung cancer (NSCLC) after surgery. However, the benefit was limited due to high risks of recurrence and adverse events. In the present study, the efficacy of adjuvant epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for EGFR-mutant patients after surgery was investigated using the latest updated data. Methods This meta-analysis included a comprehensive range of relevant studies identified from database searches. Disease-free survival (DFS) and OS with hazard ratios (HRs) were calculated using random-effect or fixed-effect models. Subgroup analysis was also performed. Results A total of seven randomized clinical trials were included in the meta-analysis and involved 1,283 NSCLC patients harboring EGFR mutations. In resected EGFR-mutant NSCLC patients, adjuvant EGFR-TKIs were significantly better than chemotherapy in terms of DFS (HR: 0.41; 95%CI: 0.24–0.70, P = 0.001), without showing any benefit in OS (HR: 0.72; 95%CI: 0.37–1.41, P = 0.336). No significant difference in DFS was observed between patients with EGFR exon 19 deletion and those with L858R mutation. Resected EGFR-mutant NSCLC patients treated with osimertinib experienced improved DFS and a lower risk of brain recurrence than those treated with gefitinib or erlotinib. Adjuvant EGFR-TKIs reduced the risk of bone and lung relapse, without decreasing the risk of local recurrence and liver relapse. Conclusion This meta-analysis shows that adjuvant EGFR-TKI therapy could significantly prolong DFS in patients with resected EGFR-mutant NSCLC. Treatment with osimertinib showed improved DFS with a lower risk of brain recurrence than treatment with gefitinib or erlotinib for resected disease.
Microalbuminuria After Kidney Transplantation Predicts Cardiovascular Morbidity

Background: Microalbuminuria is a well-characterized marker of kidney malfunction, both in diabetic and non-diabetic populations, and is used as a prognostic marker for cardiovascular morbidity and mortality. A few studies implied that it has the same value in kidney transplanted patients, but the information relies on spot or dipstick urine protein evaluations, rather than the gold standard of timed urine collection. Methods: We revisited a cohort of 286 kidney transplanted patients, several years after completing a meticulously timed urine collection and assessed the prevalence of major cardiovascular adverse events (MACE) in relation to albuminuria. Results: During a median follow up of 8.3 years (IQR 6.4–9.1) 144 outcome events occurred in 101 patients. By Kaplan-Meier analysis microalbuminuria was associated with increased rate of CV outcome or death (p = 0.03), and this was still significant after stratification according to propensity score quartiles (p = 0.048). Time dependent Cox proportional hazard analysis showed independent association between microalbuminuria and CV outcomes 2 years following microalbuminuria detection (HR 1.83, 95% CI 1.07–2.96). Conclusions: Two years after documenting microalbuminuria in kidney transplanted patients, their CVD risk was increased. There is need for primary prevention strategies in this population and future studies should address the topic.
Differences and Similarities in the Contributions of Phonological Awareness, Orthographic Knowledge and Semantic Competence to Reading Fluency in Chinese School-Age Children With and Without Hearing Loss

Compared with the large number of studies on reading of children with hearing loss (HL) in alphabetic languages, there are only a very limited number of studies on reading of Chinese-speaking children with HL. It remains unclear how phonological, orthographic, and semantic skills contribute to reading fluency of Chinese school-age children with HL. The present study explored this issue by examining the performances of children with HL on reading fluency and three linguistic skills compared with matched controls with normal hearing (NH). Specifically, twenty-eight children with HL and 28 chronological-age-matched children with NH were tested on word/sentence reading fluency (WRF/SRF), phonological awareness (PA) which was composed of onset/vowel/lexical tone awareness, orthographic knowledge (OK), and semantic competence (SC) which comprised animal word identification, pseudo-homophone detection, and word segmentation. Results showed that children with HL lagged behind their peers with NH in WRF/SRF and most of the phonological, orthographic, and semantic subskills except onset awareness and pseudo-homophone detection. Furthermore, the significant contributors to WRF differed between the two groups with PA being the significant contributor in the children with NH while OK being the significant contributor in the children with HL. However, the significant contributor to SRF did not differ between the two groups with SC being the only significant contributor. These results revealed not only between-group differences but also similarities in the relative contributions of PA, OK, and SC to reading fluency at both word and sentence levels, which has practical implications for developing better training programs to improve reading for children with HL.
New and More Solitary Wave Solutions for the Klein-Gordon-Schrödinger Model Arising in Nucleon-Meson Interaction

