bluuebunny/crossref_metadata_2025_split huggingface dataset:
Convergent antibody responses are associated with broad neutralization of hepatitis C virus
Authors: Skinner Nicole E. , Ogega Clinton O. , Frumento Nicole , Clark Kaitlyn E. , Paul Harry , Yegnasubramanian Srinivasan , Schuebel Kornel , Meyers Jennifer , Gupta Anuj , Wheelan Sarah , Cox Andrea L. , Crowe James E. , Ray Stuart C. , Bailey Justin R. 
Published: March 2023

IntroductionEarly development of broadly neutralizing antibodies (bNAbs) targeting the hepatitis C virus (HCV) envelope glycoprotein E2 is associated with spontaneous clearance of infection, so induction of bNAbs is a major goal of HCV vaccine development. However, the molecular antibody features important for broad neutralization are not known.MethodsTo identify B cell repertoire features associated with broad neutralization, we performed RNA sequencing of the B cell receptors (BCRs) of HCV E2-reactive B cells of HCV-infected individuals with either high or low plasma neutralizing breadth. We then produced a monoclonal antibody (mAb) expressed by pairing the most abundant heavy and light chains from public clonotypes identified among clearance, high neutralization subjects.ResultsWe found distinctive BCR features associated with broad neutralization of HCV, including long heavy chain complementarity determining region 3 (CDRH3) regions, specific VH gene usage, increased frequencies of somatic hypermutation, and particular VH gene mutations. Most intriguing, we identified many E2-reactive public BCR clonotypes (heavy and light chain clones with the same V and J-genes and identical CDR3 sequences) present only in subjects who produced highly neutralizing plasma. The majority of these public clonotypes were shared by two subjects who cleared infection. A mAb expressing the most abundant public heavy and light chains from these clearance, high neutralization subjects had features enriched in high neutralization clonotypes, such as increased somatic hypermutation frequency and usage of IGHV1-69, and was cross-neutralizing.DiscussionTogether, these results demonstrate distinct BCR repertoires associated with high plasma neutralizing capacity. Further characterization of the molecular features and function of these antibodies can inform HCV vaccine development.
Two new siderophores produced by Pseudomonas sp. NCIMB 10586: The anti-oomycete non-ribosomal peptide synthetase-dependent mupirochelin and the NRPS-independent triabactin
Authors: Grosse Camille , Brandt Nathalie , Van Antwerpen Pierre , Wintjens René , Matthijs Sandra 
Published: March 2023

IntroductionGlobisporangium ultimum is an oomycetal pathogen causing damping-off on over 300 different plant hosts. Currently, as for many phytopathogens, its control relies in the use of chemicals with negative impact on health and ecosystems. Therefore, many biocontrol strategies are under investigation to reduce the use of fungicides.ResultsIn this study, the soil bacterium Pseudomonas sp. NCIMB 10586 demonstrates a strong iron-repressed in vitro antagonism against G. ultimum MUCL 38045. This antagonism does not depend on the secretion of the broad-range antibiotic mupirocin or of the siderophore pyoverdine by the bacterial strain. The inhibitor molecule was identified as a novel non-ribosomal peptide synthetase (NRPS) siderophore named mupirochelin. Its putative structure bears similarities to other siderophores and bioactive compounds. The transcription of its gene cluster is affected by the biosynthesis of pyoverdine, the major known siderophore of the strain. Besides mupirochelin, we observed the production of a third and novel NRPS-independent siderophore (NIS), here termed triabactin. The iron-responsive transcriptional repression of the two newly identified siderophore gene clusters corroborates their role as iron scavengers. However, their respective contributions to the strain fitness are dissimilar. Bacterial growth in iron-deprived conditions is greatly supported by pyoverdine production and, to a lesser extent, by triabactin. On the contrary, mupirochelin does not contribute to the strain fitness under the studied conditions.ConclusionAltogether, we have demonstrated here that besides pyoverdine, Pseudomonas sp. NCIMB 10586 produces two newly identified siderophores, namely mupirochelin, a weak siderophore with strong antagonism activity against G. ultimum, and the potent siderophore triabactin.
Detecting changes in the blood flow of the optic disk in patients with nonarteritic anterior ischemic optic neuropathy via optical coherence tomography–angiography
Authors: Xiao Qing , Sun Chuan-bin 
Published: March 2023

