Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-wide DNA methylation patterns in monocytes derived from patients with primary Sjogren syndrome

Supplemental Digital Content is available in the text Abstract Background: Epigenetics, especially DNA methylation, plays an important role in the pathogenesis of primary Sjogren syndrome (pSS). Our study aimed to reveal the role of DNA methylation in peripheral monocytes of pSS patients. Methods: A total of 11 pSS patients and five age-matched healthy controls (HCs) were included in this study. Monocytes were isolated from peripheral blood mononuclear cells using magnetic microbeads. DNA methylation profiles were generated using Human Methylation 850K BeadChips. Results: In monocytes from pSS patients, we identified 2819 differentially methylated positions (DMPs), comprising 1977 hypomethylated- and 842 hypermethylated-DMPs, corresponding to 1313 unique genes when compared with HCs. IFI44L, MX1, PAARP9, and IFITM1, which influence the interferon (IFN) signaling pathway, were among the genes hypomethylated in pSS. Functional analysis of genes with a minimum of two DMPs showed involvement in antigen binding, transcriptional regulation, cell adhesion, IFN-γ pathway, type I IFN pathway, antigen presentation, Epstein-Barr virus infection, human T-lymphotropic virus type 1 virus infection, and metabolic disease-related pathways. In addition, patients with higher serum IgG levels exhibited enrichment in Notch signaling and metabolic-related pathways. Upon comparing monocytes with salivary gland epithelial cells, an important overlap was observed in the cell cycle, cell senescence, and interleukin-17 signaling pathways. The differentially methylated genes were more enriched in the ribosome- and AMP-activated protein kinase signaling pathway in anti-Ro/SSA and anti-La/SSB autoantibodies double-positive patients. Conclusion: Genome-wide DNA methylation profiling revealed significant differences in DNA methylation in monocytes isolated from patients with pSS.
Host cystathionine-γ lyase derived hydrogen sulfide protects against Pseudomonas aeruginosa sepsis

Hydrogen sulfide (H2S) has recently been recognized as a novel gaseous transmitter with several anti-inflammatory properties. The role of host- derived H2S in infections by Pseudomonas aeruginosa was investigated in clinical and mouse models. H2S concentrations and survival was assessed in septic patients with lung infection. Animal experiments using a model of severe systemic multidrug-resistant P. aeruginosa infection were performed using mice with a constitutive knock-out of cystathionine-γ lyase (Cse) gene (Cse-/-) and wild-type mice with a physiological expression (Cse+/+). Experiments were repeated in mice after a) treatment with cyclophosphamide; b) bone marrow transplantation (BMT) from a Cse+/+ donor; c) treatment with H2S synthesis inhibitor aminooxyacetic acid (ΑΟΑΑ) or propargylglycine (PAG) and d) H2S donor sodium thiosulfate (STS) or GYY3147. Bacterial loads and myeloperoxidase activity were measured in tissue samples. The expression of quorum sensing genes (QS) was determined in vivo and in vitro. Cytokine concentration was measured in serum and incubated splenocytes. Patients survivors at day 28 had significantly higher serum H2S compared to non-survivors. A cut- off point of 5.3 μΜ discriminated survivors with sensitivity 92.3%. Mortality after 28 days was 30.9% and 93.7% in patients with H2S higher and less than 5.3 μΜ (p = 7 x 10−6). In mice expression of Cse and application of STS afforded protection against infection with multidrug-resistant P. aeruginosa. Cyclophosphamide pretreatment eliminated the survival benefit of Cse+/+ mice, whereas BMT increased the survival of Cse-/- mice. Cse-/- mice had increased pathogen loads compared to Cse+/+ mice. Phagocytic activity of leukocytes from Cse-/- mice was reduced but was restored after H2S supplementation. An H2S dependent down- regulation of quorum sensing genes of P.aeruginosa could be demonstrated in vivo and in vitro. Endogenous H2S is a potential independent parameter correlating with the outcome of P. aeruginosa. H2S provides resistance to infection by MDR bacterial pathogens.
Risk factors for in-hospital mortality in laboratory-confirmed COVID-19 patients in the Netherlands: A competing risk survival analysis

