Miracle-dz/UniFAR-FTUs huggingface dataset:
3Cnet: pathogenicity prediction of human variants using multitask learning with evolutionary constraints

Abstract Motivation Improvements in next-generation sequencing have enabled genome-based diagnosis for patients with genetic diseases. However, accurate interpretation of human variants requires knowledge from a number of clinical cases. In addition, manual analysis of each variant detected in a patient's genome requires enormous time and effort. To reduce the cost of diagnosis, various computational tools have been developed to predict the pathogenicity of human variants, but the shortage and bias of available clinical data can lead to overfitting of algorithms. Results We developed a pathogenicity predictor, 3Cnet, that uses recurrent neural networks to analyze the amino acid context of human variants. As 3Cnet is trained on simulated variants reflecting evolutionary conservation and clinical data, it can find disease-causing variants in patient genomes with 2.2 times greater sensitivity than currently available tools, more effectively discovering pathogenic variants and thereby improving diagnosis rates. Availability and implementation Codes (https://github.com/KyoungYeulLee/3Cnet/) and data (https://zenodo.org/record/4716879#.YIO-xqkzZH1) are freely available to non-commercial users. Supplementary information Supplementary data are available at Bioinformatics online.
Neuroscience Education as Therapy for Migraine and Overlapping Pain Conditions: A Scoping Review.

BACKGROUND Neuroscience Education Therapy (NET) has been successfully used for numerous overlapping pain conditions, but few studies have investigated NET for migraine. OBJECTIVE We sought to (1) review the literature on NET used for the treatment of various pain conditions to assess how NET has been studied thus far and (2) recommend considerations for future research of NET for the treatment of migraine. DESIGN/METHODS Following the PRISMA guideline for scoping reviews (PRISMA-ScR) Co-author (TR), a Medical Librarian, searched the MEDLINE, PsychInfo, Embase & Cochrane Central Clinical Trials Registry databases for peer-reviewed articles describing NET to treat migraine and other chronic pain conditions. Each citation was reviewed by two trained independent reviewers. Conflicts were resolved through consensus. RESULTS Overall, a NET curriculum consists of the following topics: pain does not equate to injury, pain is generated in the brain, perception, genetics, reward systems, fear, brain plasticity, and placebo/nocebo effects. Delivered through individual, group, or a combination of individual and group sessions, NET treatments often incorporate exercise programs and/or components of other evidence-based behavioral treatments. NET has significantly reduced catastrophizing, kinesiophobia, pain intensity, and disability in overlapping pain conditions. In migraine-specific studies, when implemented together with traditional pharmacological treatments, NET has emerged as a promising therapy by reducing migraine days, pain intensity and duration, and acute medication intake. CONCLUSION NET is an established treatment for pain conditions, and future research should focus on refining NET for migraine, examining delivery modality, dosage, components of other behavioral therapies to integrate, and migraine-specific NET curricula.
Hypoxic Stem Cell-derived Extracellular Vesicles for Cardiac Repair in Preclinical Animal Models of Myocardial Infarction: a Meta-analysis.

Given that the modification of stem cell-derived Extracellular Vesicles (EV) can enhance their regenerative efficiency, an increasing number of studies pay attention to the therapeutic potential of hypoxic preconditioning of stem cell-derived EVs (Hypo-EVs) in cardiac repair. Our meta-analysis aims to evaluate the cardiac repair of Hypo-EVs in preclinical animal models of Myocardial Infarction (MI). We searched PubMed, EMBASE, and the Web of Science up to January 2021. The primary outcome was left ventricular ejection fraction (LVEF). The second outcomes were left ventricular fractional shortening (LVFS) and infarct size. Random-effects modelling was used to calculate pooled weighted mean differences (WMDs) and 95% CIs. Nine studies satisfied the inclusion criteria. Compared with the model group, pooled analyses demonstrated that stem cell-derived EVs culturing in normal oxygen environment (Nor-EVs) can improve LVEF (WMD 9.07, 95% CI 6.76 to 11.38, I2= 80.7%), LVFS (WMD 3.03, 95% CI 0.79 to 5.27, I2= 86.3%) and reduce infarct size (WMD -12.15, 95% CI -19.12 to -5.18, I2= 96.8%). Compared with Nor-EVs, Hypo-EVs can improve LVEF (WMD 5.11, 95% CI 1.63 to 8.60, I2= 95%), LVFS (WMD 6.54, 95% CI 4.08 to 8.99, I2= 90.6%), and reduce infarct size (WMD -7.42, 95% CI -12.97 to -1.87, I2= 97.2%). These results suggest that Hypo-EVs could show more improvement than Nor-EVs therapy on cardiac repair in the preclinical MI animal model. However, future well‑designed large animal studies might be necessary to clarify the methods and effects of Hypo-EVs therapy to help provide new ideas for future engineered EVs design.
Improving the implementation of pre-laboratory flow charts, cooperative learning and laboratory report writing in first year organic chemistry I laboratory class

