Miracle-dz/UniFAR-FTUs huggingface dataset:
Thirdhand smoke exposure causes replication stress and impaired transcription in human lung cells

Thirdhand cigarette smoke (THS) is a newly described toxin that lingers in the indoor environment long after cigarettes have been extinguished. Emerging results from both cellular and animal model studies suggest that THS is a potential human health hazard. DNA damage derived from THS exposure could have genotoxic consequences that would lead to the development of diseases. However, THS exposure‐induced interference with fundamental DNA transactions such as replication and transcription, and the role of DNA repair in ameliorating such effects, remain unexplored. Here, we found that THS exposure increased the percentage of cells in S‐phase, suggesting impaired S‐phase progression. Key DNA damage response proteins including RPA, ATR, ATM, CHK1, and BRCA1 were activated in lung cells exposed to THS, consistent with replication stress. In addition, THS exposure caused increased 53BP1 foci, indicating DNA double‐strand break induction. Consistent with these results, we observed increased micronuclei formation, a marker of genomic instability, in THS‐exposed cells. Exposure to THS also caused a significant increase in phosphorylated RNA Polymerase II engaged in transcription elongation, suggesting an increase in transcription‐blocking lesions. In agreement with this conclusion, ongoing RNA synthesis was very significantly reduced by THS exposure. Loss of nucleotide excision repair exacerbated the reduction in RNA synthesis, suggesting that bulky DNA adducts formed by THS are blocks to transcription. The adverse impact on both replication and transcription supports genotoxic stress as a result of THS exposure, with important implications for both cancer and other diseases.
Evaluating the co-use of opioids and cannabis for pain among current users using hypothetical purchase tasks

Background: Cannabinoids may potentiate opioid analgesia and therefore could be used to reduce reliance on opioids for analgesia. Aims: The current study evaluated whether the concurrent availability of cannabis influences opioid consumption using a behavioral economic demand framework. Methods: An online survey assessed cannabis and opioid use frequency and dependence measures, pain severity, and demand for both cannabis and opioids alone and when concurrently available using hypothetical purchase tasks. Adults reporting current use of opioids for pain management and past 30-day cannabis exposure (N=155) completed two hypothetical purchase tasks in which only grams of cannabis or units of participants’ index opioids were available for purchase, and two hypothetical tasks in which both were concurrently available and the price of one drug increased whereas the other was kept constant. Paired-sample t-tests compared the demand of each drug alone with when it was available concurrently with an alternative. Results: Demand intensity was significantly reduced and demand elasticity was significantly increased for both cannabis and opioids when the alternate commodity was available, although the reductions in cannabis consumption were more pronounced than they were for opioid consumption in the presence of the alternate commodity. Conclusions: These data provide behavioral economic evidence that cannabis access may modestly reduce demand for opioids in persons who have pain. Additional clinical studies that evaluate the analgesic effects of cannabis and cannabis-opioid effects on pain are warranted.
Human Peripheral Blood-Derived Endothelial Colony-Forming Cells Are Highly Similar to Mature Vascular Endothelial Cells yet Demonstrate a Transitional Transcriptomic Signature

Endothelial colony-forming cells (ECFC) are currently considered as a promising cell population for the pre-endothelialization or pre-vascularization of tissue-engineered constructs, including small-diameter biodegradable vascular grafts. However, the extent of heterogeneity between ECFC and mature vascular endothelial cells (EC) is unclear. Here, we performed a transcriptome-wide study to compare gene expression profiles of ECFC, human coronary artery endothelial cells (HCAEC), and human umbilical vein endothelial cells (HUVEC). Characterization of the abovementioned cell populations was carried out by immunophenotyping, tube formation assay, and evaluation of proliferation capability while global gene expression profiling was conducted by means of RNA-seq. ECFC were similar to HUVEC in terms of immunophenotype (CD31+vWF+KDR+CD146+CD34-CD133-CD45-CD90-) and tube formation activity yet had expectedly higher proliferative potential. HCAEC and HUVEC were generally similar to ECFC with regards to their global gene expression profile; nevertheless, ECFC overexpressed specific markers of all endothelial lineages (NRP2, NOTCH4, LYVE1), in particular lymphatic EC (LYVE1), and had upregulated extracellular matrix and basement membrane genes (COL1A1, COL1A2, COL4A1, COL4A2). Proteomic profiling for endothelial lineage markers and angiogenic molecules generally confirmed RNA-seq results, indicating ECFC as an intermediate population between HCAEC and HUVEC. Therefore, gene expression profile and behavior of ECFC suggest their potential to be applied for a pre-endothelialization of bioartificial vascular grafts, whereas in terms of endothelial hierarchy they differ from HCAEC and HUVEC, having a transitional phenotype.
Application of prenatal ultrasonography and magnetic resonance imaging on fetal agenesis of corpus callosum.