Background To date, survival data on risk factors for COVID-19 mortality in western Europe is limited, and none of the published survival studies have used a competing risk approach. This study aims to identify risk factors for in-hospital mortality in COVID-19 patients in the Netherlands, considering recovery as a competing risk. Methods In this observational multicenter cohort study we included adults with PCR-confirmed SARS-CoV-2 infection that were admitted to one of five hospitals in the Netherlands (March to May 2020). We performed a competing risk survival analysis, presenting cause-specific hazard ratios (HRCS) for the effect of preselected factors on the absolute risk of death and recovery. Results 1,006 patients were included (63.9% male; median age 69 years, IQR: 58–77). Patients were hospitalized for a median duration of 6 days (IQR: 3–13); 243 (24.6%) of them died, 689 (69.9%) recovered, and 74 (7.4%) were censored. Patients with higher age (HRCS 1.10, 95% CI 1.08–1.12), immunocompromised state (HRCS 1.46, 95% CI 1.08–1.98), who used anticoagulants or antiplatelet medication (HRCS 1.38, 95% CI 1.01–1.88), with higher modified early warning score (MEWS) (HRCS 1.09, 95% CI 1.01–1.18), and higher blood LDH at time of admission (HRCS 6.68, 95% CI 1.95–22.8) had increased risk of death, whereas fever (HRCS 0.70, 95% CI 0.52–0.95) decreased risk of death. We found no increased mortality risk in male patients, high BMI or diabetes. Conclusion Our competing risk survival analysis confirms specific risk factors for COVID-19 mortality in a the Netherlands, which can be used for prediction research, more intense in-hospital monitoring or prioritizing particular patients for new treatments or vaccination.
Age-related changes in crystalline lens tilt and decentration: swept-source OCT study

In this study, the crystalline lens tilt and decentration were measured using swept-source coherence tomography. The crystalline lens position correlated with ocular parameters and may change over time. Purpose: To investigate the age-related tilt and decentration of crystalline lenses using a swept-source optical coherence tomography biometer (SS-OCT) (CASIA2, Tomey Corp.). Setting: Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. Design: Cross-sectional study. Methods: The direction and magnitude of the crystalline lens were evaluated in 230 participants with ages ranging from 7 to 90 years using SS-OCT. The participants were divided into 4 age groups, and the differences among the groups were analyzed. Multiple linear regression was used to investigate the main factors influencing crystalline lens tilt and decentration. Results: The natural crystalline lens tilted toward the inferotemporal direction with a mean magnitude of 4.3 ± 1.5 degrees (range 0.7 to 8.95 degrees). The mean decentration toward the superotemporal direction was 0.17 ± 0.12 mm (range 0.03 to 1.15 mm). There was mirror symmetry between the right and left eyes. There were statistically significant differences in the crystalline lens tilt and decentration among the age groups. Multiple linear regression showed that changes in crystalline lens tilt depended on angle α (P < .01) and anterior chamber depth (ACD; P = .008), whereas crystalline lens decentration depended on angle κ (P = .003), age (P < .01), and angle α (P = .002). Conclusions: Although there was a statistically significant difference in crystalline lens tilt and decentration among age groups, the variation in the crystalline lens position was partially affected by age. The crystalline lens tilt was greater in eyes with wider angle α and shallower ACD, whereas crystalline lens decentration was greater in younger eyes with wider angles κ and α.
Anhydrides as antimycotic agents added to polyethylene films for food packaging

