Miracle-dz/UniFAR-FTUs huggingface dataset:
Canonical correlation analysis for multi-omics: Application to cross-cohort analysis

Integrative approaches that simultaneously model multi-omics data have gained increasing popularity because they provide holistic system biology views of multiple or all components in a biological system of interest. Canonical correlation analysis (CCA) is a correlation-based integrative method designed to extract latent features shared between multiple assays by finding the linear combinations of features–referred to as canonical variables (CVs)–within each assay that achieve maximal across-assay correlation. Although widely acknowledged as a powerful approach for multi-omics data, CCA has not been systematically applied to multi-omics data in large cohort studies, which has only recently become available. Here, we adapted sparse multiple CCA (SMCCA), a widely-used derivative of CCA, to proteomics and methylomics data from the Multi-Ethnic Study of Atherosclerosis (MESA) and Jackson Heart Study (JHS). To tackle challenges encountered when applying SMCCA to MESA and JHS, our adaptations include the incorporation of the Gram-Schmidt (GS) algorithm with SMCCA to improve orthogonality among CVs, and the development of Sparse Supervised Multiple CCA (SSMCCA) to allow supervised integration analysis for more than two assays. Effective application of SMCCA to the two real datasets reveals important findings. Applying our SMCCA-GS to MESA and JHS, we identified strong associations between blood cell counts and protein abundance, suggesting that adjustment of blood cell composition should be considered in protein-based association studies. Importantly, CVs obtained from two independent cohorts also demonstrate transferability across the cohorts. For example, proteomic CVs learned from JHS, when transferred to MESA, explain similar amounts of blood cell count phenotypic variance in MESA, explaining 39.0% ~ 50.0% variation in JHS and 38.9% ~ 49.1% in MESA. Similar transferability was observed for other omics-CV-trait pairs. This suggests that biologically meaningful and cohort-agnostic variation is captured by CVs. We anticipate that applying our SMCCA-GS and SSMCCA on various cohorts would help identify cohort-agnostic biologically meaningful relationships between multi-omics data and phenotypic traits.
Nontriplet feature of genetic code in Euplotes ciliates is a result of neutral evolution

Significance In this work, we provide compelling evidence that Euplotes genetic code violates the triplet nature of the genetic decoding that was thought to be universal. Thus, Euplotes possess the most extreme example of genetic code variation described so far. The nontriplecy arises from abundant ribosomal frameshift sites with no regulatory function, where stop-codons distant from the 3′ transcript end specify +1 or +2 ribosomal frameshifting with high accuracy. We show that this violation of the triplet coding in Euplotes is brought about and further maintained by neutral evolution rather than selective processes but still is irreversible.
Mathematical tasks, study approaches, and course grades in undergraduate mathematics: a year-by-year analysis

Students approach learning in different ways, depending on the experienced learning situation. A deep approach is geared toward long-term retention and conceptual change while a surface approach focuses on quickly acquiring knowledge for immediate use. These approaches ultimately affect the students’ academic outcomes. This study takes a cross-sectional look at the approaches to learning used by students from courses across all four years of undergraduate mathematics and analyses how these relate to the students’ grades. We find that deep learning correlates with grade in the first year and not in the upper years. Surficial learning has no correlation with grades in the first year and a strong negative correlation with grades in the upper years. Using Bloom's taxonomy, we argue that the nature of the tasks given to students is fundamentally different in lower and upper year courses. We find that first-year courses emphasize tasks that require only low-level cognitive processes. Upper year courses require higher level processes but, surprisingly, have a simultaneous greater emphasis on recall and understanding. These observations explain the differences in correlations between approaches to learning and course grades. We conclude with some concerns about the disconnect between first year and upper year mathematics courses and the effect this may have on students.
Postoperative surgical complications after pediatric kidney transplantation in low weight recipients (<15 kg): a systematic review