OBJECTIVES To evaluate the diagnostic value and clinical application of prenatal ultrasonography (US) and Magnetic Resonance Imaging (MRI) for different types of fetal Agenesis of the Corpus Callosum (ACC). MATERIAL AND METHODS There were 42 cases of fetal ACC discovered by routine US, including complete ACC 18 cases and partial ACC 24 cases, checked by MRI within 1 week. The results were confirmed by head ultrasound after birth or brain biopsy after labor induction. RESULTS From prenatal ultrasonic diagnosis, 18 cases were complete ACC and 24 cases were partial ACC. MRI was able to find complete ACC in 11 cases, partial ACC in 16 cases, and non-ACC in 15 cases. Labor induction or birth confirmed that, 11 cases were complete ACC, 14 cases were partial ACC, and 17 cases were non-ACC.The results of different types of ACC were detected by ultrasound and MRI were statistically significant (p < 0.05). MRI examination was superior to ultrasound in specificity, positive predictive value, negative predictive value, Youden index, and diagnostic index. CONCLUSIONS MRI is high specific degrees, diagnostic performance is satisfactory, should be use as a necessary method for prenatal definitive diagnosis of ACC. However, prenatal ultrasound can be tested repeatedly and can be combined with blood flow imaging detection in real time, and it is still the preferred method for screening fetal structural malformation in a comprehensive way, which is suitable for general screening of ACC.
Learning transferable deep convolutional neural networks for the classification of bacterial virulence factors

MOTIVATION Identification of virulence factors (VFs) is critical to the elucidation of bacterial pathogenesis and prevention of related infectious diseases. Current computational methods for VF prediction focus on binary classification or involve only several class(es) of VFs with sufficient samples. However, thousands of VF classes are present in real-world scenarios, and many of them only have a very limited number of samples available. RESULTS We first construct a large VF dataset, covering 3,446 VF classes with 160,495 sequences, and then propose deep convolutional neural network (CNN) models for VF classification. We show that (i) for common VF classes with sufficient samples, our models can achieve state-of-the-art performance with an overall accuracy of 0.9831 and an F1-score of 0.9803; (ii) for uncommon VF classes with limited samples, our models can learn transferable features from auxiliary data and achieve good performance with accuracy ranging from 0.9277 to 0.9512 and F1-score ranging from 0.9168 to 0.9446 when combined with different predefined features, outperforming traditional classifiers by 1%-13% in accuracy and by 1%-16% in F1-score. AVAILABILITY All of our datasets are made publicly available at http://www.mgc. ac.cn/VFNet/, and the source code of our models is publicly available at https://github.com/zhengdd0422/VFNet. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
High-flow Nasal Oxygen Versus Standard Oxygen During Flexible Bronchoscopy in Lung Transplant Patients

Background: Diagnostic and interventional flexible bronchoscopy (FB) is increasingly utilized in complex and high-risk patients. Patients are often sedated for comfort and procedure facilitation and hypoxia is commonly observed in this setting. We hypothesized that high-flow nasal oxygen (HFNO) would reduce the incidence of patients experiencing oxygen desaturation. Methods: In this randomized controlled trial, postlung transplant patients booked for FB with transbronchial lung biopsy were assigned to either HFNO or low-flow nasal oxygen (LFNO). The patient and bronchoscopist were blinded to group allocation. The primary endpoint was the proportion of patients experiencing mild desaturation [peripheral oxygen saturation (SpO2)<94%]. Secondary endpoints included desaturation (SpO2<90%), the number of airway interventions required and procedure interruptions, the duration of oxygen desaturation and patient, bronchoscopist and anesthesiologist satisfaction scores. Results: The trial analyzed data from 76 patients (LFNO, n=39; HFNO, n=37). HFNO reduced the proportion of patients experiencing SpO2<94% (43.2% vs. 89.7%, P<0.001) and SpO2<90% (16.2% vs. 69.2%, P<0.001). The FB was interrupted 11 times in 9 patients in the LFNO group, whereas there were no interruptions in the HFNO group. There were no differences in patient and bronchoscopist satisfaction scores between groups, anesthesiologists had higher satisfaction scores when using HFNO (P<0.001). Conclusion: Hypoxia occurred less commonly in postlung transplant patients receiving HFNO during FB. Further studies are warranted in other high-risk populations undergoing longer duration FB.
A dynamic model of UVR8 photoreceptor signaling in UV-B-acclimated Arabidopsis.