This paper considers methods to extract exact, explicit, and new single soliton solutions related to the nonlinear Klein-Gordon-Schrödinger model that is utilized in the study of neutral scalar mesons associated with conserved scalar nucleons coupled through the Yukawa interaction. Three state of the art integration schemes, namely, the e−Φ(ξ)-expansion method, Kudryashov's method, and the tanh-coth expansion method are employed to extract bright soliton, dark soliton, periodic soliton, combo soliton, kink soliton, and singular soliton solutions. All the constructed solutions satisfy their existence criteria. It is shown that these methods are concise, straightforward, promising, and reliable mathematical tools to untangle the physical features of mathematical physics equations.
Temperature induced complementary switching in titanium oxide resistive random access memory

On the way towards high memory density and computer performance, a considerable development in energy efficiency represents the foremost aspiration in future information technology. Complementary resistive switch consists of two antiserial resistive switching memory (RRAM) elements and allows for the construction of large passive crossbar arrays by solving the sneak path problem in combination with a drastic reduction of the power consumption. Here we present a titanium oxide based complementary RRAM (CRRAM) device with Pt top and TiN bottom electrode. A subsequent post metal annealing at 400°C induces CRRAM. Forming voltage of 4.3 V is required for this device to initiate switching process. The same device also exhibiting bipolar switching at lower compliance current, Ic <50 μA. The CRRAM device have high reliabilities. Formation of intermediate titanium oxi-nitride layer is confirmed from the cross-sectional HRTEM analysis. The origin of complementary switching mechanism have been discussed with AES, HR.
In Vivo Characterization of Cortical and White Matter Microstructural Pathology in Growth Hormone-Secreting Pituitary Adenoma

Background The growth hormone (GH) and insulin-like-growth factor 1 (IGF-1) axis has long been recognized for its critical role in brain growth, development. This study was designed to investigate microstructural pathology in the cortex and white matter in growth hormone-secreting pituitary adenoma, which characterized by excessive secretion of GH and IGF-1. Methods 29 patients with growth hormone-secreting pituitary adenoma (acromegaly) and 31 patients with non-functional pituitary adenoma as controls were recruited and assessed using neuropsychological test, surface-based morphometry, T1/T2-weighted myelin-sensitive magnetic resonance imaging, neurite orientation dispersion and density imaging, and diffusion tensor imaging. Results Compared to controls, we found 1) acromegaly had significantly increased cortical thickness throughout the bilateral cortex (pFDR < 0.05). 2) T1/T2-weighted ratio in the cortex were decreased in the bilateral occipital cortex and pre/postcentral central gyri but increased in the bilateral fusiform, insular, and superior temporal gyri in acromegaly (pFDR < 0.05). 3) T1/T2-weighted ratio were decreased in most bundles, and only a few areas showed increases in acromegaly (pFDR < 0.05). 4) Neurite density index (NDI) was significantly lower throughout the cortex and bundles in acromegaly (pTFCE < 0.05). 5) lower fractional anisotropy (FA) and higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in extensive bundles in acromegaly (pTFCE < 0.05). 6) microstructural pathology in the cortex and white matter were associated with neuropsychological dysfunction in acromegaly. Conclusions Our findings suggested that long-term persistent and excess serum GH/IGF-1 levels alter the microstructure in the cortex and white matter in acromegaly, which may be responsible for neuropsychological dysfunction.
Proteome-Wide Analysis of Heat-Stress in Pinus radiata Somatic Embryos Reveals a Combined Response of Sugar Metabolism and Translational Regulation Mechanisms

Somatic embryogenesis is the process by which bipolar structures with no vascular connection with the surrounding tissue are formed from a single or a group of vegetative cells, and in conifers it can be divided into five different steps: initiation, proliferation, maturation, germination and acclimatization. Somatic embryogenesis has long been used as a model to study the mechanisms regulating stress response in plants, and recent research carried out in our laboratory has demonstrated that high temperatures during initial stages of conifer somatic embryogenesis modify subsequent phases of the process, as well as the behavior of the resulting plants ex vitro. The development of high-throughput techniques has facilitated the study of the molecular response of plants to numerous stress factors. Proteomics offers a reliable image of the cell status and is known to be extremely susceptible to environmental changes. In this study, the proteome of radiata pine somatic embryos was analyzed by LC-MS after the application of high temperatures during initiation of embryonal masses [(23°C, control; 40°C (4 h); 60°C (5 min)]. At the same time, the content of specific soluble sugars and sugar alcohols was analyzed by HPLC. Results confirmed a significant decrease in the initiation rate of embryonal masses under 40°C treatments (from 44 to 30.5%) and an increasing tendency in the production of somatic embryos (from 121.87 to 170.83 somatic embryos per gram of embryogenic tissue). Besides, heat provoked a long-term readjustment of the protein synthesis machinery: a great number of structural constituents of ribosomes were increased under high temperatures, together with the down-regulation of the enzyme methionine-tRNA ligase. Heat led to higher contents of heat shock proteins and chaperones, transmembrane transport proteins, proteins related with post-transcriptional regulation (ARGONAUTE 1D) and enzymes involved in the synthesis of fatty acids, specific compatible sugars (myo-inositol) and cell-wall carbohydrates. On the other hand, the protein adenosylhomocysteinase and enzymes linked with the glycolytic pathway, nitrogen assimilation and oxidative stress response were found at lower levels.
Phytoconstituents, In Vitro Anti-Infective Activity of Buddleja indica Lam., and In Silico Evaluation of its SARS-CoV-2 Inhibitory Potential