Purpose of review Kidney transplantation in low-weight recipients (<15 kg) is a challenging surgery with special characteristics. We proposed to perform a systematic review to determine the postoperative complication rate and the type of complications after kidney transplantation in low-weight recipients (<15 kg). The secondary objectives were to determine graft survival, functional outcomes, and patient survival after kidney transplantation in low-weight recipients. Methods A systematic review was performed according to preferred reporting items for systematic reviews and meta-analyses. Medline and Embase databases were searched to identify all studies reporting outcomes on kidney transplantation in low-weight recipients (<15 kg). Results A total of 1254 patients in 23 studies were included. The median postoperative complications rate was 20.0%, while 87.5% of those were major complications (Clavien ≥3). Further, urological and vascular complications rates were 6.3% (2.0–11.9) and 5.0% (3.0–10.0), whereas the rate of venous thrombosis ranged from 0 to 5.6%. Median 10-year graft and patient survival were 76 and 91.0%. Summary Kidney transplantation in low-weight recipients is a challenging procedure complicated by a high rate of morbidity. Finally, pediatric kidney transplantation should be performed in centers with expertise and multidisciplinary pediatric teams.
Amisulpride as a potential disease‐modifying drug in the treatment of tauopathies

Hyperphosphorylation and aggregation of the microtubule‐associated protein tau cause the development of tauopathies, such as Alzheimer's disease and frontotemporal dementia (FTD). We recently uncovered a causal link between constitutive serotonin receptor 7 (5‐HT7R) activity and pathological tau aggregation. Here, we evaluated 5‐HT7R inverse agonists as novel drugs in the treatment of tauopathies.
RETICULON-LIKE PROTEIN B2 is a proviral factor co-opted for the biogenesis of viral replication organelles in plants

Abstract Endomembrane remodeling to form a viral replication complex (VRC) is crucial for a virus to establish infection in a host. Although the composition and function of VRCs have been intensively studied, host factors involved in the assembly of VRCs for plant RNA viruses have not been fully explored. TurboID-based proximity labeling (PL) has emerged as a robust tool for probing molecular interactions in planta. However, few studies have employed the TurboID-based PL technique for investigating plant virus replication. Here, we used Beet black scorch virus (BBSV), an endoplasmic reticulum (ER)–replicating virus, as a model and systematically investigated the composition of BBSV VRCs in Nicotiana benthamiana by fusing the TurboID enzyme to viral replication protein p23. Among the 185 identified p23-proximal proteins, the reticulon family of proteins showed high reproducibility in the mass spectrometry data sets. We focused on RETICULON-LIKE PROTEIN B2 (RTNLB2) and demonstrated its proviral functions in BBSV replication. We showed that RTNLB2 binds to p23, induces ER membrane curvature, and constricts ER tubules to facilitate the assembly of BBSV VRCs. Our comprehensive proximal interactome analysis of BBSV VRCs provides a resource for understanding plant viral replication and offers additional insights into the formation of membrane scaffolds for viral RNA synthesis.
Extremal problems on graphs, directed graphs and hypergraphs

This thesis is concerned with extremal problems on graphs and similar structures. We first study degree conditions in uniform hypergraphs that force matchings of various sizes. Our main result in this area improves bounds of Markstrom and Rucinski on the minimum d-degree which forces a perfect matching in a k-uniform hypergraph on n vertices. We then study connectivity conditions in tournaments that ensure the existence of partitions of the vertex set that satisfy various properties. In 1982 Thomassen asked whether every sufficiently strongly connected tournament T admits a partition of its vertex set into t vertex classes such that the subtournament induced on T by each class is strongly k-connected. Our main result in this area implies an affirmative answer to this question. Finally we investigate the typical structure of graphs and directed graphs with some forbidden subgraphs. We answer a question of Cherlin by finding the typical structure of triangle-free oriented graphs. Moreover, our results generalise to forbidden transitive tournaments and forbidden oriented cycles of any order, and also apply to digraphs. We also determine, for all k>5, the typical structure of graphs that do not contain an induced 2k-cycle. This verifies a conjecture of Balogh and Butterfield.
Gene and protein expression and metabolic flux analysis reveals metabolic scaling in liver ex vivo and in vivo

