bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amerind ancestry predicts the impact of FADS genetic variation on omega-3 PUFA deficiency, cardiometabolic and inflammatory risk in Hispanic populations
Authors: Yang Chaojie , Hallmark Brian , Chai Jin Choul , O’Connor Timothy D. , Reynolds Lindsay M , Wood Alexis C , Seeds Michael , Chen Yii-Der Ida , Steffen Lyn M , Tsai Michael Y , Kaplan Robert C. , Daviglus Martha L. , Mandarino Lawrence J. , Fretts Amanda M. , Lemaitre Rozenn N , Coletta Dawn K. , Blomquist Sarah A. , Johnstone Laurel M. , Tontsch Chandra , Qi Qibin , Ruczinski Ingo , Rich Stephen S , Mathias Rasika A , Chilton Floyd H , Manichaikul Ani 
Published: April 2021

AbstractHispanic populations have higher rates of obesity, elevated triglycerides, and a greater prevalence of diabetes. Long chain polyunsaturated fatty acids (LC-PUFAs) and LC-PUFA metabolites have critical signaling roles that regulate dyslipidemia and inflammation. Genetic variation in the FADS cluster accounts for a large part of the interindividual differences in circulating and tissue levels of LC-PUFAs, with the genotypes most strongly predictive of low LC-PUFA levels at strikingly higher frequencies in Amerind (AI) ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation, plasma phospholipid levels of LC-PUFAs, anthropometric measures, and circulating metabolic and inflammatory biomarkers in 1,102 Hispanic American participants, representing six distinct ancestry populations from the Multi-Ethnic Study of Atherosclerosis. We demonstrate strong negative associations between AI genetic ancestry and LC-PUFA levels. The FADS rs174537 single nucleotide polymorphism (SNP) accounted for much of the AI ancestry effect on LC-PUFAs, especially for low levels of n-3 LC-PUFAs. Rs174537 was also strongly associated with several metabolic, inflammatory and anthropomorphic traits including circulating triglycerides (TGs) and E-selectin in MESA Hispanics. We further replicated the association with circulating TGs in two additional Hispanic cohorts: the Hispanic Community Health Study/Study of Latinos and the Arizona Insulin Resistance Registry. Our study demonstrates that Amerind ancestry provides a useful and readily available tool to identify individuals most likely to have FADS-related n-3 LC-PUFA deficiencies and associated cardiovascular risk.
Post-treatment downregulation of type III interferons in patients with acute Brucellosis
Authors: Shokri Mehran , Khonakdar Oreinab Ghaffari , Mohammadnia-Afrouzi Mousa , Sadeghi-Haddad-Zavareh Mahmoud , Hasanpour Amirhossein , Barary Mohammad , Ebrahimpour Soheil 
Published: April 2021

AbstractThere is a limited number of clinical studies on interferon (IFN) levels in human brucellosis. The novel group of interferons, type III interferons, consists of four IFN-λ (lambda) molecules called IFN-λ1 or Interleukin-29 (IL-29), IFN-λ2 or IL-28A, IFN-λ3 or IL-28B, and IFN-λ4, are not fully known. This study is one of the first studies of IL-28A and IL-29 levels in Brucellosis cases at the end of their treatment course. A total of 33 acute Brucellosis patients were included in this study. We considered changes in the levels of IL-28A and IL-29 in cases with acute brucellosis before and after treatment with standard therapy that referred to the Ayatollah Rohani Hospital in Babol, Northern Iran. Serum IL-29 and IL-28A (acute form: 56.4 ± 30.32 and 48.73 ± 27.72, respectively, and post-treatment: 40.15 ± 20.30 and 38.79 ± 22.66, respectively) levels were elevated significantly in acute brucellosis than after treatment (p ≤ 0.05). These findings indicate that considering biomarker levels in Brucellosis patients may be indicative of the chronicity of infection. In conclusion, we suggest that IL-29 and IL-28A levels may be valuable biomarkers for follow-up patients with brucellosis.
INTRANASAL APPLICATION OFLACTOCOCCUS LACTIS W 136BACTERIA EARLY IN SARS-Cov-2 INFECTION MAY HAVE A BENEFICIAL IMMUNOMODULATORY EFFECT: A PROOF-OF-CONCEPT STUDY
Authors: Endam Leandra Mfuna , Tremblay Cécile , Filali Ali , Desrosiers Martin Yvon 
Published: April 2021