The photoreceptor UVR8 mediates numerous photomorphogenic responses of plants to UV-B wavelengths by regulating transcription. Studies with purified UVR8 and seedlings not previously exposed to UV-B have generated a model for UVR8 action in which dimeric UVR8 rapidly monomerises in response to UV-B exposure to initiate signaling. However, the mechanism of UVR8 action in UV-B-acclimated plants growing under photoperiodic conditions, where UVR8 exists in a dimer/monomer photo-equilibrium, is poorly understood. We examined UVR8 dimer/monomer status, gene expression responses, amounts of key UVR8 signaling proteins and their interactions with UVR8 in UV-B-acclimated Arabidopsis. We show that in UV-B-acclimated plants UVR8 can mediate a response to a 15-fold increase in UV-B without any increase in abundance of UVR8 monomer. Following transfer to elevated UV-B, monomers show increased interaction with both COP1, to initiate signaling, and RUP2, to maintain the photo-equilibrium when the dimer/monomer cycling rate increases. Native RUP1 is present in low abundance compared with RUP2. We present a model for UVR8 action in UV-B-acclimated plants growing in photoperiodic conditions that incorporates dimer and monomer photoreception, dimer/monomer cycling, abundance of native COP1 and RUP proteins, and interactions of the monomer population with COP1, RUP2 and potentially other proteins.
Fabrication and characterization of a novel compliant small-diameter PET/PU/PCL triad-hybrid vascular graft

Nanomaterial structures are highly contributive in tissue engineering vascular scaffolds (TEVS) due to their ability to mimic the nanoscale dimension of the natural extracellular matrix (ECM) and the existing mechanical match between the native blood vessel and the scaffold as a vascular graft. The aim of this study was to develop and mechanically improve the nanofibrous triad-hybrid scaffolds with different composite ratios of polyethylene terephthalate (PET), polyurethane (PU), and polycaprolactone (PCL). The morphological, biological, mechanical, and biomechanical properties of the neat and hybrid structures were examined using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), tensile strength, compliance, burst pressure, MTT assay, and by implanting the specimens under rat skin to explore the immune system in vivo. The results showed that the fiber diameter and porosity changes in the triad-hybrid electrospun scaffold ranged within 388 ± 88 to 547 ± 89 nm and 56.60 ± 2.06% to 75.00 ± 1.94%, respectively. In addition, the changes in the tensile strength and force in the scaffolds were within the ranges 2.7 ± 0.44 to 5.27 ± 0.83 MPa and 2.68 ± 0.19 to 10.03 ± 0.75 MPa, respectively. Also, the compliance and burst pressure of the structures were reported as 4.05 ± 0.21 to 7.09 ± 0.49 and 1623 ± 329 to 2560 ± 121 mmHg, respectively. According to the MTT assay, high cell viability was observed on the triad-hybrid structures with a high percentage of PET when compared to that of PU. The findings of this research demonstrate that the PET/PU/PCL triad-hybrid vascular scaffold has enough potential to be used in vascular tissue engineering application.
Renal Function Improvement Following ANG-3777 Treatment in Patients at High Risk for Delayed Graft Function After Kidney Transplantation