Metabolic scaling, the inverse correlation of metabolic rates to body mass, has been appreciated for more than 80 years. Studies of metabolic scaling have largely been restricted to mathematical modeling of caloric intake and oxygen consumption, and mostly rely on computational modeling. The possibility that other metabolic processes scale with body size has not been comprehensively studied. To address this gap in knowledge, we employed a systems approach including transcriptomics, proteomics, and measurement of in vitro and in vivo metabolic fluxes. Gene expression in livers of five species spanning a 30,000-fold range in mass revealed differential expression according to body mass of genes related to cytosolic and mitochondrial metabolic processes, and to detoxication of oxidative damage. To determine whether flux through key metabolic pathways is ordered inversely to body size, we applied stable isotope tracer methodology to study multiple cellular compartments, tissues, and species. Comparing C57BL/6 J mice with Sprague-Dawley rats, we demonstrate that while ordering of metabolic fluxes is not observed in in vitro cell-autonomous settings, it is present in liver slices and in vivo. Together, these data reveal that metabolic scaling extends beyond oxygen consumption to other aspects of metabolism, and is regulated at the level of gene and protein expression, enzyme activity, and substrate supply.
Vascularized adipose tissue engineering: moving towards soft tissue reconstruction

Soft tissue defects are a common clinical challenge mostly caused by trauma, congenital anomalies and oncological surgery. Current soft tissue reconstruction options include synthetic materials (fillers and implants) and autologous adipose tissue transplantation through flap surgery and/or lipotransfer. Both reconstructive options hold important disadvantages to which vascularized adipose tissue engineering (VATE) strategies could offer solutions. In this review, we first summarized pivotal characteristics of functional adipose tissue such as the structure, function, cell types, development and extracellular matrix (ECM). Next, we discussed relevant cell sources and how they are applied in different state-of-the-art VATE techniques. Herein, biomaterial scaffolds and hydrogels, ECMs, spheroids, organoids, cell sheets, three dimensional printing and microfluidics are overviewed. Also, we included extracellular vesicles and emphasized their potential role in VATE. Lastly, current challenges and future perspectives in VATE are pointed out to help to pave the road towards clinical applications.
The timing of non-thermal soft X-ray emission line broadenings in solar flares

We study 59 solar limb flares using the Bragg Crystal Spectrometer (BCS) on Yohkoh and the Burst and Transient Source Experiment (BATSE) to investigate the relative timings between the Hard X-Ray (HXR) emission and the observed non-thermal broadenings of X-ray emission lines (Vnt). We show that the duration of the HXR flux rise to maximum emission aects the relative timing of the main Vnt peak with respect to the main HXR peak. In20% of the flares studied, secondary peaks in Vnt are observed. These are always associated with a strong HXR pulse and usually occur after the associated HXR pulse. There are also flares that show a relationship between the decay times of Vnt and HXR flux. These results are conducive to a causal relationship between the HXR flux and Vnt. We divided the sample of flares into two classes, gradual rise and impulsive rise, depending on the shape of the HXR lightcurve up to maximum emission. We show that the Vnt behaviour diers in the two classes. The implications are discussed with a view to understanding the mechanism of Vnt generation.
Excitonic solar cells based on van der Waals heterojunctions of Janus III–VI chalcogenide monolayers

We construct the two-dimensional (2D) excitonic solar cells based on type II vdW heterojunctions of Janus III–VI chalcogenide monolayers and investigate the performance of the device using the first principle. The calculated solar energy absorbance of In2SSe/GaInSe2 and In2SeTe/GaInSe2 heterojunctions is the order of 105 cm−1. The predicted photoelectric conversion efficiency of the In2SeTe/GaInSe2 heterojunction can reach up to 24.5%, which compares favorably with other previously studied 2D heterojunctions. The excellent performance of In2SeTe/GaInSe2 heterojunction originates from the fact that the built-in electric field at the interface of In2SeTe/GaInSe2 promote the flow of the photogenerated electrons. The results suggest that 2D Janus Group-III chalcogenide heterojunction can be a good candidate for new optoelectronic nanodevices.
Probing differences among Aβ oligomers with two triangular trimers derived from Aβ

Significance Oligomers of the β-amyloid peptide (Aβ) contribute to neurodegeneration in Alzheimer’s disease and are promising targets for therapies against Alzheimer’s disease. Understanding the structures and biology of Aβ oligomers is important for understanding the molecular basis of Alzheimer’s disease and for developing better therapeutics and diagnostics for the disease. Aβ oligomers are difficult to study because they are heterogeneous and unstable. To gain insights into Aβ oligomers and their role in neurodegeneration, we create, characterize, and compare two different well-defined chemical models of Aβ oligomers composed of different peptide fragments from Aβ that are constrained into β-hairpin conformations.
Management of dialysis patients with hepatitis C virus in the era of direct‐acting antiviral therapy

