Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling splicing outcome by combining 5′ss strength and splicing regulatory elements

Abstract Correct pre-mRNA processing in higher eukaryotes vastly depends on splice site recognition. Beyond conserved 5′ss and 3′ss motifs, splicing regulatory elements (SREs) play a pivotal role in this recognition process. Here, we present in silico designed sequences with arbitrary a priori prescribed splicing regulatory HEXplorer properties that can be concatenated to arbitrary length without changing their regulatory properties. We experimentally validated in silico predictions in a massively parallel splicing reporter assay on more than 3000 sequences and exemplarily identified some SRE binding proteins. Aiming at a unified ‘functional splice site strength’ encompassing both U1 snRNA complementarity and impact from neighboring SREs, we developed a novel RNA-seq based 5′ss usage landscape, mapping the competition of pairs of high confidence 5′ss and neighboring exonic GT sites along HBond and HEXplorer score coordinate axes on human fibroblast and endothelium transcriptome datasets. These RNA-seq data served as basis for a logistic 5′ss usage prediction model, which greatly improved discrimination between strong but unused exonic GT sites and annotated highly used 5′ss. Our 5′ss usage landscape offers a unified view on 5′ss and SRE neighborhood impact on splice site recognition, and may contribute to improved mutation assessment in human genetics.
Family structure in relation to body mass index and metabolic score in European children and adolescents

Living in single parent and blended families or as an only child—compared to living in two‐parent biological families or with siblings, respectively—is associated with a higher body mass index (BMI) in cross‐sectional studies. However, longitudinal research addressing the children's BMI in this context is scarce. Further, little is known about the association between family structure and metabolic health.
Draft Genome Sequence of Bacillus paralicheniformis Strain GSFE7, a Halotolerant Plant Growth-Promoting Bacterial Endophyte Isolated from Cultivated Saline Areas of the Dead Sea Region

Here, we report the draft genome sequence of Bacillus paralicheniformis strain GSFE7, which was isolated from saline fields near the Dead Sea region. The genome was 4,452,800 bp in size and contained 4,382 coding sequences. Several genes were predicted to be involved in auxin production, nitrogen fixation, phosphate mobilization, and putative production of siderophores and antibiotics such as bacitracin, butirosin, and fengycin. ABSTRACT Here, we report the draft genome sequence of Bacillus paralicheniformis strain GSFE7, which was isolated from saline fields near the Dead Sea region. The genome was 4,452,800 bp in size and contained 4,382 coding sequences. Several genes were predicted to be involved in auxin production, nitrogen fixation, phosphate mobilization, and putative production of siderophores and antibiotics such as bacitracin, butirosin, and fengycin.
Accurate identification of taxon‐specific molecular markers in plants based on DNA signature sequence

Accurate identification of plants remains a significant challenge for taxonomists and is the basis for plant diversity conservation. Although DNA barcoding methods are commonly used for plant identification, these are limited by the low amplification success and low discriminative power of selected genomic regions. In this study, we developed a k‐mer–based approach, the DNA signature sequence (DSS), to accurately identify plant taxon‐specific markers, especially at the species level. DSS is a constant‐length nucleotide sequence capable of identifying a taxon and distinguishing it from other taxa. In this study, we performed the first large‐scale study of DSS markers in plants. DSS candidates of 3899 angiosperm plant species were calculated based on a chloroplast data set with 4356 assemblies. Using Sanger sequencing of PCR amplicons and high‐throughput sequencing, DSSs were validated in four and 165 species, respectively. Based on this, the universality of the DSSs was over 79.38%. Several indicators influencing DSS marker identification and detection have also been evaluated, and common criteria for DSS application in plant identification have been proposed.
Valence bond solid state induced by impurity frustration in Cr 8 Ni