Incorporation of free acids or salts of antimycotic food additives, including propionic acid, benzoic acid or sorbic acid, into low-density polyethylene (LDPE) films failed to inhibit mould growth when the films contacted inoculated media. However, LDPE films into which benzoic anhydride was incorporated exhibited antimycotic activity when in contact with media and cheese. Benzoic anhydride, which had been added to LDPE film, was hydrolysed within 5h and detected as benzoic acid in potato dextrose agar (PDA) and cheese after contact with the film. LDPE films, into which 1% benzoic anhydride was incorporated, completely inhibited Rhizopus stolonifer. Penicillium spp. , and Aspergillus toxicarius growth on PDA. Lower amounts of anhydride partially inhibited growth by increasing the lag phase and reducing the rate of growth in most cases. LDPE films incorporated with 0.5–2% benzoic anhydride delayed mould growth on cheese. These data suggest that addition of antimycotic agents to LDPE during film manufacture may be a feasible way of controlling surface mould growth in foods such as cheese.
Processing of Honey: A Review

Thermal processing of honey eliminates the microorganisms responsible for spoilage. Microwave heating, infrared heating, ultrasound processing, and membrane processing have been explored as alternatives to conventional heat processing. Microwave heating provides a rapid method for achieving the desired level of yeast reduction with reduced thermal damage. Infrared heating is not as rapid as microwave heating but desired results are achieved in a relatively shorter duration (3 to 4 minutes) compared to the conventional method. Membrane processing is an athermal process and very effective in the complete removal of yeast cells from honey. Microfiltration and ultrafiltration could be employed to produce enzyme-enriched honey besides clarified honey.
Full-length ribosome density prediction by a multi-input and multi-output model

Translation elongation is regulated by a series of complicated mechanisms in both prokaryotes and eukaryotes. Although recent advance in ribosome profiling techniques has enabled one to capture the genome-wide ribosome footprints along transcripts at codon resolution, the regulatory codes of elongation dynamics are still not fully understood. Most of the existing computational approaches for modeling translation elongation from ribosome profiling data mainly focus on local contextual patterns, while ignoring the continuity of the elongation process and relations between ribosome densities of remote codons. Modeling the translation elongation process in full-length coding sequence (CDS) level has not been studied to the best of our knowledge. In this paper, we developed a deep learning based approach with a multi-input and multi-output framework, named RiboMIMO, for modeling the ribosome density distributions of full-length mRNA CDS regions. Through considering the underlying correlations in translation efficiency among neighboring and remote codons and extracting hidden features from the input full-length coding sequence, RiboMIMO can greatly outperform the state-of-the-art baseline approaches and accurately predict the ribosome density distributions along the whole mRNA CDS regions. In addition, RiboMIMO explores the contributions of individual input codons to the predictions of output ribosome densities, which thus can help reveal important biological factors influencing the translation elongation process. The analyses, based on our interpretable metric named codon impact score, not only identified several patterns consistent with the previously-published literatures, but also for the first time (to the best of our knowledge) revealed that the codons located at a long distance from the ribosomal A site may also have an association on the translation elongation rate. This finding of long-range impact on translation elongation velocity may shed new light on the regulatory mechanisms of protein synthesis. Overall, these results indicated that RiboMIMO can provide a useful tool for studying the regulation of translation elongation in the range of full-length CDS.
Interferon regulatory factor 6 correlates with the progression of non-small cell lung cancer and can be regulated by miR-320.

OBJECTIVES The expression of interferon regulatory factor 6 (IRF6) has been reported in several cancer types, but its roles underlying the progression of lung cancer have not been detailedly investigated. METHODS The pairs of lung cancer tissues and para-carcinoma tissues and The Cancer Genome Atlas database were collected to detect IRF6 expression. Cell counting kit-8, transwell and terminal-deoxynucleoitidyl transferase-mediated nick end labelling assays were used to evaluate cell proliferation, migration and apoptosis. KEY FINDINGS A significant up-regulation of IRF6 in both lung adenocarcinoma and lung squamous cell carcinoma tissues compared with normal non-tumor tissues. Subsequently, Immunostaining also revealed that canceration of lung tissues predisposed to evoke IRF6 expression. In vitro experiments revealed the antitumour effects, including growth and migration inhibition, of IRF6 siRNA transfection. Considering miR-320 as an endogenous inhibitor to IRF6, miR-320 mimics transfection led to the inhibition of proliferation and migration of lung cancer cells. However, overexpressed IRF6 neutralized the antineoplastic activities of miR-320 in lung cancer cells. CONCLUSIONS The miR-320/IRF6 signalling axis was implicated in pulmonary canceration. miR-320 as an endogenous inhibitor of IRF6 provided a novel therapeutic strategy for the treatment of lung cancer.
Echolocation click parameters and biosonar behaviour of the dwarf sperm whale (Kogia sima)

