Miracle-dz/UniFAR-FTUs huggingface dataset:
TREX1 degrades the 3′ end of the small DNA oligonucleotide products of nucleotide excision repair in human cells

Abstract The nucleotide excision repair (NER) machinery removes UV photoproducts from DNA in the form of small, excised damage-containing DNA oligonucleotides (sedDNAs) ∼30 nt in length. How cells process and degrade these byproducts of DNA repair is not known. Using a small scale RNA interference screen in UV-irradiated human cells, we identified TREX1 as a major regulator of sedDNA abundance. Knockdown of TREX1 increased the level of sedDNAs containing the two major UV photoproducts and their association with the NER proteins TFIIH and RPA. Overexpression of wild-type but not nuclease-inactive TREX1 significantly diminished sedDNA levels, and studies with purified recombinant TREX1 showed that the enzyme efficiently degrades DNA located 3′ of the UV photoproduct in the sedDNA. Knockdown or overexpression of TREX1 did not impact the overall rate of UV photoproduct removal from genomic DNA or cell survival, which indicates that TREX1 function in sedDNA degradation does not impact NER efficiency. Taken together, these results indicate a previously unknown role for TREX1 in promoting the degradation of the sedDNA products of the repair reaction. Because TREX1 mutations and inefficient DNA degradation impact inflammatory and immune signaling pathways, the regulation of sedDNA degradation by TREX1 may contribute to photosensitive skin disorders.
Inhibition effect of epigallocatechin gallate on the growth and biofilm formation of Vibrio parahaemolyticus

Vibrio parahaemolyticus is a common marine foodborne pathogen that causes gastroenteritis. With the long‐term use of antibiotics, many bacteria become resistant; therefore, developing antibiotic‐free antimicrobial strategies is urgent. Epigallocatechin gallate (EGCG), a constituent of polyphenols present abundantly in tea extract, has broad‐spectrum antibacterial activity and is non‐toxic. Here, we take advantage of these properties of EGCG to evaluate its inhibition effect on the growth and biofilm formation of V. parahaemolyticus 17802, and explore its antibacterial mechanism. It was found that EGCG showed antibacterial activity against V. parahaemolyticus 17802, and the minimum inhibitory concentration (MIC) was estimated to be 128 μg ml−1. Results of crystal violet staining and confocal laser scanning microscope (CLSM) evidenced that EGCG hindered its biofilm formation. Moreover, the swimming motility and extracellular polysaccharides were also notably inhibited. The antibacterial mechanism was further confirmed by several assays, such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), and live/dead staining assay, together with membrane permeability assay, which all suggested that EGCG caused damage to cell membrane and made it lose integrity, eventually resulting in the death of V. parahaemolyticus 17802. The bactericidal activity of EGCG verified its potential as a promising candidate to combat foodborne pathogen.
Bacillus subtilis BR4 derived stigmatellin Y interferes Pqs‐PqsR mediated quorum sensing system of Pseudomonas aeruginosa

Cell‐to‐cell communication is essentially required in bacteria for the production of multiple virulence factors and successful colonization in the host. Targeting the virulence factors production without hampering the growth of the pathogens is a potential strategy to control pathogenesis. To accomplish this, a total of 43 mangrove isolates were screened for quorum quenching (QQ) activity against Pseudomonas aeruginosa (PA), in which eight bacteria have shown antibiofilm activity without hampering the growth of the PA. Prominent QQ activity was observed in Bacillus subtilis BR4. Previously, we found that BR4 produces stigmatellin Y, a structural analogue of PQS signal of PA, which could competitively bind with PqsR receptor and inhibits the quorum sensing (QS) system of PA. Further, stigmatellin Y containing ethyl acetate extract (S‐EAE) (100 µg ml−1) of BR4 significantly inhibits (p < 0.001) the biofilm formation of PA. Confocal laser scanning microscope (CLSM) and scanning electron microscope (SEM) analysis also fortified the QQ activity of BR4. Furthermore, S‐EAE of BR4 (500 µg ml−1) has significantly reduced the production of virulence factors, including protease, elastase, pyocyanin and extracellular polysaccharides substances. Furthermore, liquid chromatography–mass spectrometry (LC–MS)/MS analysis affirms that BR4 intercepts the PQS‐mediated QS system by reducing the synthesis of as many PQS signals, including precursor molecule (243.162313 Da) of PQS signal. Thus, S‐EAE of B. subtilis BR4 could be used as a promising therapeutic agent to combat QS system‐mediated pathogenesis of PA. Further therapeutic potentials of stigmatellin Y to be evaluated in clinical studies for the treatment of multidrug resistant PA.
Pharmacological and molecular characterization of the A‐type muscarinic acetylcholine receptor from Anopheles gambiae