Phytochemical investigation of Buddleja indica Lam. leaves methanol extract (BIT) resulted in the isolation of six known compounds for the first time from the plant, namely, p-hydroxybenzoic acid 1), caffeic acid 2), quercetin 3-O-β-D glucoside-7-O-α-L-rhamnoside 3), kaempferol 3-O-β-D glucoside-7-O-α-L-rhamnoside 4), quercetin 7-O-β-D glucoside 5) and kaempferol 6). BIT extract showed potent antibacterial activity with MIC values ranging between 0.48 and 1.95 μg/ml with Bacillus subtilis was the most susceptible to the BIT effect. It showed a notable antimycobacterial and anti-Helicobacter pylori activity with MIC values of 100 and 80 μg/ml, respectively. Vesicular stomatitis virus (VSV) was more sensitive to the antiviral activity of BIT comparable to herpes simplex virus type 1 (HSV-1), showing 48.38 and 41.85% inhibition of the viral replication at a dose of 50 μg/ml for VSV and HSV-1, respectively. In silico molecular docking of the isolated compounds revealed that caffeic acid 2) showed the highest fitting within the active sites of DNA-gyrase, topoisomerase IV, and SARS-CoV-2 MPro. Quercetin 7-O-β-D glucoside 5) revealed the best fitting in dihydrofolate reductase active site with ∆ G value equals −36.53 Kcal/mol. Kaempferol 6) exhibited the highest fitting towards β-lactamase, SARS-CoV-2PLpro, and SARS-CoV-2 3CLpro active sites. Thus, B. indica Lam. can be considered as a future source of cheap, substantially safe, and credible antibacterial, antifungal, and antiviral candidate of natural origin that could effectively participate in solving the problem of COVID-19 pandemic. These findings provide a scientific consolidation for the ethnomedicinal uses of Buddleja indica Lam. as a topical antiseptic.
GADTI: Graph Autoencoder Approach for DTI Prediction From Heterogeneous Network

Identifying drug–target interaction (DTI) is the basis for drug development. However, the method of using biochemical experiments to discover drug-target interactions has low coverage and high costs. Many computational methods have been developed to predict potential drug-target interactions based on known drug-target interactions, but the accuracy of these methods still needs to be improved. In this article, a graph autoencoder approach for DTI prediction (GADTI) was proposed to discover potential interactions between drugs and targets using a heterogeneous network, which integrates diverse drug-related and target-related datasets. Its encoder consists of two components: a graph convolutional network (GCN) and a random walk with restart (RWR). And the decoder is DistMult, a matrix factorization model, using embedding vectors from encoder to discover potential DTIs. The combination of GCN and RWR can provide nodes with more information through a larger neighborhood, and it can also avoid over-smoothing and computational complexity caused by multi-layer message passing. Based on the 10-fold cross-validation, we conduct three experiments in different scenarios. The results show that GADTI is superior to the baseline methods in both the area under the receiver operator characteristic curve and the area under the precision–recall curve. In addition, based on the latest Drugbank dataset (V5.1.8), the case study shows that 54.8% of new approved DTIs are predicted by GADTI.
Prevalence and Therapy Rates for Stuttering, Cluttering, and Developmental Disorders of Speech and Language: Evaluation of German Health Insurance Data