We provide a physically meaningful picture of the nature of the ground state of the Cr8Ni compound in the regime where it is a spin singlet. According to this picture, the anisotropy of the $Ni$ atom in the $Cr$ ring induces a dimerization in the molecule that makes the ground state to stabilize in a Valence Bond Solid phase of virtual spins. We characterize rigorously this phase by means of a particular non-local order parameter denoted the generalized string order parameter. In the completely antiferromagnetic regime, the system becomes frustrated. We have performed a numerical real-time evolution study of the correlations between the spin of the $Ni$ impurity and the rest of the spins in order to show the reaction of the system under this frustration. We provide results that manifestly show the agreement with the Valence Bond Solid picture introduced.
Muscle-Effort-Minimization-Inspired Kinematic Redundancy Resolution for Replicating Natural Posture of Human Arm

Replicating natural postures of human arms is essential to generate human-like behaviors in robotic applications for humans nearby. However, how to realize this requirement in interactive scenarios remains a challenge due to the kinematic redundancy and unknown postural control strategy of human arms. Inspired by the physiological characteristics that the musculoskeletal system is coordinated to minimize muscle effort in human behaviors, this paper aims to address the issue by solving a muscle effort minimization problem. It adopts a high-fidelity human arm musculoskeletal model (HAMM) and considers the implicit constraint (desired hand pose) and the inequality constraints (range of joint motion). The constrained minimization is in general nonconvex, consequently sensitive to initial guesses in iterative procedures. So, it is impracticable to solve it directly with existing gradient-based deterministic approaches or standard evolutionary algorithms. As the main contribution, a hybrid inverse kinematics algorithm was proposed for the HAMM with 7 independent and 13 mimic joints to obtain the feasible arm postures satisfying the minimization constraints. Using the arm swivel angle that parametrizes the kinematic redundancy of the HAMM, geometrically equidistant initial guess candidates can be generated over the 1-dimension feasible posture manifold. As another contribution, we present a two-phase global minimization algorithm to handle the nonconvexity of the constrained minimization. It consists of a local-search phase on the null-space of the geometric Jacobian matrix and a global-search phase with an initial guess resampling strategy. The proposed approach was validated by replicating the natural arm postures of 5 right-handed subjects in daily tasks.
Comparing biomechanical time series data across countermovement shrug loads

ABSTRACT The effect of load on time-series data has yet to be investigated during weightlifting derivatives. This study compared the effect of load on the force–time and velocity–time curves during the countermovement shrug (CMS). Twenty-nine males performed the CMS at relative loads of 40%, 60%, 80%, 100%, 120%, and 140% one repetition maximum (1RM) power clean (PC). A force plate measured the vertical ground reaction force (VGRF), which was used to calculate the barbell-lifter system velocity. Time-series data were normalized to 100% of the movement duration and assessed via statistical parametric mapping (SPM). SPM analysis showed greater negative velocity at heavier loads early in the unweighting phase (12–38% of the movement), and greater positive velocity at lower loads during the last 16% of the movement. Relative loads of 40% 1RM PC maximised propulsion velocity, whilst 140% 1RM maximized force. At higher loads, the braking and propulsive phases commence at an earlier percentage of the time-normalized movement, and the total absolute durations increase with load. It may be more appropriate to prescribe the CMS during a maximal strength mesocycle given the ability to use supramaximal loads. Future research should assess training at different loads on the effects of performance.
Targeting FAPα-expressing hepatic stellate cells overcomes resistance to antiangiogenics in colorectal cancer liver metastasis models

Vessel co-option has been demonstrated to mediate colorectal cancer liver metastasis (CRCLM) resistance to antiangiogenic therapy. The current mechanisms underlying vessel co-option have mainly focused on “hijacker” tumor cells, whereas the function of the “hijackee” sinusoidal blood vessels has not been explored. Here, we found that the occurrence of vessel co-option in bevacizumab-resistant CRCLM xenografts was associated with increased expression of fibroblast activation protein α (FAPα) in the co-opted hepatic stellate cells (HSCs), which was dramatically attenuated in HSC-specific conditional Fap-knockout mice bearing CRCLM allografts. Mechanistically, bevacizumab treatment induced hypoxia to upregulate the expression of fibroblast growth factor–binding protein 1 (FGFBP1) in tumor cells. Gain- or loss-of-function experiments revealed that the bevacizumab-resistant tumor cell–derived FGFBP1 induced FAPα expression by enhancing the paracrine FGF2/FGFR1/ERK1/-2/EGR1 signaling pathway in HSCs. FAPα promoted CXCL5 secretion in HSCs, which activated CXCR2 to promote the epithelial-mesenchymal transition of tumor cells and the recruitment of myeloid-derived suppressor cells. These findings were further validated in tumor tissues derived from patients with CRCLM. Targeting FAPα+ HSCs effectively disrupted the co-opted sinusoidal blood vessels and overcame bevacizumab resistance. Our study highlights the role of FAPα+ HSCs in vessel co-option and provides an effective strategy to overcome the vessel co-option–mediated bevacizumab resistance.
Flavobacterium litorale sp. nov., isolated from red alga.