ABSTRACTJustificationStimulation of early innate anti-viral responses during the early phase of SARS-COV-2 infection oxygen may improve evolution of illness and late pulmonary complications. This may be possible using a TLR agonist such as a probiotic bacterium possessing desirable immunomodulatory properties.MethodWe performed a non-contact, open-label, prospective randomized clinical trial comparing intranasally appliedLactococcus lactis W136with saline irrigation alone in patients within 96 hours of diagnosis of SARS-COV-2 infection not requiring supplemental oxygen.ResultsTwenty-three of a planned forty participants aged 18-59 without comorbidities were recruited. Irrigation with intranasalL lactis W136twice-daily for fourteen days of was associated with a nasal response characterised by increase in the symptom of Facial and Throat pain/discomfort, and with a lesser severity in symptoms of i) Fatigue ii) Olfactory dysfunction and iii) Breathlessness. Safety and tolerability were good, with no acute infections or severe deteriorations.InterpretationFacial and throat pain may correspond to postulated mechanism of action corresponding to activation of innate defences with antiviral effects and may explain the potentially protective effects seen. IntranasalL lactis W136irrigations may thus represent a potentially inexpensive, safe, and easily scalable non-antigen based therapeutic for the continuing global SARS-COV-2 pandemic.Data availability statementData is available on request from the senior author, Dr Desrosiers:martin-yvon.desrosiers.med@ssss.gouv.qc.caFundingThis work was supported with internal funds from the Desrosiers laboratory at the Centre de Recherche du Centre Hospitaller de l’Université de Montreal (CRCHUM).Competing InterestsDr Desrosiers holds equity in Probionase Therapies inc., Which commercialisesLactococcus lactis W136for chronic rhinosinusitis.
Study Pre-protocol for “BronchStart - The Impact of the COVID-19 Pandemic on the Timing, Age and Severity of Respiratory Syncytial Virus (RSV) Emergency Presentations; a Multi-Centre Prospective Observational Cohort Study”
Authors: Williams Thomas C. , Lyttle Mark D , Cunningham Steve , Sinha Ian , Swann Olivia , Maxwell-Hodkinson Abigail , Roland Damian 
Published: April 2021

AbstractBackgroundBronchiolitis (most frequently caused by Respiratory Syncytial Virus; RSV) is a common winter disease predominantly affecting children under one year of age. It is a common reason for presentations to an Emergency Department (ED) and frequently results in hospital admission, contributing to paediatric units approaching or exceeding capacity each winter. During the SARS-CoV-2 pandemic, the circulation of RSV was dramatically reduced in the United Kingdom and Ireland. Evidence from the Southern Hemisphere and other European countries suggests that as social distancing restrictions for SARS-CoV-2 are relaxed, RSV infection returns, causing delayed or even summer epidemics, with different age distributions.Study questionThe ability to track, anticipate and respond to a surge in RSV cases is critical for planning acute care delivery. There is an urgent need to understand the onset of RSV spread at the earliest opportunity. This will influence service planning, to inform clinicians whether the population at risk is a wider age range than normal, and whether there are changes in disease severity. This information is also needed to inform decision on the timing of passive immunisation of children at higher risk of hospitalisation, intensive care admission or death with RSV infection, which is a public health priority.Methods and likely impactThis multi-centre prospective observational cohort study will use a well-established research network (Paediatric Emergency Research in the UK and Ireland, PERUKI) to report in real time cases of RSV infection in children aged under two years, through the collection of essential, but non-identifying patient information. Forty centres will gather initial data on age, index of multiple deprivation quintile, clinical features on presentation, and co-morbidities. Each case will be followed up at 7 days to identify treatment, viral diagnosis and outcome. Information be released on a weekly basis and used to support clinical decision making.
Wood ants express uncertainty when engaging with magnetic cues for directional guidance
Authors: Collett Thomas S. , Philippides Andrew O. 
Published: April 2021