ABSTRACT Dwarf sperm whales (Kogia sima) are small toothed whales that produce narrow-band high-frequency (NBHF) echolocation clicks. Such NBHF clicks, subject to high levels of acoustic absorption, are usually produced by small, shallow-diving odontocetes, such as porpoises, in keeping with their short-range echolocation and fast click rates. Here, we sought to address the problem of how the little-studied and deep-diving Kogia can hunt with NBHF clicks in the deep sea. Specifically, we tested the hypotheses that Kogia produce NBHF clicks with longer inter-click intervals (ICIs), higher directionality and higher source levels (SLs) compared with other NBHF species. We did this by deploying an autonomous deep-water vertical hydrophone array in the Bahamas, where no other NBHF species are present, and by taking opportunistic recordings of a close-range Kogia sima in a South African harbour. Parameters from on-axis clicks (n=46) in the deep revealed very narrow-band clicks (root mean squared bandwidth, BWRMS, of 3±1 kHz), with SLs of up to 197 dB re. 1 µPa peak-to-peak (μPapp) at 1 m, and a half-power beamwidth of 8.8 deg. Their ICIs (mode of 245 ms) were much longer than those of porpoises (<100 ms), suggesting an inspection range that is longer than detection ranges of single prey, perhaps to facilitate auditory streaming of a complex echo scene. On-axis clicks in the shallow harbour (n=870) had ICIs and SLs in keeping with source parameters of other NBHF cetaceans. Thus, in the deep, dwarf sperm whales use a directional, but short-range echolocation system with moderate SLs, suggesting a reliable mesopelagic prey habitat. Highlighted Article: Dwarf sperm whales produce echolocation clicks with short-range characteristics that are counterintuitive for their use in deep-diving foraging contexts in the open ocean.
Selective versus non-selective alpha-blockade prior to adrenalectomy for pheochromocytoma - systematic review and meta-analysis.

OBJECTIVE Alpha-adrenergic blockade is currently the first choice of preoperative treatment in patients with functional pheochromocytoma and sympathetic paraganglioma. Nevertheless, there is no consensus whether selective or non-selective alpha-blockade is superior for preventing both perioperative hemodynamic instability and complications. DESIGN Our study aimed to compare selective and non-selective alpha-blockade through a systematic review with meta-analysis. METHODS MEDLINE, Embase, Web of Science and Cochrane Library were searched for eligible studies. Randomized and observational studies comparing selective and non-selective alpha-blockade in pheochromocytoma and sympathetic paraganglioma surgery in adults were included. Data on perioperative hemodynamic parameters and postoperative outcomes were extracted. RESULTS Eleven studies with 1,344 patients were enrolled. Patients receiving selective alpha-blockade had higher maximum intraoperative systolic blood pressure (WMD 12.14 mm Hg, 95% CI 6.06-18.21, p<0.0001) compared to those treated with non-selective alpha-blockade. Additionally, in the group pretreated with selective alpha-blockers, intraoperative vasodilators were used more frequently (OR 2.46, 95% CI 1.44-4.20, p=0.001). Patients treated with selective alpha-blockers had lower minimum intraoperative systolic blood pressure (WMD -2.03 mmHg, 95% CI -4.06 to -0.01, p=0.05) and shorter length of hospital stay (WMD -0.58 days, 95% CI -1.12 to -0.04, p=0.04). Operative time, overall morbidity and mortality did not differ between the groups. CONCLUSIONS This meta-analysis shows non-selective alpha-blockade was more effective in preventing intraoperative blood pressure fluctuations while maintaining comparable risk of both intraoperative and postoperative hypotension and overall morbidity.
MEMBRANE BENDING IS CRITICAL FOR ASSESSING THE THERMODYNAMIC STABILITY OF PROTEINS IN THE MEMBRANE