Muscarinic acetylcholine receptors (mAChRs) which are G protein‐coupled receptors play key roles in insect physiology. Whereas vertebrate mAChRs are important targets for pharmaceutical drugs, insect mAChRs are under‐exploited by the agro‐chemical industry. Moreover, insect mAChRs have been less well studied than their vertebrate counterparts. Their critical functions mean that a better knowledge of the insect mAChRs is crucial for the effort to develop a new molecular‐level strategy for insect pest management. Almost all insects possess three mAChRs named A, B and C which differ according to their coupling effector systems and their pharmacological profile. The aim of this study was to characterize the A‐type mAChR (mAChR‐A) from Anopheles gambiae which is the major vector of malaria in order to develop new strategies in pest management. In this paper, we reported that mAChR‐A is more expressed in adult mosquitoes than in larvae. Furthermore, using calcium imaging recordings, we found that the An. gambiae mAChR‐A expressed in Sf9 cells is activated by specific muscarinic agonists acetylcholine, muscarine and oxotremorine M and blocked by several mAChR antagonists. Moreover, using inhibitors of phosphoinositide pathway such as Gαq/11 protein blocker, we have shown that an increased intracellular calcium concentration elicited by the acetylcholine application was mediated by PLC/IP3R pathway. As a rise in intracellular calcium concentration could lead to an increase in the insecticide target sensitivity, these results suggest that An. gambiae mAChR‐A should not be only considered as a potential target for new molecules but also as a key element to optimize the efficacy of insecticide in vector control.
Task and information conflicts in the numerical Stroop task

Abstract Studies of the Stroop color‐word task have provided evidence for the existence of two conflicts: (1) an early task conflict between noting the relevant color and reading afforded by the irrelevant word (or word‐like stimuli), and (2) a late information conflict between the information provided by the word and the information provided by the color. Measurements of pupil changes, in addition to reaction time (RT), have extended understanding regarding these two conflicts. The current work examines the generalizability of such understanding. We ask whether similar processes work in the comparative judgment of numbers (e.g., in the numerical Stroop task). We present two experiments that support and extend the knowledge gained in the word‐color context to numerical processing. Similar to results with the Stroop color‐word task, we found a dissociation between RT and pupillometry and an early task conflict followed by an information conflict.
Effect of fungal indoor air pollutant 1-octen-3-ol on levels of reactive oxygen species and nitric oxide as well as dehydrogenases activities in drosophila melanogaster males

ABSTRACT Fungal pollution of indoor environments contributes to several allergic symptoms and represents a public health problem. It is well-established that 1-octen-3-ol, also known as mushroom alcohol, is a fungal volatile organic compound (VOC) commonly found in damp indoor spaces and responsible for the typical musty odor. Previously it was reported that exposure to 1-octen-3-ol induced inflammations and disrupted mitochondrial morphology and bioenergetic rate in Drosophila melanogaster. The aim of this study was to examine the influence of 1-octen-3-ol on dehydrogenase activity, apoptotic biomarkers, levels of nitric oxide (NO) and reactive oxygen species (ROS), as well as antioxidant enzymes activities. D. melanogaster flies were exposed to an atmosphere containing 1-octen-3-ol (2.5 or ∞l/L) for 24 hr. Data demonstrated that 1-octen-3-ol decreased dehydrogenases activity and NO levels but increased ROS levels accompanied by stimulation of glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities without altering caspase 3/7 activation. These findings indicate that adverse mitochondrial activity effects following exposure of D. melanogaster to 1-octen-3-ol, a fungal VOC, may be attributed to oxidant stress. The underlying mechanisms involved in adverse consequences of indoor fungal exposure appear to be related to necrotic but not apoptotic mechanisms. The adverse consequences were sex-dependent with males displaying higher sensitivity to 1-octen-3-ol. Based upon on the fact that the fly genome shares nearly 75% of disease-related genes to human exposure to this fungus may explain the adverse human responses to mold especially for males.
Mitigating and managing risks in mobile telecom projects