The aim of this research was to use different assessment methods by engaging all students in pre-laboratory flow charts with check lists by taking into account rather than giving a mark for attendance for their presence, based on principles of cooperative learning method by forming groups, promoting positive interdependence among individuals, providing individual accountability and helping students to develop team work skills and lastly the post laboratory reports evaluation and presentation on selected criteria’s summarizes the research base that attest to the effectiveness of methods and improvement of cooperative learning in practical organic chemistry I class. [African Journal of Chemical Education—AJCE 6(1), January 2016]
Rejoinder for discussions on correct and logical causal inference for binary and time‐to‐event outcomes in randomized controlled trials

Our paper differs from previous literature in two ways: 1.We think in terms of clinical consequences, what benefits patients, what harms patients. Our main message is: using a not logic‐respecting efficacy measure can potentially harm patients in a randomized controlled trial (RCT), as we prove analytically, and demonstrate with the OAK blood‐based tumor mutational burden (bTMB) study. 2.We follow nature, which mixes effects within each treatment arm. Our secondary message is that following nature to mix within each treatment arm first before calculating any efficacy measure between treatments resolves issues. For example, following natural mixing to prove ratio of time is logic‐respecting avoids the issue that weights of efficacy measures are implicit solution to an equation that depends on the unknown prognostic effect. More importantly, coding subgroup mixable estimation (SEM) by mixing within each treatment arm first and then calculating efficacy will make marginal and conditional efficacy agree, for logic‐respecting efficacy measures (be it a ratio or a difference), no matter the outcome is continuous, binary, or time‐to‐event. One does not have to choose between marginal and conditional.
Nemertean, Brachiopod, and Phoronid Neuropeptidomics Reveals Ancestral Spiralian Signaling Systems

Abstract Neuropeptides are diverse signaling molecules in animals commonly acting through G-protein coupled receptors (GPCRs). Neuropeptides and their receptors underwent extensive diversification in bilaterians and the relationships of many peptide–receptor systems have been clarified. However, we lack a detailed picture of neuropeptide evolution in lophotrochozoans as in-depth studies only exist for mollusks and annelids. Here, we analyze peptidergic systems in Nemertea, Brachiopoda, and Phoronida. We screened transcriptomes from 13 nemertean, 6 brachiopod, and 4 phoronid species for proneuropeptides and neuropeptide GPCRs. With mass spectrometry from the nemertean Lineus longissimus, we validated several predicted peptides and identified novel ones. Molecular phylogeny combined with peptide-sequence and gene-structure comparisons allowed us to comprehensively map spiralian neuropeptide evolution. We found most mollusk and annelid peptidergic systems also in nemerteans, brachiopods, and phoronids. We uncovered previously hidden relationships including the orthologies of spiralian CCWamides to arthropod agatoxin-like peptides and of mollusk APGWamides to RGWamides from annelids, with ortholog systems in nemerteans, brachiopods, and phoronids. We found that pleurin neuropeptides previously only found in mollusks are also present in nemerteans and brachiopods. We also identified cases of gene family duplications and losses. These include a protostome-specific expansion of RFamide/Wamide signaling, a spiralian expansion of GnRH-related peptides, and duplications of vasopressin/oxytocin before the divergence of brachiopods, phoronids, and nemerteans. This analysis expands our knowledge of peptidergic signaling in spiralians and other protostomes. Our annotated data set of nearly 1,300 proneuropeptide sequences and 600 GPCRs presents a useful resource for further studies of neuropeptide signaling.
Simple mapping-based quantification of a mock microbial community using total RNA-seq data