Purpose To evaluate the prevalence and treatment patterns of speech and language disorders in Germany. Methods A retrospective analysis of data collected from 32% of the German population, insured by the statutory German health insurance (AOK, Local Health Care Funds). We used The International Statistical Classification of Diseases and Related Health Problems, 10th revision, German Modification (ICD-10 GM) codes for stuttering (F98.5), cluttering (F98.6), and developmental disorders of speech and language (F80) to identify prevalent and newly diagnosed cases each year. Prescription and speech therapy reimbursement data were used to evaluate treatment patterns. Results In 2017, 27,977 patients of all ages were diagnosed with stuttering (21,045 males, 75% and 6,932 females, 25%). Stuttering prevalence peaks at age 5 years (boys, 0.89% and girls, 0.40%). Cluttering was diagnosed in 1,800 patients of all ages (1,287 males, 71.5% and 513 females, 28.5%). Developmental disorders of speech and language were identified in 555,774 AOK-insurants (61.2% males and 38.8% females). Treatment data indicate a substantial proportion newly diagnosed stuttering individuals receive treatment (up to 45% of 6-year-old patients), with slightly fewer than 20 sessions per year, on average. We confirmed a previous study showing increased rates of atopic disorders and neurological and psychiatric comorbidities in individuals with stuttering, cluttering, and developmental disorders of speech and language. Conclusion This is the first nationwide study using health insurance data to analyze the prevalence and newly diagnosed cases of a speech and language disorder. Prevalence and gender ratio data were consistent with the international literature. The crude prevalence of developmental disorders of speech and language increased from 2015 to 2018, whereas the crude prevalence for stuttering remained stable. For cluttering, the numbers were too low to draw reliable conclusions. Proportional treatment allocation for stuttering peaked at 6 years of age, which is the school entrance year, and is later than the prevalence peak of stuttering.
Illumination of Molecular Pathways in Multiple Sclerosis Lesions and the Immune Mechanism of Matrine Treatment in EAE, a Mouse Model of MS

The etiology of multiple sclerosis (MS) is not clear, and the treatment of MS presents a great challenge. This study aimed to investigate the pathogenesis and potential therapeutic targets of MS and to define target genes of matrine, a quinolizidine alkaloid component derived from the root of Sophorae flavescens that effectively suppressed experimental autoimmune encephalomyelitis (EAE), an animal model of MS. To this end, the GSE108000 gene data set in the Gene Expression Omnibus Database, which included 7 chronic active MS lesions and 10 control samples of white matter, was analyzed for differentially expressed genes (DEGs). X cell was used to analyze the microenvironmental differences in brain tissue samples of MS patients, including 64 types of immune cells and stromal cells. The biological functions and enriched signaling pathways of DEGs were analyzed by multiple approaches, including GO, KEGG, GSEA, and GSVA. The results by X cell showed significantly increased numbers of immune cell populations in the MS lesions, with decreased erythrocytes, megakaryocytes, adipocytes, keratinocytes, endothelial cells, Th1 cells and Tregs. In GSE108000, there were 637 DEGs, including 428 up-regulated and 209 down-regulated genes. Potential target genes of matrine were then predicted by the network pharmacology method of Traditional Chinese medicine, and 12 key genes were obtained by cross analysis of the target genes of matrine and DEGs in MS lesions. Finally, we confirmed by RT-PCR the predicted expression of these genes in brain tissues of matrine-treated EAE mice. Among these genes, 2 were significantly downregulated and 6 upregulated by matrine treatment, and the significance of this gene regulation was further investigated. In conclusion, our study defined several possible matrine target genes, which can be further elucidated as mechanism(s) of matrine action, and novel targets in the treatment of MS.
Cocaine Reduces the Neuronal Population While Upregulating Dopamine D2-Receptor-Expressing Neurons in Brain Reward Regions: Sex-Effects

Addiction to cocaine is associated with dysfunction of the dopamine mesocortical system including impaired dopamine-2 receptor (D2r) signaling. However, the effects of chronic cocaine on neuronal adaptations in this system have not been systematically examined and data available is mostly from males. Here, we investigated changes in the total neuronal density and relative concentration of D2r-expressing neurons in the medial prefrontal cortex (mPFC), dorsal striatum (Dstr), nucleus accumbens (NAc), and ventral tegmental area (VTA) in both male and female mice passively exposed to cocaine for two weeks. In parallel experiments, we measured mRNA levels for Drd2 and for opioid peptides (mPenk and mPdyn). Through a combination of large field of view fluorescent imaging with BAC transgenic D2r-eGFP mice and immunostaining, we observed that cocaine exposed mice had a higher density of D2r-positive cells that was most prominent in mPFC and VTA and larger for females than for males. This occurred amidst an overall significant decrease in neuronal density (measured with NeuN) in both sexes. However, increases in Drd2 mRNA levels with cocaine were only observed in mPFC and Dstr in females, which might reflect the limited sensitivity of the method. Our findings, which contrast with previous findings of cocaine-induced downregulation of D2r binding availability, could reflect a phenotypic shift in neurons that did not previously express Drd2 and merits further investigation. Additionally, the neuronal loss particularly in mPFC with chronic cocaine might contribute to the cognitive impairments observed with cocaine use disorder.