PurposeThis study aimed to evaluate the changes in the blood flow of the optic disk in patients with nonarteritic anterior ischemic optic neuropathy (NAION) using optical coherence tomography–angiography (OCTA) and to investigate the relationship among the changes in the blood flow of the optic disk, visual field defect, peripapillary retinal nerve fiber layer (RNFL), and macular ganglion cell complex (mGCC).MethodsThis was a prospective observational case series study. A total of 89 patients (89 eyes) with NAION were included in this study. All patients underwent best corrected visual acuity (BCVA), slit-lamp and direct ophthalmoscopic examinations, color fundus photography, visual field test, and blood flow indicators of the radial peripapillary capillaries (RPC) including whole en face image vessel density (VD), peripapillary VD by OCTA, the peripapillary RNFL, and mGCC by spectral-domain optic coherence tomography (OCT). The changes of blood flow in the optic disk at ≤3, 4–8, 9–12, 13–24, and &gt;24 weeks of the natural course of NAION were measured, and the relationship among the changes in the blood flow of the optic disk, visual field defect, peripapillary RNFL, and mGCC was also analyzed.ResultsThe mean age of 89 patients with NAION was 56.42 ± 6.81 years (ranging from 39 to 79). The initial RPC whole en face image VD was significantly reduced after acute NAION (≤3 weeks) (F = 45.598, P &lt; 0.001) and stabilized from the eighth week onward. Over the course of NAION, the superonasal RPC, superior mGCC, and superotemporal RNFL decreased mostly with time (F = 95.658, 109.787, 263.872, respectively; P &lt; 0.001). Maximal correlations were found between superior mGCC and temporosuperior RPC in the NAION phase (R = 0.683, P &lt; 0.01) and between superonasal RPC and superonasal RNFL (R = 0.740, P &lt; 0.01). The mean defect was correlated with temporosuperior RPC (R = −0.281, P &lt; 0.01) and superior mGCC (R = −0.160, P = 0.012).ConclusionOver the course of NAION, OCTA shows a tendency toward change in the retinal capillary plexus of the optic disk. OCTA is proved to be a practical and useful tool for observing papillary perfusion in NAION.
microRNA 146a ameliorates retinal damage in experimental autoimmune uveitis
Authors: Saraswathy Sindhu , Rao Narsing A. 
Published: March 2023

IntroductionUveitis and related intraocular inflammations are a major cause of blindness due to retinal damage caused by degeneration and loss of the photoreceptor cells. In mouse experimental autoimmune uveitis (EAU) previously we have shown mitochondrial oxidative stress with marked upregulation of αA crystallin in the inner segments of the photoreceptors. Furthermore, αA crystallin treatment prevented photoreceptor mitochondrial oxidative stress by suppressing innate and adaptive immunity in EAU.MethodsSince these immune processes are modulated by microRNAs, in this study we investigated (a) modulation of microRNAs during development of EAU by αA crystallin administration and (b) microRNA therapeutic intervention.ResultsFew microRNAs were significantly upregulated in EAU mice with intravenous injection of αA crystallin and among these, computational bioinformatic analysis revealed that the upregulated microRNA 146a targets the innate and adaptive immune responses. In EAU, intravenous as well as intravitreal administration of this microRNA prevented inflammatory cell infiltration in uvea and retina and preserved photoreceptor cells.DiscussionThis protective function suggests that microRNA146a can be a novel therapeutic agent in preventing retinal damage in uveitis.
Hsa-miR-323a-3p functions as a tumor suppressor and targets STAT3 in neuroblastoma cells
Authors: Bhavsar Swapnil Parashram , Olsen Lotte , Løkke Cecilie , Koster Jan , Flægstad Trond , Einvik Christer 
Published: March 2023