Most microbes in the natural environment are difficult to cultivate. Thus, culture-independent analysis for microbial community structure is important for the understanding of its ecological functions. An immense ribosomal RNA sequence collection is available from phylogenetic research on organisms in all domains. These sequences are available for use in genetic research. However, the amplicon-seq process using PCR requires the construction of a sequence library. Construction can introduce bias into quantitative analyses, and each domain of species needs its own primer set. Total RNA sequencing has the advantage of analyzing an entire microbial community, including bacteria, archea, and eukaryote, at once. Such analysis yields large amounts of ribosomal RNA sequences that can be used for analysis without PCR bias. Evaluation using total RNA-seq for quantitative analysis of microbial communities and comparison with amplicon-seq is still rare. In the present study, we developed a mapping-based total RNA-seq analysis to obtain quantitative information on microbial community structure and compared our results with ordinary amplicon-seq methods. We read total RNA sequences from a commercially available mock community (ATCC MSA-2003) and divided reads into small subunit ribosomal RNA (ssrRNA) origin reads and others, such as mRNA origin reads. We then mapped ssrRNA origin reads on annotated assembled contigs and obtained quantitative results under several analysis strategies. Removal of low complexity sequences, sorting ssrRNA with paired-in mode, and performing homology-based taxonomical assignments (BLAST+ or vsearch) showed superior outcomes to other strategies. Results with this approach showed a median relative abundance among ten mock community members of ~10%; ordinary amplicon-seq showed a much lower percentage. Thus, total RNA-seq can be a powerful tool for analyzing microbial community structure and is not limited to analyzing gene expression profiling of microbiomes.
The role of personal data value, culture and self-construal in online privacy behaviour

Personal data is ubiquitous in the digital world, can be highly valuable in aggregate, and can lead to unintended intrusions for the data creator. However, individuals’ expressions of concern about exposure of their personal information are generally not matched by their behavioural caution. One reason for this mismatch could be the varied and intangible value of personal data. We present three studies investigating the potential association between personal data value and privacy behaviour, assessing both individual and cross-cultural differences in personal data valuation, comparing collectivist and individualistic cultures. Study 1a, using a representative UK sample, found no relationship between personal data value and privacy behaviour. However, Study 1b found Indian (collectivist) participants’ privacy behaviour was sensitive to personal data value, unlike US (individualist) participants. Study 2 showed that in a UK sample, privacy behaviour was sensitive to personal data value but only for individuals who think of themselves as more similar to others (i.e., self-construe as similar, rather than different). We suggest those who prioritise group memberships are more sensitive to unintentional disclosure harm and therefore behave in accordance with personal data valuations—which informs the privacy concern-behaviour relationship. Our findings can suggest approaches to encourage privacy behaviours.
The role of artificial intelligence in enhancing clinical nursing care: A scoping review.

AIM To present an overview of how artificial intelligence has been used to improve clinical nursing care. BACKGROUND Artificial intelligence has been reshaping the healthcare industry but little is known about its applicability in enhancing nursing care. METHODS A scoping review was conducted. Seven electronic databases (CINAHL, Cochrane Library, EMBASE, IEEE Xplore, PubMed, Scopus, and Web of Science) were searched from 1 January 2010 till 20 December 2020. Grey literature and reference lists of included articles were also searched. RESULTS Thirty-seven studies encapsulating the use of AI in improving clinical nursing care were included in this review. Six use cases were identified - documentation, formulating nursing diagnoses, formulating nursing care plans, patient monitoring, patient care prediction such as falls prediction (most common) and wound management. Various techniques of machine learning and classification were used for predictive analyses and to improve nurses' preparedness and management of patients' conditions. CONCLUSIONS This review highlighted the potential of artificial intelligence in improving the quality of nursing care. However, more randomized controlled trials in real-life healthcare settings should be conducted to enhance the rigor of evidence. IMPLICATIONS FOR NURSING MANAGEMENT Education in the application of artificial intelligence should be promoted to empower nurses to lead technological transformations and not passively trail behind others.
Spatially Fractionated X-Ray Microbeams Elicit a More Sustained Immune and Inflammatory Response in the Brainstem than Homogenous Irradiation