Supplemental Digital Content is available in the text. Background. Patients (20%–50%) undergoing renal transplantation experience acute kidney injury resulting in delayed graft function. ANG-3777 is an hepatocyte growth factor mimetic that binds to the c-MET receptor. In animal models, ANG-3777 decreases apoptosis, increases proliferation, and promotes organ repair and function. Methods. This was a randomized, double-blind, placebo-controlled, phase 2 trial of patients undergoing renal transplantation with <50 cc/h urine output for 8 consecutive hours over the first 24 hours posttransplantation, or creatinine reduction ratio <30% from pretransplantation to 24 hours posttransplantation. Subjects were randomized as 2:1 to 3, once-daily IV infusions of ANG-3777, 2 mg/kg (n = 19), or placebo (n = 9). Primary endpoint: time in days to achieve ≥1200 cc urine for 24 hours. Results. Patients treated with ANG-3777 were more likely to achieve the primary endpoint of 1200 cc urine for 24 hours by 28 days posttransplantation (83.3% versus 50% placebo; log-rank test: χ2 = 2.799, P = 0.09). Compared with placebo, patients in the ANG-3777 arm had larger increases in urine output; lower serum creatinine; greater reduction in C-reactive protein and neutrophil gelatinase-associated lipocalin; fewer dialysis sessions and shorter duration of dialysis; fewer hospital days; significantly less graft failure; and higher estimated glomerular filtration rate. Adverse events occurred in a similar percentage of subjects in both arms. Events per subject were twice as high in the placebo arm. Conclusions. There was an efficacy signal for improved renal function in subjects treated with ANG-3777 relative to placebo, with a good safety profile.
Diatoms Biomass as a Joint Source of Biosilica and Carbon for Lithium-Ion Battery Anodes

The biomass of one type cultivated diatoms (Pseudostaurosira trainorii), being a source of 3D-stuctured biosilica and organic matter—the source of carbon, was thermally processed to become an electroactive material in a potential range adequate to become an anode in lithium ion batteries. Carbonized material was characterized by means of selected solid-state physics techniques (XRD, Raman, TGA). It was shown that the pyrolysis temperature (600 °C, 800 °C, 1000 °C) affected structural and electrochemical properties of the electrode material. Biomass carbonized at 600 °C exhibited the best electrochemical properties reaching a specific discharge capacity of 460 mAh g−1 for the 70th cycle. Such a value indicates the possibility of usage of biosilica as an electrode material in energy storage applications.
Subthalamic Nucleus Stimulation in Pediatric Isolated Dystonia: A 10-Year Follow-up

ABSTRACT: Objective: To evaluate the short-term and long-term clinical effectiveness and safety of subthalamic nucleus deep brain stimulation (STN-DBS) for medically intractable pediatric isolated dystonia. Methods: Using a longitudinal retrospective design, we assessed the clinical outcomes of nine patients who underwent STN-DBS for treatment-refractory pediatric isolated dystonia one decade ago (mean age at surgery: 15.9 ± 4.5 years). The primary clinical outcome used was assessed by retrospective video analyses of patients’ dystonia symptoms using the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS). Clinical assessments were performed at baseline, 1-year follow-up (1-yr FU), and 10-year follow-up (10-yr FU). Adverse side effects, including surgery-related, device-related, and stimulation-related effects, were also documented. Results: After STN-DBS surgery, the mean improvement in the BFMDRS motor score was 77.1 ± 26.6% at 1-yr FU and 90.4 ± 10.4% at 10-yr FU. Similarly, the mean BFMDRS disability score was improved by 69.5 ± 13.6% at 1-yr FU and by 86.5 ± 13.9% at 10-yr FU. The clinical improvements gained at 10-yr FU were significantly larger than those observed at 1-yr FU. Negative correlations were found between the duration of disease to age at surgery ratio (DD/AS) and the improvements in the BFMDRS motor score and total score at 1-yr FU and 10-yr FU. Conclusion: To our knowledge, this study provides the first clinical evidence for the short- and long-term effectiveness and safety of STN-DBS for pediatric isolated dystonia. Additionally, putative evidence is provided that earlier STN-DBS intervention in patients with refractory pediatric isolated dystonia may improve short- and long-term clinical outcomes.
Nicotinamide mononucleotide adenylyltransferase uses its NAD+ substrate-binding site to chaperone phosphorylated Tau

Tau hyper-phosphorylation and deposition into neurofibrillary tangles have been found in brains of patients with Alzheimer’s disease (AD) and other tauopathies. Molecular chaperones are involved in regulating the pathological aggregation of phosphorylated Tau (pTau) and modulating disease progression. Here, we report that nicotinamide mononucleotide adenylyltransferase (NMNAT), a well-known NAD+ synthase, serves as a chaperone of pTau to prevent its amyloid aggregation in vitro as well as mitigate its pathology in a fly tauopathy model. By combining NMR spectroscopy, crystallography, single-molecule and computational approaches, we revealed that NMNAT adopts its enzymatic pocket to specifically bind the phosphorylated sites of pTau, which can be competitively disrupted by the enzymatic substrates of NMNAT. Moreover, we found that NMNAT serves as a co-chaperone of Hsp90 for the specific recognition of pTau over Tau. Our work uncovers a dedicated chaperone of pTau and suggests NMNAT as a key node between NAD+ metabolism and Tau homeostasis in aging and neurodegeneration.
Impact of Radiographic Bronchiectasis in COPD