A Gram-stain-negative and rod-shaped bacterial strain (WSW3-B6T) was isolated from red alga collected from the West Sea, Republic of Korea. Cells of strain WSW3-B6T were non-motile, aerobic and produced slightly yellow and mucoid colonies on marine agar. The strain grew optimally at 23-30 °C, with 0.5-4 % NaCl (w/v) and at pH 6.5-8.5. A phylogenetic analysis of the 16S rRNA gene revealed that strain WSW3-B6T belongs to the genus Flavobacterium within the family Flavobacteriaceae, having the highest sequence similarity to Flavobacterium arcticum SM1502T (96.7%), followed by Flavobacterium salilacus subsp. altitudinum LaA7.5T (96.2%) and Flavobacterium salilacus subsp. salilacus SaA2.12T (96.2%). The complete sequence of a circular chromosome of strain WSW3-B6T determined by combination of Oxford Nanopore and Illumina platforms comprised a total 2 725 095 bp with G+C content of 37.1 mol%. A comparative analysis based on the whole genome also showed the distinctiveness of strain WSW3-B6T. The average nucleotide identity (ANI) values between strain WSW3-B6T and the closest strains F. arcticum SM1502T, F. salilacus subsp. altitudinum LaA7.5T and F. salilacus subsp. salilacus SaA2.12T were 78.3, 77.8 and 77.7 %, respectively, while the digital DNA-DNA hybridization (dDDH) values between strain WSW3-B6T and the above closely related strains were 21.0, 20.4 and 20.3 %, respectively. Both the ANI and dDDH values supported the creation of a new species in the genus Flavobacterium. The major fatty acids (>10 %) were iso-C15 : 0 (19.3 %), C16 : 0 (14.0 %), iso-C17 : 0 3-OH (13.1 %) and C18 : 0 (10.7 %). The polar lipids of strain WSW3-B6T included phosphatidylethanolamine, three unidentified aminolipids and three unidentified lipids. Moreover, MK-6 was the only respiratory quinone. A comparison of the phylogenetic distinctiveness and the unique phenotypic and chemotaxonomic characteristics among strain WSW3-B6T and closely related type strains supported that strain WSW3-B6T (=KCTC 82708T=GDMCC 1.2627T) represents a novel species of the genus Flavobacterium, for which the name Flavobacterium litorale sp. nov. is proposed.
Public perceptions of urgency of severe cases of COVID-19 and inflammatory gastrointestinal disease

Background There is evidence that perceived urgency of medical complaints is associated with emergency care utilization. Patients’ perception of urgency can differ from physicians’ assessment. This study explored public perceptions of urgency of severe cases of COVID-19 and inflammatory gastrointestinal disease and analyzed variations in perceptions of urgency by characteristics of the afflicted person in the vignettes and sociodemographic characteristics of respondents. Methods Vignettes with severe symptoms of either inflammatory gastrointestinal disease or COVID-19 with comparable urgency of treatment were used in a telephone survey in Germany (N = 1,207). Besides disease, the vignettes varied in terms of sex, age (child, middle-aged person, old person) and daytime (Tuesday morning, Tuesday evening). Respondents were asked to rate the urgency of the reported symptoms with four items. A sum scale was computed. Variations in perceptions of urgency according to vignette characteristics and sociodemographic characteristics of the respondents (sex, age, educational level, migration background, children (yes/no) and personal affliction) were analyzed using a linear regression model. Results In terms of vignette characteristics, multivariate analysis showed a lower estimated urgency for males, as well as for the middle-aged and aged persons, compared to the child vignettes, and for COVID-19, compared to inflammatory gastrointestinal disease. Regarding the characteristics of the respondents, estimated urgency increased with age and was lower among respondents, who were previously affected by the symptoms themselves. Conclusion Although urgency in the vignettes was comparable, variations in estimated urgency by age and sex of the afflicted person and the described disease as well as age and personal affliction of the respondents were identified. This could result in an inadequate health care service utilization. Therefore, variations in public perceptions of urgency should be considered in the planning of public campaigns on adequate health care services utilization.
Nonlinear point-process estimation of neural spiking activity based on variational Bayesian inference