Synchrotron microbeam radiation therapy (MRT) is a preclinical irradiation technique which could be used to treat intracranial malignancies. The goal of this work was to discern differences in gene expression and the predicted regulation of molecular pathways in the brainstem after MRT versus synchrotron broad-beam radiation therapy (SBBR). Healthy C57BL/6 mice received whole-head irradiation with median acute toxic doses of MRT (241 Gy peak dose) or SBBR (13 Gy). Brains were harvested 4 and 48 h postirradiation and RNA was extracted from the brainstem. RNA-sequencing was performed to identify differentially expressed genes (false discovery rate < 0.01) relative to nonirradiated controls and significantly regulated molecular pathways and biological functions were identified (Benjamini-Hochberg corrected P < 0.05). Differentially expressed genes and regulated pathways largely reflected a pro-inflammatory response 4 h after both MRT and SBBR which was sustained at 48 h postirradiation for MRT. Pathways relating to radiation-induced viral mimicry, including HMGB1, NF-κB and interferon signaling cascades, were predicted to be uniquely activated by MRT. Local microglia, as well as circulating leukocytes, including T cells, were predicted to be activated by MRT. Our findings affirm that the transcriptomic signature of MRT is distinct from broad-beam radiotherapy, with a sustained inflammatory and immune response up to 48 h postirradiation.
Discovery of New Calcium Etidronates Employing Ultrasound Adapted High-Throughput Methods

The formation of calcium etidronates was investigated employing high-throughput ultrasonic synthesis. In the study of the system CaCl2/H2O3P-C(OH)(CH3)-PO3H2/H2O/KOH three new crystalline products were obtained in dependence of the deprotonation degree of the bisphosphonic acid HEDP (1-hydroxyethylidene-1,1-diphosphonic acid, H2O3P-C(OH)(CH3)-PO3H2) and the sonication time. In a large region of the parameter space and at short reaction times [Ca(HO3P-C(OH)(CH3)-PO3H)(H2O)]·2.5H2O (1) forms. At higher pH [KCa(HO3P-C(OH)(CH3)-PO3)(H2O)]·H2O (2) containing the asymmetrically deprotonated HO3P-C(OH)(CH3)-PO33– ion and [K2Ca(O3P-C(OH)(CH3)-PO3)(H2O)6] (3) with the fully deprotonated ligand are obtained. The crystal structures of 1 and 2 were solved and refined from X-ray powder diffraction data. The thermal decomposition of the compounds was investigated. If exposed to moderate temperatures 1.5 water molecules per formula unit are removed from the crystal structure of 1 and the pseudopolymorphic compound [Ca(H.
Comparison of efficacy and safety of complementary and alternative therapies for essential hypertension with anxiety or depression disorder