BACKGROUND: COPD and bronchiectasis frequently coexist, which creates an emerging phenotype with a worse prognosis. However, the impact of bronchiectasis on the natural history of COPD has not been fully evaluated and is still controversial. This meta-analysis was performed to clarify the associations of the presence of bronchiectasis with the prognosis and quality of life of patients with COPD. METHODS: A systematic review and meta-analysis was performed following a search of medical databases, and included articles published up to April 2019. The following outcome measures were analyzed: age, sex, smoking history, body mass index, exacerbation rate, lung function, inflammatory biomarkers, albumin, colonization by potentially pathogenic microorganisms, Pseudomonas aeruginosa isolates, Haemophilus influenzae isolates, hospital admissions, and mortality. RESULTS: A total of 415,257 subjects with COPD from 18 observational studies were eligible; bronchiectasis was present in 25,929 subjects (6.24%). The coexistence of COPD and bronchiectasis occurred more often in older subjects with lower body mass index. The presence of bronchiectasis in the subjects with COPD increased the risk of daily sputum production (odds ratio [OR] 1.80, 95% CI 1.24–2.61), exacerbation (weighted mean difference [WMD] 0.72 times, 95% CI 0.59–0.85), frequent hospital admissions (WMD 0.35 times, 95% CI 0.21–0.49), and follow-up (>3 years) mortality (OR 2.26, 95% CI 0.95–5.36). The subjects with COPD and bronchiectasis showed poorer pulmonary function (FEV1/FVC: WMD –3.37%, 95% CI –5.63 to –1.11), lower albumin (Standardized mean difference [SMD] –0.17, 95% CI –0.26 to –0.08), elevated C-reactive protein (SMD 0.40, 95% CI 0.06–0.74), a greater proportion of chronic colonization by potentially pathogenic microorganisms (OR 6.65, 95% CI 4.44–9.95), and a higher isolation rate of P. aeruginosa (OR 5.13, 95% CI 4.89–5.38) or H. influenzae (OR 1.90, 95% CI 1.29–2.79) than the subjects with COPD without bronchiectasis. CONCLUSIONS: This meta-analysis confirmed the significant associations of the presence of bronchiectasis with the natural history, disease course, and outcomes in COPD. The COPD-bronchiectasis phenotype had adverse effects on subjects’ health condition and prognosis.
Golgi Outposts Locally Regulate Microtubule Orientation in Neurons but Are Not Required for the Overall Polarity of the Dendritic Cytoskeleton

Golgi are emerging as key regulators of acentrosomal microtubule networks. In neurons, the role of dendrite-specific Golgi outposts in creating or maintaining the unique organization of the dendritic cytoskeleton is an open question. Microtubule-organizing centers often play a central role in organizing the cellular microtubule networks that underlie cell function. In neurons, microtubules in axons and dendrites have distinct polarities. Dendrite-specific Golgi “outposts,” in particular multicompartment outposts, have emerged as regulators of acentrosomal microtubule growth, raising the question of whether outposts contribute to establishing or maintaining the overall polarity of the dendritic microtubule cytoskeleton. Using a combination of genetic approaches and live imaging in a Drosophila model, we found that dendritic microtubule polarity is unaffected by eliminating known regulators of Golgi-dependent microtubule organization including the cis-Golgi matrix protein GM130, the fly AKAP450 ortholog pericentrin-like protein, and centrosomin. This indicates that Golgi outposts are not essential for the formation or maintenance of a dendrite-specific cytoskeleton. However, the overexpression of GM130, which promotes the formation of ectopic multicompartment units, is sufficient to alter dendritic microtubule polarity. Axonal microtubule polarity is similarly disrupted by the presence of ectopic multicompartment Golgi outposts. Notably, multicompartment outposts alter microtubule polarity independently of microtubule nucleation mediated by the γ-tubulin ring complex. Thus, although Golgi outposts are not essential to dendritic microtubule polarity, altering their organization correlates with changes to microtubule polarity. Based on these data, we propose that the organization of Golgi outposts is carefully regulated to ensure proper dendritic microtubule polarity.