Proper risk management is one of the key drivers of successful project delivery. This is more apparent in competitive and fast growing industries such as telecommunication. To better understand the risks faced in construction and deployment of mobile telecom sites (MTS), a research was initiated to: (a) examine risks associated with deploying MTS, and (b) understand the means to mitigate and handle them. The first point was addressed in an earlier publication whilst this paper focuses on the second. Knowledge pertinent to mitigating and handling MTS risks has been acquired via rounds of interviews and questionnaire surveys with a panel of telecom industry experts. Flow charting has been utilized to code the acquired procedural knowledge and provide basis for developing a knowledge base expert system (KBES). The rules technique was selected for knowledge representation. Automation of the KBES is also demonstrated.
Inorganic Ferrocene Analogue [Fe(P4)2]2.

Inorganic metallocene derivatives containing only cyclo-Pn ligands have been targeted for more than 20 years, but their syntheses have never been achieved by pursuing the conventional route of using P4 phosphorus except for the generation of [Ti(η5-P5)2]2-. Herein, we report a facile one-step method for the synthesis of the homoleptic iron complex [Fe(P4)2]2- by the Zintl-phase-type precursor KP. 31P NMR analyses indicate that upon dissolving the KP phase in ethylenediamine P42- was generated only in the presence of 2,2,2-crypt. The amounts of cation-sequestering agents, the type of iron precursor, and their consuming ratio have a decisive impact on the yield of [Fe(P4)2]2-. Both the FeII and the FeIII precursors can oxidize P42- to give a concomitant product [(P7)Fe(P4)]3-, which can be partially inhibited by the addition of potassium to produce relatively pure crystalline [K(2,2,2-crypt)]2[Fe(P4)2].
Relationship between asthma and severe COVID-19: a national cohort study

Background We aimed to determine whether children and adults with poorly controlled or more severe asthma have greater risk of hospitalisation and/or death from COVID-19. Methods We used individual-level data from the Office for National Statistics Public Health Data Asset, based on the 2011 census in England, and the General Practice Extraction Service data for pandemic planning and research linked to death registration records and Hospital Episode Statistics admission data. Adults were followed from 1 January 2020 to 30 September 2021 for hospitalisation or death from COVID-19. For children, only hospitalisation was included. Results Our cohort comprised 35 202 533 adults and 2 996 503 children aged 12–17 years. After controlling for sociodemographic factors, pre-existing health conditions and vaccine status, the risk of death involving COVID-19 for adults with asthma prescribed low dose inhaled corticosteroids (ICS) was not significantly different from those without asthma. Adults with asthma prescribed medium and high dosage ICS had an elevated risk of COVID-19 death; HRs 1.18 (95% CI 1.14 to 1.23) and 1.36 (95% CI 1.28 to 1.44), respectively. A similar pattern was observed for COVID-19 hospitalisation; fully adjusted HRs 1.53 (95% CI 1.50 to 1.56) and 1.52 (95% CI 1.46 to 1.56) for adults with asthma prescribed medium and high-dosage ICS, respectively. Risk of hospitalisation was greater for children with asthma prescribed one (2.58 (95% CI 1.82 to 3.66)) or two or more (3.80 (95% CI 2.41 to 5.95)) courses of oral corticosteroids in the year prior to the pandemic. Discussion People with mild and/or well-controlled asthma are neither at significantly increased risk of hospitalisation with nor more likely to die from COVID-19 than adults without asthma.
Serum antiphospholipid antibody status may not be associated with the pregnancy outcomes of patients undergoing in vitro fertilization