Background Essential hypertension (EH) with anxiety or depression belongs to the category of psycho-cardiology. Hypertension is closely related to anxiety and depression. The adverse reactions of Western medicine are apparent and the compliance is poor. Supplementary and replacement therapies have accumulated rich experience in clinical practices, which can reduce side effects and improve clinical efficacy. This study intends to use the Bayesian network meta-analysis (NMA) analysis method for the first time to gather randomized controlled trials (RCTs) related to complementary and alternative therapies in the treatment of hypertension with anxiety or depression disorder and rank efficacy and safety, to provide a reference basis for the treatment of hypertension with anxiety or depression disorder. Methods All randomized controlled trials (RCTs) and registered and ongoing trials of Chinese and English databases, related to supplementation and replacement therapies of EH with anxiety or depression disorder, published from initial state to February 2021, will be collected in the form of computer retrieval. Two researchers will independently screen the literature, extracting data, assessing bias risk and assessing heterogeneity. We will use software WinBUGS 1.4. 3 and Stata 16.0 for pairwise meta-analysis and NMA to comprehensively evaluate various interventions. The quality of evidence will be evaluated through the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results This NMA will comprehensively compare and rank the efficacy and safety of a series of complementary and alternative therapies in treating EH with anxiety or depression disorder. Conclusion Supplementary and replacement therapies have accumulated rich experience of clinical practices in improving EH with anxiety or depression disorder. We expect that this NMA will guide practice and research by providing reliable evidence of evidence-based medicine for the treatment of EH with anxiety or depression disorder. Protocol registration number INPLASY202120068.
Anodal transcranial direct current stimulation increases corticospinal excitability, while performance is unchanged

Anodal transcranial direct current stimulation (a-tDCS) has been shown to improve bicycle time to fatigue (TTF) tasks at 70–80% of VO2max and downregulate rate of perceived exertion (RPE). This study aimed to investigate the effect of a-tDCS on a RPE-clamp test, a 250-kJ time trial (TT) and motor evoked potentials (MEP). Twenty participants volunteered for three trials; control, sham stimulation and a-tDCS. Transcranial magnetic stimulation was used to determine the corticospinal excitability for 12 participants pre and post sham stimulation and a-tDCS. The a-tDCS protocol consisted of 13 minutes of stimulation (2 mA) with the anode placed above the Cz. The RPE-clamp test consisted of 5 minutes ergometer bicycling at an RPE of 13 on the Borg scale, and the TT consisted of a 250 kJ (∼10 km) long bicycle ergometer test. During each test, power output, heart rate and oxygen consumption was measured, while RPE was evaluated. MEPs increased significantly by 36% (±36%) post a-tDCS, with 8.8% (±31%) post sham stimulation (p = 0.037). No significant changes were found for any parameter at the RPE-clamp or TT. The lack of improvement may be due to RPE being more controlled by afferent feedback during TT tests than during TTF tests. Based on the results of the present study, it is concluded that a-tDCS applied over Cz, does not enhance self-paced cycling performance.
Tumor Vasculature-Targeting Nanomedicines

Uncontrolled tumor growth and subsequent distant metastasis are highly dependent on an adequate nutrient supply from tumor blood vessels, which have relatively different pathophysiological characteristics from those of normal vasculature. Obviously, strategies targeting tumor vasculature, such as anti-angiogenic drugs and vascular disrupting agents, are attractive methods for cancer therapy. However, the off-target effects and high dose administration of these drug regimens critically restrict their clinical applications. In recent years, nanomedicines focused on tumor vasculature have been shown to be superior to traditional therapeutic methods and do not induce side effects. This review will first highlight the recent development of tumor vasculature-targeting nanomedicines from the following four aspects: 1) angiogenesis-inhibiting nanomedicines (AINs); 2) vasculature-disrupting nanomedicines (VDNs); 3) vasculature infarction nanomedicines (VINs); and 4) vasculature-regulating nanomedicines (VRNs). Furthermore, the design principles, limitations, and future directions are also discussed. STATEMENT OF SIGNIFICANCE: : Based on the essential roles of tumor blood vessels, the therapeutic strategies targeting tumor vasculature have exhibited good clinical therapeutic outcomes. However, poor patient adherence to free drug administration limits their clinical usage. Nanomedicines have great potential to overcome the abovementioned obstacle. This review summarizes the tumor-vasculature targeting nanomedicines from four aspects: 1) angiogenesis-inhibiting nanomedicines (AINs); 2) vasculature-disrupting nanomedicines (VDNs); 3) vasculature infarction nanomedicines (VINs); and 4) vasculature regulating nanomedicines (VRNs). In addition, this review provides perspectives on this research field.