Objective. Understanding neural encoding and decoding processes are crucial to the development of brain-machine interfaces (BMI). Higher decoding speed of neural signals is required for the large-scale neural data and the extremely low detection delay of closed-loop feedback experiment. Approach. To achieve higher neural decoding speed, we proposed a novel adaptive higher-order nonlinear point-process filter based on the variational Bayesian inference (VBI) framework, called the HON-VBI. This algorithm avoids the complex Monte Carlo random sampling in the traditional method. Using the VBI method, it can quickly implement inferences of state posterior distribution and the tuning parameters. Main results. Our result demonstrates the effectiveness and advantages of the HON-VBI by application for decoding the multichannel neural spike trains of the simulation data and real data. Compared with traditional methods, the HON-VBI greatly reduces the decoding time of large-scale neural spike trains. Through capturing the nonlinear evolution of system state and accurate estimating of time-varying tuning parameters, the decoding accuracy is improved. Significance. Our work can be applied to rapidly decode large-scale multichannel neural spike trains in BMIs.
Genomic analyses of wild argali, domestic sheep, and their hybrids provide insights into chromosome evolution, phenotypic variation, and germplasm innovation

Understanding the genetic mechanisms of phenotypic variation in hybrids between domestic animals and their wild relatives may aid germplasm innovation. Here, we report the high-quality genome assemblies of a male Pamir argali (O. ammon polii, 2n = 56), a female Tibetan sheep (O. aries, 2n = 54), and a male hybrid of Pamir argali and domestic sheep, and the high-throughput sequencing of 425 ovine animals, including the hybrids of argali and domestic sheep. We detected genomic synteny between Chromosome 2 of sheep and two acrocentric chromosomes of argali. We revealed consistent satellite repeats around the chromosome breakpoints, which could have resulted in chromosome fusion. We observed many more hybrids with karyotype 2n = 54 than with 2n = 55, which could be explained by the selfish centromeres, the possible decreased rate of normal/balanced sperm, and the increased incidence of early pregnancy loss in the aneuploid ewes or rams. We identified genes and variants associated with important morphological and production traits (e.g., body weight, cannon circumference, hip height, and tail length) that show significant variations. We revealed a strong selective signature at the mutation (c.334C > A, p.G112W) in TBXT and confirmed its association with tail length among sheep populations of wide geographic and genetic origins. We produced an intercross population of 110 F2 offspring with varied number of vertebrae and validated the causal mutation by whole-genome association analysis. We verified its function using CRISPR-Cas9 genome editing. Our results provide insights into chromosomal speciation and phenotypic evolution and a foundation of genetic variants for the breeding of sheep and other animals.
Resistance of mitochondrial DNA to cadmium and Aflatoxin B1 damage-induced germline mutation accumulation in C. elegans