The clinical use of direct‐acting antivirals (DAAs) for hepatitis C virus (HCV) infection has dramatically changed management of patients with HCV liver disease since 2014; this is also true for patients undergoing dialysis. Due to the high tolerability and antiviral efficacy of anti‐HCV therapy, most dialysis patients with HCV infection should currently be candidates for this treatment. Many patients with HCV antibodies no longer have HCV infection, and it is difficult to identify patients with actual HCV infection based only on HCV antibody assays. Despite the high rate of successful HCV eradication, the risk of liver‐related events such as hepatocellular carcinoma (HCC), the major complication of HCV infection, persists even after HCV cure, and patients at risk of HCC should undergo continuous HCC surveillance. Finally, the rarity of HCV reinfection and the survival benefit of HCV eradication in dialysis patients should be explored in further studies.
In silico exploration of antioxidants as oxidation protectant for PITRM1 peptidase activity, an Alzheimer disease target

To find efficient antioxidants to protect oxidation prone cysteine residues of the peptidase PITRM1 using molecular docking and simulation techniques. A total of 50 antioxidants were docked with PITRM1 at the oxidation prone region Cys89 and Cys96 using Autodock Vina software. The lowest socred compounds were predicted for its Blood brain barrier permeability using LightBBB. Molecular dynamic simulations of the PITRM1 and Ascorbic acid/Silymarin complex were performed using the GROMACS 2020.1 package and the free energy calculations were performed using gmx_MMPBSA. The RMSD, RMSF, Rg, Minimum distance and Hydrogen bonds were also evaluated. Silymarin, Ascorbic acid, Naringenin, Gallic acid, Chlorogenic acid, Rosmarinic acid, (‐)‐Epicatechin, Genistein showed a docking score of above –5.3 kcal/mol. Silymarin and Ascorbic acid were predicted to cross the Blood Brain Barrier. Molecular dynamic simulation and mmPBSA analysis revealed that Silymarin showed a positive free energy implying no affinity to PITRM1 and ascorbic acid has low ΔG with –13.13 kJ/mol. The stability of the ascorbic acid complex was high (RMSD: 0.160 ± 0.018 nm, Minimum Distance: 0.163 ± 0.001 nm and four hydrogen bonds) and fluctuation induced due to ascorbic acid was low. Ascorbic acid was found to effectively interact with the cysteine oxidation prone region and can have a potential role in reducing the oxidised cysteine in PITRM1 to modulate its peptidase activity.
Isolation and Characterization of a Weizmannia coagulans Bacteriophage Youna2 and Its Endolysin PlyYouna2

Weizmannia coagulans (formerly Bacillus coagulans) is Gram-positive, and spore-forming bacteria causing food spoilage, especially in acidic canned food products. To control W. coagulans, we isolated a bacteriophage Youna2 from a sewage sludge sample. Morphological analysis revealed that phage Youna2 belongs to the Siphoviridae family with a non-contractile and flexible tail. Youna2 has 52,903 bp double-stranded DNA containing 61 open reading frames. There are no lysogeny-related genes, suggesting that Youna2 is a virulent phage. plyYouna2, a putative endolysin gene was identified in the genome of Youna2 and predicted to be composed of a N-acetylmuramoyl-L-alanine amidase domain (PF01520) at the N-terminus and unknown function DUF5776 domain (PF19087) at the C-terminus. While phage Youna2 has a narrow host range, infecting only certain strains of W. coagulans, PlyYouna2 exhibited a broad antimicrobial spectrum beyond the Bacillus genus. Interestingly, PlyYouna2 can lyse Gram-negative bacteria such as Escherichia coli, Yersinia enterocolitica, Pseudomonas putida and Cronobacter sakazakii without other additives to destabilize bacterial outer membrane. To the best of our knowledge, Youna2 is the first W. coagulans-infecting phage and we speculate its endolysin PlyYouna2 can provide the basis for the development of a novel biocontrol agent against various foodborne pathogens.
An Adaptive Variable Structure Control Approach for Mobile Robots