The ability of biological membranes to bend is critical to understanding the interaction between proteins and the lipid bilayer. Experimental and computational studies have shown that the membrane can bend to expose charged and polar residues to the lipid headgroups and water, greatly reducing the cost of protein insertion. However, current computational approaches are poorly equipped to accurately model such deformation; atomistic simulations often do not reach the time-scale necessary to observe large-scale rearrangement, and continuum approaches assume a flat, rigid bilayer. In this thesis we present an efficient computational model of a deformable membrane for probing these interactions with elasticity theory and continuum electrostatics. To validate the model, we first investigate the insertion of three membrane proteins and three aqueous proteins. The model finds the membrane proteins and aqueous proteins stable and unstable in the membrane, respectively. We also investigate the sensitivity of these predictions to changes in several key parameters. The model is then applied to interactions between the membrane and the voltage sensor segments of voltage-gated potassium channels. Despite their high numbers of basic residues, experiments have shown that voltage sensors can be stably accommodated in the membrane. For simple continuum electrostatics approaches that assume a flat membrane, the penalty of inserting these charged residues would seem to prohibit voltage sensor insertion. However, in our method the membrane deforms to enable interaction between solvent and the charged residues. Our calculations predict that the highly charged S4 helices of several potassium channels are in fact stable in the membrane, in accord with experimental observations. Experimental and computational evidence has shown that the cost for inserting multiple charged amino acids into the membrane is not additive; it is not as costly to insert a second charge once a first has already been inserted. Our model reflects this phenomenon and provides a simple mechanical explanation linked to membrane deformation. We additionally consider the energetics of passive ion penetration into the membrane from bulk solvent. We use coarse-grained molecular dynamics to guide our input parameters and show that ion permeation energy profiles agree with atomistic simulations when membrane bending is included.
Performance in male and female elite tennis across season of birth

ABSTRACT In the field of sports, there is an overrepresentation of athletes born in the initial months of the selection year, and an underrepresentation of athletes born in the latter months of the selection year. This season of birth effect appears to lead to a disadvantage in performance, even though with a considerable variability regarding age, sex, and skill. This study addressed season of birth effects on performance with the best one hundred male and female tennis players in the world. Specifically, we examined whether season of birth moderates the association of body height and ranking position with tennis performance. The main findings indicated that body height and rank associated in the expected direction with first service wins, break points saved, and a success rate describing the ratio of match wins to match defeats. For females born later in the selection year, however, height was unrelated to the percentage of first service wins or break points saved, and occupying higher positions in the ranking did not contribute to improve the ratio of wins to defeats. These findings suggest that season of birth effects on performance might operate for women but not for men when comparing highly selected populations such as the best tennis players in the world.
Sequential Instance Refinement for Cross-Domain Object Detection in Images

Cross-domain object detection in images has attracted increasing attention in the past few years, which aims at adapting the detection model learned from existing labeled images (source domain) to newly collected unlabeled ones (target domain). Existing methods usually deal with the cross-domain object detection problem through direct feature alignment between the source and target domains at the image level, the instance level (i.e., region proposals) or both. However, we have observed that directly aligning features of all object instances from the two domains often results in the problem of negative transfer, due to the existence of (1) outlier target instances that contain confusing objects not belonging to any category of the source domain and thus are hard to be captured by detectors and (2) low-relevance source instances that are considerably statistically different from target instances although their contained objects are from the same category. With this in mind, we propose a reinforcement learning based method, coined as sequential instance refinement, where two agents are learned to progressively refine both source and target instances by taking sequential actions to remove both outlier target instances and low-relevance source instances step by step. Extensive experiments on several benchmark datasets demonstrate the superior performance of our method over existing state-of-the-art baselines for cross-domain object detection.