Miracle-dz/UniFAR-FTUs huggingface dataset:
Participation of UV-regulated Genes in the Response to Helix-distorting DNA Damage in the Thermoacidophilic Crenarchaeon Sulfolobus acidocaldarius

Several species of Sulfolobales have been used as model organisms in the study of response mechanisms to ultraviolet (UV) irradiation in hyperthermophilic crenarchaea. To date, the transcriptional responses of genes involved in the initiation of DNA replication, transcriptional regulation, protein phosphorylation, and hypothetical function have been observed in Sulfolobales species after UV irradiation. However, due to the absence of knockout experiments, the functions of these genes under in situ UV irradiation have not yet been demonstrated. In the present study, we constructed five gene knockout strains (cdc6-2, tfb3, rio1, and two genes encoding the hypothetical proteins, Saci_0951 and Saci_1302) of Sulfolobus acidocaldarius and examined their sensitivities to UV irradiation. The knockout strains exhibited significant sensitivities to UV-B irradiation, indicating that the five UV-regulated genes play an important role in responses to UV irradiation in vivo. Furthermore, Δcdc6-2, Δrio1, ΔSaci_0951, and Δtfb3 were sensitive to a wide variety of helix-distorting DNA lesions, including UV-induced DNA damage, an intra-strand crosslink, and bulky adducts. These results reveal that cdc6-2, tfb3, rio1, and Saci_0951 are play more important roles in broad responses to helix-distorting DNA damage than in specific responses to UV irradiation.
Brevinin-GR23 from frog Hylarana guentheri with antimicrobial and antibiofilm activities against Staphylococcus aureus

ABSTRACT Brevinin-GR23 (B-GR23) was a brevinin-2 like antimicrobial peptide, which had antimicrobial activity against Staphylococcus aureus with minimum inhibitory concentration (MIC) of 16 μM. B-GR23 increased the bacterial membrane permeation, leading to the damage of membrane integrity and the leakage of genomic DNA, then causing the cell death. The peptide nearly inhibited all plantonic bacteria to start the initial attachment of biofilm at the concentration of 1 × MIC. Whereas the disruption rates on immature and mature biofilm decreased from 60% to 20%. B-GR23 reduced the production of extracellular polysaccharides (EPS) in the planktonic growth of S. aureus, which is a crucial structure of biofilm formation. B-GR23 with the concentration of ½ × MIC inhibited 50% water-soluble EPS, and 48% water-insoluble EPS, which contributed to the antibiofilm activity. B-GR23 had no significant toxicity to human blood cells under-tested concentration (200 μM), making it a potential template for designing antimicrobial peptides. Graphical abstract Brevinin-GR23, a stable antimicrobial and antibiofilm peptide against Staphylococcus aureus
3D-GIoU: 3D Generalized Intersection over Union for Object Detection in Point Cloud

Three-dimensional (3D) object detection is an important research in 3D computer vision with significant applications in many fields, such as automatic driving, robotics, and human–computer interaction. However, the low precision is an urgent problem in the field of 3D object detection. To solve it, we present a framework for 3D object detection in point cloud. To be specific, a designed Backbone Network is used to make fusion of low-level features and high-level features, which makes full use of various information advantages. Moreover, the two-dimensional (2D) Generalized Intersection over Union is extended to 3D use as part of the loss function in our framework. Empirical experiments of Car, Cyclist, and Pedestrian detection have been conducted respectively on the KITTI benchmark. Experimental results with average precision (AP) have shown the effectiveness of the proposed network.
Single-molecule localization microscopy as nonlinear inverse problem