BackgroundStudies conducted in the last decades have revealed a role for the non-coding microRNAs (miRNAs) in cancer development and progression. Several miRNAs within the chromosome region 14q32, a region commonly deleted in cancers, are associated with poor clinical outcome in the childhood cancer neuroblastoma. We have previously identified miR-323a-3p from this region to be downregulated in chemotherapy treated neuroblastoma cells compared to pre-treatment cells from the same patients. Furthermore, in neuroblastoma tumors, this miRNA is downregulated in advanced stage 4 disease compared to stage 1–2. In this study, we attempt to delineate the unknown functional roles of miR-323a-3p in neuroblastoma.MethodsSynthetic miRNA mimics were used to overexpress miR-323a-3p in neuroblastoma cell lines. To investigate the functional roles of miR-323a-3p, cell viability assay, flow cytometry, reverse transcription-quantitative polymerase chain reaction, luciferase reporter assay and western blot were conducted on the neuroblastoma cell lines Kelly, SH-SY5Y and SK-N-BE(2)-C.ResultsEctopic expression of miR-323a-3p resulted in marked reduction of cell viability in Kelly, SH-SY5Y and SK-N-BE(2)-C by causing G1-cell cycle arrest in Kelly and SH-SY5Y and apoptosis in all the cell lines tested. Furthermore, mRNA and protein levels of signal transducer and activator of transcription 3 (STAT3) were reduced upon miR-323a-3p overexpression. A direct binding of the miR-323a-3p to the 3′UTR of STAT3 was experimentally validated by luciferase reporter assay, where miR-323a-3p reduced luminescent signal from full length STAT3 3′UTR luciferase reporter, but not from a reporter with mutation in the predicted seed sequence.ConclusionsmiR-323a-3p inhibits growth of neuroblastoma cell lines through G1-cell cycle arrest and apoptosis, and the well-known oncogene STAT3 is a direct target of this miRNA.
No association between thickening fraction of the diaphragm and extubation success in ventilated children
Authors: Duyndam Anita , Smit Joke , Houmes Robert Jan , Heunks Leo , Molinger Jeroen , IJland Marloes , van Rosmalen Joost , van Dijk Monique , Tibboel Dick , Ista Erwin 
Published: March 2023

IntroductionIn mechanically ventilated adults, thickening fraction of diaphragm (dTF) measured by ultrasound is used to predict extubation success. Whether dTF can also predict extubation success in children is unclear.AimTo investigate the association between dTF and extubation success in children. Second, to assess diaphragm thickness during ventilation and the correlation between dTF, diaphragm thickness (Tdi), age and body surface.MethodProspective observational cohort study in children aged 0–18 years old with expected invasive ventilation for &gt;48 h. Ultrasound was performed on day 1 after intubation (baseline), day 4, day 7, day 10, at pre-extubation, and within 24 h after extubation. Primary outcome was the association between dTF pre-extubation and extubation success. Secondary outcome measures were Tdi end-inspiratory and Tdi end-expiratory and atrophy defined as &lt;10% decrease of Tdi end-expiratory versus baseline at pre-extubation. Correlations were calculated with Spearman correlation coefficients. Inter-rater reliability was calculated with intraclass correlation (ICC).ResultsFifty-three patients, with median age 3.0 months (IQR 0.1–66.0) and median duration of invasive ventilation of 114.0 h (IQR 55.5–193.5), were enrolled. Median dTF before extubation with Pressure Support 10 above 5 cmH2O was 15.2% (IQR 9.7–19.3). Extubation failure occurred in six children, three of whom were re-intubated and three then received non-invasive ventilation. There was no significant association between dTF and extubation success; OR 0.33 (95% CI; 0.06–1.86). Diaphragmatic atrophy was observed in 17/53 cases, in three of extubation failure occurred. Children in the extubation failure group were younger: 2.0 months (IQR 0.81–183.0) vs. 3.0 months (IQR 0.10–48.0); p = 0.045. At baseline, pre-extubation and post-extubation there was no significant correlation between age and BSA on the one hand and dTF, Tdi- insp and Tdi-exp on the other hand. The ICC representing the level of inter-rater reliability between the two examiners performing the ultrasounds was 0.994 (95% CI 0.970–0.999). The ICC of the inter-rater reliability between the raters in 36 paired assessments was 0.983 (95% CI 0.974–0.990).ConclusionThere was no significant association between thickening fraction of the diaphragm and extubation success in ventilated children.
Efficacy and safety of Melaleuca alternifolia (tea tree) oil for human health—A systematic review of randomized controlled trials
Authors: Kairey Lana , Agnew Tamara , Bowles Esther Joy , Barkla Bronwyn J. , Wardle Jon , Lauche Romy 
Published: March 2023