Abstract Mitochondrial DNA (mtDNA) is prone to mutation in aging and over evolutionary time, yet the processes that regulate the accumulation of de novo mtDNA mutations and modulate mtDNA heteroplasmy are not fully elucidated. Mitochondria lack certain DNA repair processes, which could contribute to polymerase error-induced mutations and increase susceptibility to chemical-induced mtDNA mutagenesis. We conducted error-corrected, ultra-sensitive Duplex Sequencing to investigate the effects of two known nuclear genome mutagens, cadmium and Aflatoxin B1, on germline mtDNA mutagenesis in Caenorhabditis elegans. Detection of thousands of mtDNA mutations revealed pervasive heteroplasmy in C. elegans and that mtDNA mutagenesis is dominated by C:G → A:T mutations generally attributed to oxidative damage. However, there was no effect of either exposure on mtDNA mutation frequency, spectrum, or trinucleotide context signature despite a significant increase in nuclear mutation rate after aflatoxin B1 exposure. Mitophagy-deficient mutants pink-1 and dct-1 accumulated significantly higher levels of mtDNA damage compared to wild-type C. elegans after exposures. However, there were only small differences in mtDNA mutation frequency, spectrum, or trinucleotide context signature compared to wild-type after 3050 generations, across all treatments. These findings suggest mitochondria harbor additional previously uncharacterized mechanisms that regulate mtDNA mutational processes across generations.
Predicting demographic characteristics from anterior segment OCT images with deep learning: A study protocol

Introduction Anterior segment optical coherence tomography (AS-OCT) is a non-contact, rapid, and high-resolution in vivo modality for imaging of the eyeball’s anterior segment structures. Because progressive anterior segment deformation is a hallmark of certain eye diseases such as angle-closure glaucoma, identification of AS-OCT structural changes over time is fundamental to their diagnosis and monitoring. Detection of pathologic damage, however, relies on the ability to differentiate it from normal, age-related structural changes. Methods and analysis This proposed large-scale, retrospective cross-sectional study will determine whether demographic characteristics including age can be predicted from deep learning analysis of AS-OCT images; it will also assess the importance of specific anterior segment areas of the eyeball to the prediction. We plan to extract, from SUPREME®, a clinical data warehouse (CDW) of Seoul National University Hospital (SNUH; Seoul, South Korea), a list of patients (at least 2,000) who underwent AS-OCT imaging between 2008 and 2020. AS-OCT images as well as demographic characteristics including age, gender, height, weight and body mass index (BMI) will be collected from electronic medical records (EMRs). The dataset of horizontal AS-OCT images will be split into training (80%), validation (10%), and test (10%) datasets, and a Vision Transformer (ViT) model will be built to predict demographics. Gradient-weighted Class Activation Mapping (Grad-CAM) will be used to visualize the regions of AS-OCT images that contributed to the model’s decisions. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (AUC) will be applied to evaluate the model performance. Conclusion This paper presents a study protocol for prediction of demographic characteristics from AS-OCT images of the eyeball using a deep learning model. The results of this study will aid clinicians in understanding and identifying age-related structural changes and other demographics-based structural differences. Trial registration Registration ID with open science framework: 10.17605/OSF.IO/FQ46X.
Efficacy and safety of chemotherapy regimens for first-line treatment of advanced esophageal squamous cell carcinoma in Asia: a systematic review

ABSTRACT Introduction There is no consensus on the optimal palliative first-line chemotherapy regimen for East Asian patients with advanced esophageal squamous cell carcinoma (ESCC). Areas covered We conducted a systematic review using a literature search of PubMed, Embase, and the Cochrane Library without date restrictions, and abstracts from major oncology congresses. Studies meeting the following criteria were included: East Asian patients ≥18 years old with metastatic/locally advanced unresectable ESCC; first-line chemotherapy; reporting of overall survival, progression-free survival, duration of response, overall response rate, and/or safety; randomized controlled trials, non-randomized controlled trials, and prospective or retrospective comparative studies. In total, 39 articles were identified for: platinum plus fluoropyrimidine (n = 9), platinum plus taxane (n = 16), platinum plus fluoropyrimidine plus taxane (n = 7), platinum plus fluoropyrimidine plus other (n = 3), irinotecan plus platinum (n = 2), taxane plus fluoropyrimidine (n = 1). Expert opinion The available data supports both taxane plus platinum regimens and fluoropyrimidine plus platinum regimens in the first-line treatment of East Asian patients with ESCC. Compared with data from doublet chemotherapy studies, triplet chemotherapy appeared to improve ORR, but did not seem to prolong OS, possibly due to an increased incidence of adverse events.