Significance Single-molecule localization microscopy (SMLM) is quickly becoming an indispensable tool for studying biological structures. Meanwhile, we are presented with new challenges in the analyses of SMLM data arising from their unique noise statistics. In this paper, we solved a fundamental problem with regard to the modeling of SMLM data. Specifically, we established a theoretical connection between a set of experimentally acquired SMLM data and the underlying spatial distribution of fluorescent molecules. Based on this framework, we can extract higher-resolution information that is obscured by the raw data. The same framework also allows us to develop better image alignment algorithms, and thus obtain faster and more accurate results in particle fusion applications. We present a statistical framework to model the spatial distribution of molecules based on a single-molecule localization microscopy (SMLM) dataset. The latter consists of a collection of spatial coordinates and their associated uncertainties. We describe iterative parameter-estimation algorithms based on this framework, as well as a sampling algorithm to numerically evaluate the complete posterior distribution. We demonstrate that the inverse computation can be viewed as a type of image restoration process similar to the classical image deconvolution methods, except that it is performed on SMLM images. We further discuss an application of our statistical framework in the task of particle fusion using SMLM data. We show that the fusion algorithm based on our model outperforms the current state-of-the-art in terms of both accuracy and computational cost.
A Deactivation Factor of Fibrogenic Hepatic Stellate Cells Induces Regression of Liver Fibrosis in Mice

Hepatic stellate cells (HSCs), a key player in the progression of liver fibrosis, are activated by various inflammatory stimuli and converted to myofibroblast‐like cells with excessive collagen production. Despite many attempts to suppress activation of HSCs or inhibit collagen production in activated HSCs, their clinical applications have not been established yet. Recently, the deactivation of HSCs has been reported as a mechanism underlying the reversibility of experimental liver fibrosis. In the present study, we sought for deactivation factors of HSCs that induce regression of established liver fibrosis.
Positron Emission Tomography Can Support the Diagnosis of Dialysis-Related Amyloidosis

Background: The improvements in dialysis have not eliminated long-term problems, including dialysis-related amyloidosis (DRA), caused by Beta-2 microglobulin deposition. Several types of scintigraphy have been tested to detect DRA, none entered the clinical practice. Aim of the study was to assess the potential of PET-FDG scan in the diagnosis of DRA. Methods: Forty-six dialysis patients with at least one PET scan (72 scans) were selected out 162 patients treated in 2016–2018. Subjective global assessment (SGA), malnutrition inflammation score (A), Charlson Comorbidity Index (CCI), were assessed at time of scan; 218 age-matched cases with normal kidney function were selected as controls. PET scans were read in duplicate. Carpal tunnel syndrome was considered a proxy for DRA. A composite “amyloid score” score considered each dialysis year = 1 point; carpal tunnel-DRA = 5 points per site. Logistic regression, ROC curves and a prediction model were built. Results: The prevalence of positive PET was 43.5% in dialysis, 5% in controls (p < 0.0001). PET was positive in 14/15 (93.3%) scans in patients with carpal tunnel. PET sensitivity for detecting DRA was 95% (specificity 64%). Carpal tunnel was related to dialysis vintage and MIS. A positive PET scan was significantly associated with dialysis vintage, MIS and amyloid score. A prediction model to explain PET positivity combined clinical score and MIS, allowing for an AUC of 0.906 (CI: 0.813–0.962; p < 0.001). Conclusions: PET-FDG may identify DRA, and may be useful in detecting cases in which inflammation favours B2M deposition. This finding, needing large-scale confirmation, could open new perspectives in the study of DRA.
Unimanual and Bimanual Reach-and-Grasp Actions Can Be Decoded From Human EEG

While most tasks of daily life can be handled through a small number of different grasps, many tasks require the action of both hands. In these bimanual tasks, the second hand has either a supporting role (e.g. for fixating a jar) or a more active role (e.g. grasping a pot on both handles). In this study we attempt to discriminate the neural correlates of unimanual (performed with left and right hand) from bimanual reach-and-grasp actions using the low-frequency time-domain electroencephalogram (EEG). In a self-initiated movement task, 15 healthy participants were asked to perform unimanual (palmar and lateral grasps with left and right hand) and bimanual (double lateral, mixed palmar/lateral) reach-and-grasps on objects of daily life. Using EEG time-domain features in the frequency range of 0.3-3 Hz, we achieved multiclass-classification accuracies of 38.6 $\pm$ 6.6% (7 classes, 17.1% chance level) for a combination of 6 movements and 1 rest condition. The grand average confusion matrix shows highest true positive rates (TPR) for the rest (63%) condition while TPR for the movement classes varied between 33 to 41%. The underlying movement-related cortical potentials (MRCPs) show significant differences between unimanual (e.g left hand vs. right hand grasps) as well unimanual vs. bimanual conditions which both can be attributed to lateralization effects. We believe that these findings can be exploited and further used for attempts in providing persons with spinal cord injury a form of natural control for bimanual neuroprostheses.
Stem cell-based interventions for the prevention and treatment of germinal matrix-intraventricular haemorrhage in preterm infants.