Abstract Background: Antiphospholipid syndrome (APS) is an autoimmune disease that is associated with recurrent pregnancy loss. It is still controversial whether the presence of antiphospholipid antibodies (aPL) in the serum of patients with in vitro fertilization-embryo transfer (IVF-ET) has a negative effect on the outcomes. In view of the discrepancies, a meta-analysis of the published data was performed to explore the relationship of aPL and IVF-ET outcomes. Methods: We searched for all published articles indexed in PubMed, Web of Science, and Cochrane Library, which were retrieved up to April, 2021. A total of 921 studies were yielded, of which 6 finally met the inclusion criteria. We carried out the meta-analysis by pooling results of these studies with Review Manager 5.3 software. The effect index was measured with 95% confidence intervals (CIs) of the relative risks (RRs). Results: Six eligible studies were included in this meta-analysis, involving 3214 patients. Our results showed that positive aPL was not associated with decreased clinical pregnancy rate (RR 0.97; 95% CI 0.91-1.04). There was no correlation between positive aPL and increased miscarriage risk (RR 1.22; 95% CI 0.94-1.58). Only 5 of the 6 studies referred to live birth rate, but still no association was found between them (RR 0.95; 95% CI 0.81-1.11). Conclusions: The results showed that the presence of positive aPL neither decreased clinical pregnancy rate and live birth rate, nor increased miscarriage rate in women undergoing IVF, which is differed from the opinion of clinical practice. More prospective studies with high quality and larger sample size are needed to evaluate the relationship between positive aPL and outcomes of IVF-ET.
Diagnostic Accuracy of Urine Lipoarabinomannan Testing in Early Morning Urine versus Spot Urine for Diagnosis of Tuberculosis among People with HIV

This study indicates that FujiLAM testing performs equivalently on spot and early morning urine samples for detecting tuberculosis among people with HIV. Sensitivity could be increased with a two-sample strategy but at the risk of lower specificity. These data can inform future guidelines and clinical practice around FujiLAM. ABSTRACT The Fujifilm SILVAMP TB LAM (FujiLAM) assay offers improved sensitivity compared to Determine TB LAM Ag (AlereLAM) for detecting tuberculosis (TB) among people with HIV. Here, we examined the diagnostic value of FujiLAM testing on early morning urine versus spot urine and the added value of a two-sample strategy. We assessed the diagnostic accuracy of FujiLAM on cryopreserved urine samples collected and stored as part of a prospective cohort of adults with HIV presenting for antiretroviral treatment in Ghana. We compared FujiLAM sensitivity and specificity in spontaneously voided urine samples collected at inclusion (spot urine) versus in the first voided early morning urine (morning urine) and for a one (spot urine) versus two samples (spot and morning urine) strategy. Diagnostic accuracy was determined against both microbiological (using sputum culture and Xpert MTB/RIF testing of sputum and urine to confirm TB) and composite reference standards (including microbiologically confirmed and probable TB cases). Paired urine samples of spot and morning urine were available for 389 patients. Patients had a median CD4 cell count of 176 cells/μL (interquartile range [IQR], 52 to 361). Forty-three (11.0%) had confirmed TB, and 19 (4.9%) had probable TB. Overall agreement for spot versus morning urine test results was 94.6% (kappa, 0.81). Compared to a microbiological reference standard, the FujiLAM sensitivity (95% confidence interval [CI]) was 67.4% (51.5 to 80.9) for spot and 69.8% (53.9 to 82.8) for morning urine, an absolute difference (95% CI) of 2.4% (−10.2 to 14.8). Specificity was 90.2% (86.5 to 93.1) versus 89.0% (85.2 to 92.1) for spot and morning urine, respectively, a difference of 1.2% (−3.7 to 1.4). A two-sample strategy increased FujiLAM sensitivity from 67.4% (51.5 to 80.9) to 74.4% (58.8 to 86.5), a difference of 7.0% (−3.0 to 16.9), while specificity decreased from 90.2% (86.5 to 93.1) to 87.3% (83.3 to 90.6), a difference of −2.9% (−4.9 to −0.8). This study indicates that FujiLAM testing performs equivalently on spot and early morning urine samples. Sensitivity could be increased with a two-sample strategy but at the risk of lower specificity. These data can inform future guidelines and clinical practice. IMPORTANCE This study indicates that FujiLAM testing performs equivalently on spot and early morning urine samples for detecting tuberculosis among people with HIV. Sensitivity could be increased with a two-sample strategy but at the risk of lower specificity. These data can inform future guidelines and clinical practice around FujiLAM.
Dupilumab therapy in atopic dermatitis is safe during COVID‐19 infection era: A systematic review and meta‐analysis of 1611 patients