This paper addresses the robust tracking of mobile robots with uncertain parameter variations. Based on the fact that a controllable driftless system with \%m\% inputs and at most \%m+2\% state variables is a differentially flat system, we develop a robust control approach to the trajectory tracking problem of a three wheel mobile robot via the dynamical extension approach and adaptive variable structure control technique. By applying the dynamical extension approach to the kinematic model of the three wheel mobile robot, the exact linearization of the extended dynamic feedback system is first realized under mild regular condition. In designing the robust control law we adopt the control interpolation in a boundary layer and on line parameter estimation to avoid the control chattering under large parameter uncertainties. Finally, numerical simulations are performed to show the efficiency of the proposed approach.
Optimization approach for tube circuit of fin-and-tube heat exchanger based on genetic algorithm

A novel tube circuit optimization approach for fin-and-tube heat exchanger was presented by developing a particular genetic coding method and genetic operators.A case study was performed on a practical heat exchanger.The optimization objective of the case was to obtain the shortest joint tube length of the tube circuit with the constraint conditions of satisfying the designed heat exchange capacity and the convenience of manufacture.Optimization result showed that the designed algorithm could converge within 5 h and the total joint tube length decreased by 25% after optimization.
DMD Gene and Dystrophinopathy Phenotypes Associated With Mutations: A Systematic Review for Clinicians

Abstract The diagnosis of Duchenne and Becker muscular dystrophy (DBMD) is made by genetic testing in approximately 95% of cases. Although specific mutations can be associated with skeletal muscle phenotype, pulmonary and cardiac comorbidities (leading causes of death in Duchenne) have not been associated with Duchenne muscular dystrophy mutation type or location and vary within families. Therefore, identifying predictors for phenotype severity beyond frameshift prediction is important clinically. We performed a systematic review assessing research related to genotype–phenotype correlations in DBMD. While there are severity differences across the spectrum and within mild and severe forms of DBMD, few protective or exacerbating mutations within the dystrophin gene were reported. Except for intellectual disability, clinical test results reporting genotypic information are insufficient for clinical prediction of severity and comorbidities and the predictive validity is too low to be useful when advising families. Including expanded information coupled with proposed severity predictions in clinical genetic reports for DBMD is critical for improving anticipatory guidance.
A ROS-response hyaluronic acid-coated/chitosan polymer prodrug for enhanced tumour targeting efficacy of SN38

Abstract Ethyl-10-hydroxycamptothecin (SN38) is a camptothecin derivative with significant anti-tumour therapeutic potential, while the clinical application of SN38 was limited by its poor water solubility and low stability. Herein, a core-shell polymer prodrug hyaluronic acid @chitosan-S-SN38 (HA@CS-S-SN38) was designed by CS-S-SN38 as the core and the HA as the shell, which aims to overcome the limitations of the clinical application of SN38, while realising the high tumour targeting of polymer prodrug and the controllable release of drug in tumour cells. HA@CS-S-SN38 showed the high responsiveness of the tumour microenvironment and the safe stability of blood circulation. Furthermore, HA@CS-S-SN38 exhibited the begin uptake efficiency and favourable apoptosis in the 4T1 cells. More importantly, compared with irinotecan hydrochloride trihydrate (CPT-11), HA@CS-S-SN38 significantly improved the conversion efficiency of the prodrug to SN38, and showed excellent tumour targeting and retention in vivo by combining passive and active targeting strategies. In tumour-bearing mice treatment, HA@CS-S-SN38 showed the perfect anti-tumour effect and therapeutic safety. These results indicated that the polymer prodrug designed by ROS-response/HA-modification strategy is a safe and efficient drug delivery system, which provides a new idea for clinical utilisation of SN38 and warrants further evaluation.
A Generic Set-Based Particle Swarm Optimization Algorithm

Several set-based particle swarm optimization algorithms have been proposed in the literature for solving discrete and combinatorial optimization problems. However, a simple but generic algorithm defined in terms of mathematical sets is still missing. In this paper a new algorithm called Set-Based PSO is proposed that fills this gap. The Multidimensional Knapsack Problem is used as a test problem to investigate the performance of the algorithm. Computational experiments are presented on a set of problems known from the literature both for parameter tuning and to compare the algorithm’s performance to that of two alternative algorithms.