BACKGROUND Germinal matrix-intraventricular haemorrhage (GMH-IVH) remains a substantial issue in neonatal intensive care units worldwide. Current therapies to prevent or treat GMH-IVH are limited. Stem cell-based therapies offer a potential therapeutic approach to repair, restore, and/or regenerate injured brain tissue. These preclinical findings have now culminated in ongoing human neonatal studies. OBJECTIVES To determine the benefits and harms of stem cell-based interventions for prevention or treatment of germinal matrix-intraventricular haemorrhage (GM-IVH) in preterm infants. SEARCH METHODS We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 1), in the Cochrane Library; MEDLINE via PubMed (1966 to 7 January 2019); Embase (1980 to 7 January 2019); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 7 January 2019). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA We attempted to identify randomised controlled trials, quasi-randomised controlled trials, and cluster trials comparing (1) stem cell-based interventions versus control; (2) mesenchymal stromal cells (MSCs) of type or source versus MSCs of other type or source; (3) stem cell-based interventions other than MSCs of type or source versus stem cell-based interventions other than MSCs of other type or source; or (4) MSCs versus stem cell-based interventions other than MSCs. For prevention studies, we included extremely preterm infants (less than 28 weeks' gestation), 24 hours of age or less, without ultrasound diagnosis of GM-IVH; for treatment studies, we included preterm infants (less than 37 weeks' gestation), of any postnatal age, with ultrasound diagnosis of GM-IVH. DATA COLLECTION AND ANALYSIS For each of the included trials, two review authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, type and source of MSCs, other stem cell-based interventions) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). Primary outcomes considered in this review are all-cause neonatal mortality, major neurodevelopmental disability, GM-IVH, and extension of pre-existing non-severe GM-IVH. We planned to use the GRADE approach to assess the quality of evidence. MAIN RESULTS Our search strategy yielded 769 references. We did not find any completed studies for inclusion. One randomised controlled trial is currently registered and ongoing. Five phase 1 trials are described in the excluded studies. AUTHORS' CONCLUSIONS Currently no evidence is available to show the benefits or harms of stem cell-based interventions for treatment or prevention of GM-IVH in preterm infants.
Stable Thiophosphate-based All-Solid-State Lithium Batteries through Conformally Interfacial Nano Coating.

All-solid-state lithium batteries (ASLBs) are promising for next generation energy storage system with critical safety. Among various candidates, thiophosphate-based electrolytes have shown great promises because of their high ionic conductivity. However, the narrow operation voltage and poor compatibility with high voltage cathode materials impede their application in the development of high energy ASLBs. In this work, we studied the failure mechanism of Li6PS5Cl at high voltage through in situ Raman spectra and investigated the stability with high-voltage LiNi1/3Mn1/3Co1/3O2 (NMC) cathode. With a facile wet chemical approach, we coated a thin layer of amorphous Li0.35La0. 5Sr0.05TiO3 (LLSTO) with 20 nm at the interface between NMC and Li6PS5Cl. We studied different coating parameters and optimized the coating thickness of the interface layers. Meanwhile, we studied the effect of NMC dimension to the ASLBs performance. We further performed the first principles thermodynamic calculations to understand the electrochemical stability between Li6PS5Cl and carbon, NMC, LLSTO, NMC/LLSTO. Attributed to the high stability of Li6PS5Cl with NMC/LLSTO and outstanding ionic conductivity of the interface layer and Li6PS5Cl, the electrochemical stability window of Li6PS5Cl was greatly improved to 4.0 V (vs. Li-In). At room temperature, the ASLB exhibit outstanding capacity of 107 mAh g-1 and keep stable for 420 cycles with a high capacity retention of 93.5 % at C/3.
RNA ligation precedes the retrotransposition of U6/LINE-1 chimeric RNA