The aim of this meta‐analysis is to evaluate the safety of dupilumab use in the management of atopic dermatitis (AD) during the current pandemic regarding the risk and the hazards of COVID‐19 infection. Seven databases (Google Scholar, Web of Science, Scopus, Virtual Health Library, PubMed, System for Information on Gray Literature in Europe, and The New York Academy of Medicine) were searched for eligible studies from inception until November 24, 2021. The quality of evidence was rated using the National Institute of Health and the Joanna Briggs Institute Critical Appraisal tool. Meta‐analysis was performed when the outcome is presented ≥2 studies. A total of 12 papers including 1611 AD patients were included in the study. The prevalence of COVID‐19 in AD treated with dupilumab was 3.2% (95% confidence interval [CI]: 1.7–5.8). COVID‐19 symptoms were reported by five patients who were presented with one or more of the following symptoms (fatigue, loss of taste and smell, runny nose, conjunctivitis, gastrointestinal symptoms, fever, cough, and dyspnea). Only three cases of COVID‐19 were hospitalized with a prevalence of 4.5%, while no patients with COVID‐19 died. Dupilumab is safe regarding the risk and the hazards of COVID‐19 in AD patients. Thus, based on these results continuation of dupilumab in AD patients is recommended, since dupilumab seems to be safe and crucial for a better disease outcome.
Weathering the storm alone or together: Examining the impact of COVID‐19 on sole and partnered working mothers

Abstract Sole employed mothers and their families face numerous challenges. Yet, the unprecedented circumstances of the COVID‐19 pandemic may be adding additional risk to the already precarious day‐to‐day reality of this population. Thus, we examine the implications of this crisis for the mental health and job‐related well‐being of both sole and partnered working mothers. Participants were 206 mothers who continued to work during the pandemic. A moderated mediation model was analyzed. Work‐family conflict (WFC) during the pandemic differentially related to mothers’ parenting stress, based on romantic partnership status; when mothers were sole parents, the relationship between WFC and parenting stress was exacerbated. Moreover, this stress mediated the relationship between WFC and both poor mental health and decreased work engagement for sole employed mothers. Findings broaden our understanding of the implications of the COVID‐19 pandemic for sole and partnered employed mothers, and how this crisis may be increasing disparities between working sole‐parent and dual‐partner families.
Clinical application of percutaneous left atrial appendage occlusion guided only by transesophageal echocardiography without fluoroscopy and angiography in the patients with nonvalvular atrial fibrillation

The objective of this study was to understand the clinical efficacy and application of the percutaneous left atrial appendage occlusion (PLAAO) guided only by the transesophageal echocardiography (TEE) in patients with nonvalvular atrial fibrillation (NVAF), without using the fluoroscopy and angiography.
Kingella kingae PilC1 and PilC2 are adhesive multifunctional proteins that promote bacterial adherence, twitching motility, DNA transformation, and pilus biogenesis

The gram-negative bacterium Kingella kingae is a leading cause of osteoarticular infections in young children and initiates infection by colonizing the oropharynx. Adherence to respiratory epithelial cells represents an initial step in the process of K. kingae colonization and is mediated in part by type IV pili. In previous work, we observed that elimination of the K. kingae PilC1 and PilC2 pilus-associated proteins resulted in non-piliated organisms that were non-adherent, suggesting that PilC1 and PilC2 have a role in pilus biogenesis. To further define the functions of PilC1 and PilC2, in this study we eliminated the PilT retraction ATPase in the ΔpilC1ΔpilC2 mutant, thereby blocking pilus retraction and restoring piliation. The resulting strain was non-adherent in assays with cultured epithelial cells, supporting the possibility that PilC1 and PilC2 have adhesive activity. Consistent with this conclusion, purified PilC1 and PilC2 were capable of saturable binding to epithelial cells. Additional analysis revealed that PilC1 but not PilC2 also mediated adherence to selected extracellular matrix proteins, underscoring the differential binding specificity of these adhesins. Examination of deletion constructs and purified PilC1 and PilC2 fragments localized adhesive activity to the N-terminal region of both PilC1 and PilC2. The deletion constructs also localized the twitching motility property to the N-terminal region of these proteins. In contrast, the deletion constructs established that the pilus biogenesis function of PilC1 and PilC2 resides in the C-terminal region of these proteins. Taken together, these results provide definitive evidence that PilC1 and PilC2 are adhesins and localize adhesive activity and twitching motility to the N-terminal domain and biogenesis to the C-terminal domain.