Introduction: Leaves of the Australian tea tree plant Melaleuca alternifolia were used traditionally by First Nations Australians for treating wounds, burns, and insect bites. Tea tree oil, the essential oil steam-distilled from M. alternifolia, is well-known for its medicinal properties, the evidence for most applications however is limited. This review aimed to critically appraise evidence from clinical trials examining the therapeutic efficacy and safety of tea tree oil on outcomes.Methods: Randomized controlled trials with participants of any age, gender, or health status, comparing tea tree oil to any control were included, without limit on publication date. Electronic databases were searched on 12 August 2022 with additional records sourced from article reference sections, reviews, and industry white papers. Risk of bias was assessed by two authors independently using the Cochrane risk-of-bias 1.0 tool. Results were summarized and synthesized thematically.Results: Forty-six articles were eligible from the following medical fields (Dentistry n = 18, Dermatology n = 9, Infectious disease n = 9, Ophthalmology n = 6, Podiatry n = 3; and Other n = 1). Results indicate that oral mouthwashes with 0.2%–0.5% tea tree oil may limit accumulation of dental plaque. Gels containing 5% tea tree oil applied directly to the periodontium may aid treatment of periodontitis as an adjunctive therapy to scaling and root planing. More evidence is needed to confirm the benefits of tea tree oil for reducing acne lesions and severity. Local anti-inflammatory effects on skin, if any, also require further elucidation. Topical tea tree oil regimens show similar efficacy to standard treatments for decolonizing the body from methicillin-resistant Staphylococcus aureus, although intra-nasal use of tea tree oil may cause irritation to mucous membranes. Tea tree oil with added iodine may provide an effective treatment for molluscum contagiosum lesions in young children. More evidence on efficacy of tea tree oil-based eyelid wipes for Demodex mite control are needed. Side effects were reported in 60% of included studies and were minor, except where tea tree oil was applied topically in concentrations ≥ 25%.Discussion: Overall, the quality of research was poor to modest and higher quality trials with larger samples and better reporting are required to substantiate potential therapeutic applications of tea tree oil.Systematic Review Registration: PROSPERO, identifier [CRD42021285168].
Metabolite-assisted models improve risk prediction of coronary heart disease in patients with diabetes
Authors: Shen Min , Xie Qingya , Zhang Ruizhe , Yu Chunjing , Xiao Pingxi 
Published: March 2023

Background: Patients with diabetes have a two-to four-fold increased incidence of cardiovascular diseases compared with non-diabetics. Currently, there is no recognized model to predict the occurrence and progression of CVDs in diabetics.Objective: This work aimed to develop a metabolic biomarker-assisted model, a combination of metabolic markers with clinical variables, for risk prediction of CVDs in diabetics.Methods: A total of 475 patients with diabetes were studied. Each patient underwent coronary angiography. Plasma samples were analyzed by liquid chromatography-quadrupole time-of-flight mass spectrometry. Ordinal logistic regression and random forest were used to screen metabolites. Receiver operating characteristic (ROC) curve, nomogram, and decision curve analysis (DCA) were employed to evaluate their prediction performances.Results: Ordinal logistic regression screened out 34 differential metabolites (adjusted-false discovery rate p &lt; 0.05) from 2059 ion features by comparisons of diabetics with and without CVDs. Random forest identified methylglutarylcarnitine and lysoPC (18:0) as the metabolic markers (mean decrease gini &gt;1.0) for non-significant CVDs (nos-CVDs) versus normal coronary artery (NCA), 1,3-Octadiene and 3-Octanone for acute coronary syndrome (ACS) versus nos-CVDs, and lysoPC (18:0) for acute coronary syndrome versus normal coronary artery. For risk prediction, the metabolic marker-assisted models provided areas under the curve of 0.962–0.979 by ROC (0.576–0.779 for the base models), and c-indices of 0.8477–0.9537 by nomogram analysis (0.1514–0.5196 for the base models). Decision curve analysis (DCA) showed that the models produced greater benefits throughout a wide range of risk probabilities compared with the base model.Conclusion: Metabolic biomarker-assisted model remarkably improved risk prediction of cardiovascular disease in diabetics (&gt;90%).
Indexing hematological and serum biochemical reference intervals of Himalayan snow trout, Schizothorax esocinus to instrument in health assessment
Authors: Reshi Quseen Mushtaq , Ahmed Imtiaz , Al-Anazi Khalid Mashay , Farah Mohammad Abul 
Published: March 2023