Significance Long interspersed element-1s (L1s) encode 2 proteins (ORF1p and ORF2p) that preferentially mobilize (i.e., retrotranspose) their encoding messenger RNA (mRNA) transcript. ORF1p and/or ORF2p can also mobilize other cellular RNAs, including short interspersed elements (SINEs), U6 small nuclear RNA (snRNA), and mRNAs. Here, we demonstrate the RNA ligase RtcB can join U6 snRNA to L1 or other cellular RNAs to create chimeric RNAs; retrotransposition of the resultant chimeric RNAs leads to chimeric pseudogene formation; and chimeric U6/L1 RNAs are part of the transcriptome in multiple human cells. These data suggest RNA ligation contributes to the plasticity of the transcriptome and that the retrotransposition of chimeric RNAs can generate genetic variation in the human genome. Long interspersed element-1 (LINE-1 or L1) amplifies via retrotransposition. Active L1s encode 2 proteins (ORF1p and ORF2p) that bind their encoding transcript to promote retrotransposition in cis. The L1-encoded proteins also promote the retrotransposition of small-interspersed element RNAs, noncoding RNAs, and messenger RNAs in trans. Some L1-mediated retrotransposition events consist of a copy of U6 RNA conjoined to a variably 5′-truncated L1, but how U6/L1 chimeras are formed requires elucidation. Here, we report the following: The RNA ligase RtcB can join U6 RNAs ending in a 2′,3′-cyclic phosphate to L1 RNAs containing a 5′-OH in vitro; depletion of endogenous RtcB in HeLa cell extracts reduces U6/L1 RNA ligation efficiency; retrotransposition of U6/L1 RNAs leads to U6/L1 pseudogene formation; and a unique cohort of U6/L1 chimeric RNAs are present in multiple human cell lines. Thus, these data suggest that U6 small nuclear RNA (snRNA) and RtcB participate in the formation of chimeric RNAs and that retrotransposition of chimeric RNA contributes to interindividual genetic variation.
Molecular Basis of Cancer Pain Management: An Updated Review

Pain can have a significantly negative impact on the quality of life of patients. Therefore, patients may resort to analgesics to relieve the pain. The struggle to manage pain in cancer patients effectively and safely has long been an issue in medicine. Analgesics are the mainstay treatment for pain management as they act through various methods on the peripheral and central pain pathways. However, the variability in the patient genotypes may influence a drug response and adverse drug effects that follow through. This review summarizes the observed effects of analgesics on UDP-glucuronosyl (UGT) 2B7 isoenzyme, cytochrome P450 (CYP) 2D6, μ-opioid receptor μ 1 (OPRM1), efflux transporter P-glycoprotein (P-gp) and ATP-binding cassette B1 ABCB1/multiple drug resistance 1 (MDR1) polymorphisms on the mechanism of action of these drugs in managing pain in cancer. Furthermore, this review article also discusses the responses and adverse effects caused by analgesic drugs in cancer pain management, due to the inter-individual variability in their genomes.
Super-Resolution Reconstruction of Cell Pseudo-Color Image Based on Raman Technology

Raman spectroscopy visualization is a challenging task due to the interference of complex background noise and the number of selected measurement points. In this paper, a super-resolution image reconstruction algorithm for Raman spectroscopy is studied to convert raw Raman data into pseudo-color super-resolution imaging. Firstly, the Raman spectrum data of a single measurement point is measured multiple times to calculate the mean value to remove the random background noise, and innovatively introduce the Retinex algorithm and the median filtering algorithm which improve the signal-to-noise ratio. The novel method of using deep neural network performs a super-resolution reconstruction operation on the gray image. An adaptive guided filter that automatically adjusts the filter radius and penalty factor is proposed to highlight the contour of the cell, and the super-resolution reconstruction of the pseudo-color image of the Raman spectrum is realized. The average signal-to-noise ratio of the reconstructed pseudo-color image sub-band reaches 14.29 db, and the average value of information entropy reaches 4.30 db. The results show that the Raman-based cell pseudo-color image super-resolution reconstruction algorithm is an effective tool to effectively remove noise and high-resolution visualization. The contrast experiments show that the pseudo-color image Kullback–Leiber (KL) entropy of the color image obtained by the method is small, the boundary is obvious, and the noise is small, which provide technical support for the development of sophisticated single-cell imaging Raman spectroscopy instruments.
Hemokinin‐1 stimulates C‐C motif chemokine ligand 24 production in macrophages to enhance eosinophilic inflammation in nasal polyps

The mechanisms underlying mucosal eosinophilia in chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly clarified. The nervous system and neuropeptides play an important role in the regulation of immune response. Herein we explore the expression and function of hemokinin‐1 (HK‐1), a newly identified tachykinin, along with its receptor neurokinin 1 receptor (NK1R) in CRSwNP.
Population Pharmacokinetics of Doxycycline in Children

Doxycycline is a tetracycline-class antimicrobial labeled by the U.S. Food and Drug Administration for children >8 years of age for many common childhood infections. Doxycycline is not labeled for children ≤8 years of age, due to the association between tetracycline-class antibiotics and tooth staining, although doxycycline may be used off-label under severe conditions. ABSTRACT Doxycycline is a tetracycline-class antimicrobial labeled by the U.S. Food and Drug Administration for children >8 years of age for many common childhood infections. Doxycycline is not labeled for children ≤8 years of age, due to the association between tetracycline-class antibiotics and tooth staining, although doxycycline may be used off-label under severe conditions. Accordingly, there is a paucity of pharmacokinetic (PK) data to guide dosing in children 8 years and younger. We leveraged opportunistically collected plasma samples after intravenous (i.v.) and oral doxycycline doses received per standard of care to characterize the PK of doxycycline in children of different ages and evaluated the effect of obesity and fasting status on PK parameters. We developed a population PK model of doxycycline using data collected from 47 patients 0 to 18 years of age, including 14 participants ≤8 years. We developed a 1-compartment PK model and found doxycycline clearance to be 3.32 liters/h/70 kg of body weight and volume to be 96.8 liters/70 kg for all patients, comparable to values reported in adults. We estimated a bioavailability of 89.6%, also consistent with adult data. Allometrically scaled clearance and volume of distribution did not differ between children 2 to ≤8 years of age and children >8 to ≤18 years of age, suggesting that younger children may be given the same per-kilogram dosing. Obesity status and fasting status were not selected for inclusion in the final model. Additional doxycycline PK samples collected in future studies may be used to improve model performance and maximize its clinical value.
The Effect of Enteral Nutrition Support Rich in TGF-β in the Treatment of Inflammatory Bowel Disease in Childhood

Background and Objective: Malnutrition is a major complication of inflammatory bowel disease (IBD). Our aim of the study was to examine the effects of Modulen IBD supplementation, which was administered to IBD patients without limiting their daily diet in addition to medical treatment, on the clinical, laboratory, anthropometric values, and disease activities of these patients. Materials and Methods: Seventy three children with IBD were evaluated retrospectively. The cases were classified as those who had Crohn disease receiving (CD-M; n = 16) or not receiving Modulen IBD (CD; n = 19) and those who had ulcerative colitis receiving (UC-M; n = 13) or not receiving Modulen IBD (UC; n = 25). Disease activities, laboratory values, remission rates, and anthropometric measurements of the groups were compared. In addition to IBD treatment, Modulen IBD in which half of the daily calorie requirement was provided was given for eight weeks. Results: In the third month of treatment, 14 (88%) patients were in remission in CD-M group and eight (42%) patients were in remission in CD group. The height and weight z scores, which were low at the time of diagnosis, improved in the first week in CD-M group. Inflammatory parameters (UC) were significantly lower in the UC-M group compared to the UC group in first and third months. In the third month, eight (62%) patients in the UC-M group and four (16%) in the UC group were remitted clinically and in terms of laboratory values. Conclusions: TGF-β-rich enteral nutrition support in children with IBD is an easy, effective, and reliable approach. It was shown that TGF-β-rich enteral nutritional supplementation enabled the disease to enter the remission earlier, and contributed to the early recovery of weight and height scores.