Schizothorax esocinus, commonly known as snow trout, is one of the main contributors of food and livelihood in the colder zone of Himalayan region. The comprehensive information on its hematological and serum biochemical reference intervals is not reported yet. In the present study an attempt has been made to elucidate the hematological and serum biochemical reference intervals of S. esocinus from River Jhelum using protocols of the American Society of Veterinary Clinical Pathology (ASVCP). Wild fish were sampled over a period of 2 years from the pollution free sites of river Jhelum. Fish blood was harvested through caudal venipuncture and hemato-biochemical analysis performed thereof. Data values from a total of healthy 432 adult fish specimens (216 male, 216 female) were systematically recorded. The reference intervals for hematological and serum biochemical parameters of S. esocinus were established using Reference Value Advisor software v 2.1. RIs for hematological and serum analytes ranged as: hemoglobin (Hb) 78.38–116.35 (g/L); white blood cells (WBC) 10–20 (×109/L); red blood cells (RBC) 1.30–2.15 (×1012/L); packed cell volume 27.00–39.45 (%); total protein 39.21–61.62 (g/L); albumin 8.20–22.02 (g/L); globulin 27.58–49.55 (g/L); glucose 3.25–7.18 (mmol/L); urea 0.96—2.38 (mmol/L); cholesterol 3.80–6.90 (mmol/L). The study also depicted that certain blood measurands were influenced with respect to sex. Significantly (p &lt; 0.05) higher values of Hb, red blood cells count and serum glucose were noted in male as compared to female which, on the other hand, registered higher white blood cells count and serum cholesterol level (Mann Whitney U test, p &lt; 0.05). The work, therefore, provides baseline information on hematological and serum biochemical analytes of this species which holds high commercial importance. RIs reported here can help monitor the health status of fish by improving the use of non-lethal diagnostic methods in piscine medicine.
A systematic scoping review on the evidence behind debriefing practices for the wellbeing/emotional outcomes of healthcare workers
Authors: Evans Thomas Rhys , Burns Calvin , Essex Ryan , Finnerty Gina , Hatton Ella , Clements Andrew James , Breau Genevieve , Quinn Francis , Elliott Helen , Smith Lorraine D. , Matthews Barry , Jennings Kath , Crossman Jodie , Williams Gareth , Miller Denise , Harold Benjamin , Gurnett Philip , Jagodzinski Lee , Smith Julie , Milligan Wendy , Markowski Marianne , Collins Peter , Yoshimatsu Yuki , Margalef Turull Jordi , Colpus Mark , Dayson Mark L. , Weldon Sharon 
Published: March 2023

IntroductionDebriefings give healthcare workers voice through the opportunity to discuss unanticipated or difficult events and recommend changes. The typical goal of routine debriefings has been to improve clinical outcomes by learning through discussion and reflection of events and then transferring that learning into clinical practice. However, little research has investigated the effects of debriefings on the emotional experiences and well-being of healthcare workers. There is some evidence that debriefings are a multi-faceted and cost-effective intervention for minimising negative health outcomes, but their use is inconsistent and they are infrequently adopted with the specific intention of giving healthcare workers a voice. The purpose of this systematic scoping review is therefore to assess the scope of existing evidence on debriefing practices for the well-being and emotional outcomes of healthcare workers.MethodsFollowing screening, 184 papers were synthesised through keyword mapping and exploratory trend identification.ResultsThe body of evidence reviewed were clustered geographically, but diverse on many other criteria of interest including the types of evidence produced, debriefing models and practices, and outcomes captured.DiscussionThe current review provides a clear map of our existing understanding and highlights the need for more systematic, collaborative and rigorous bodies of evidence to determine the potential of debriefing to support the emotional outcomes of those working within healthcare.Systematic Review Registrationhttps://osf.io/za6rj.