SummaryWood ants were trained indoors to follow a route in a chosen magnetic direction from the centre of a small, circular arena to find a drop of sucrose at the edge. The arena, surrounded by a white cylindrical wall, was in the centre of a 3D coil system that generated an inclined Earth strength magnetic field in any horizontal direction. Between trials, the chosen magnetic training direction was rotated to a new orientation. Tests were given without food and with fresh or reversed paper on the floor of the arena. In a significant number of tests, ants left the centre facing the goal, or in the opposite direction, but they mostly failed to reach the goal. Tests given early in the day, before any training, show that ants remember the magnetic route direction overnight. On some training trials, the position of the sucrose was also indicated by a black stripe. Not uncommonly, ants first moved in the opposite direction to the stripe before switching to the correct direction. Travel away from the reward seems to express the ant’s uncertainty about the correct path to take. Tests show that this uncertainty may stem from competing directional cues linked to the room, suggesting that ants are reluctant to rely on magnetic information alone. We conclude that ants can remember a route direction defined by an Earth-strength magnetic field and that they express any uncertainty about the correct direction by moving for a stretch in the opposite direction. In a second experiment, an upright and an inverted triangle were fixed 90° from each other to the inside of the cylinder. Sucrose was placed beneath one of the triangles, dependent on the direction of the magnetic field. Ants failed to master this task and to approach the magnetically cued triangle. Instead, they preferred to approach the upright triangle. The ants were again uncertain of the correct direction and expressed this uncertainty through paths that had segments directed towards both the inverted and the upright triangles.
Dimensionality reduction for neural population decoding
Authors: Heller Charles R. , David Stephen V. 
Published: April 2021

AbstractRapidly developing technology for large scale neural recordings has allowed researchers to measure the activity of hundreds to thousands of neurons at single cell resolutionin vivo. Neural decoding analyses are a widely used tool used for investigating what information is represented in this complex, high-dimensional neural population activity. Most population decoding methods assume that correlated activity between neurons has been estimated accurately. In practice, this requires large amounts of data, both across observations and across neurons. Unfortunately, most experiments are fundamentally constrained by practical variables that limit the number of times the neural population can be observed under a single stimulus and/or behavior condition. Therefore, new analytical tools are required to study neural population coding while taking into account these limitations. Here, we present a simple and interpretable method for dimensionality reduction that allows neural decoding metrics to be calculated reliably, even when experimental trial numbers are limited. We illustrate the method using simulations and compare its performance to standard approaches for dimensionality reduction and decoding by applying it to single-unit electrophysiological data collected from auditory cortex.
Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis
Authors: Vastrad Basavaraj , Vastrad Chanabasayya 
Published: April 2021

AbstractTo provide a better understanding of dementia at the molecular level, this study aimed to identify the genes and key pathways associated with dementia by using integrated bioinformatics analysis. Based on the expression profiling by high throughput sequencing dataset GSE153960 derived from the Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) between patients with dementia and healthy controls were identified. With DEGs, we performed a series of functional enrichment analyses. Then, a protein–protein interaction (PPI) network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network was constructed, analyzed and visualized, with which the hub genes miRNAs and TFs nodes were screened out. Finally, validation of hub genes was performed by using receiver operating characteristic curve (ROC) analysis. A total of 948 DEGs were screened out, among which 475 genes were up regulated; while 473 were down regulated. Functional enrichment analyses indicated that DEGs were mainly involved in defense response, ion transport, neutrophil degranulation and neuronal system. The hub genes (CDK1, TOP2A, MAD2L1, RSL24D1, CDKN1A, NOTCH3, MYB, PWP2, WNT7B and HSPA12B) were identified from PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network. We identified a series of key genes along with the pathways that were most closely related with dementia initiation and progression. Our results provide a more detailed molecular mechanism for the advancement of dementia, shedding light on the potential biomarkers and therapeutic targets.
Early treatment with nitazoxanide prevents worsening of mild and moderate COVID-19 and subsequent hospitalization
Authors: Rossignol Jean-François , Matthew C. Bardin , Oaks Joshua B. , Bostick B. Gregory , Vora Kishor N. , Fulgencio Jessica , Mogelnicki Dena , Bréchot Christian ,   Vanguard Study Group
Published: April 2021

AbstractBackgroundThere is an urgent need for treatments to prevent the progression to severe COVID-19 and hospitalization.MethodsA randomized double-blind placebo-controlled clinical trial in 36 centers in the U.S. and Puerto Rico investigated the safety and effectiveness of oral nitazoxanide 600 mg twice daily for 5 days in outpatients with symptoms of mild or moderate COVID-19 enrolled within 72 hours of symptom onset. Key objectives were reduction of duration of symptoms (primary) and progression to severe illness (key secondary).Results1,092 subjects were enrolled, and 379 with laboratory-confirmed SARS-CoV-2 infection were analyzed. Overall, times to sustained clinical recovery were similar for the two arms. Nitazoxanide treatment was associated with an 85% reduction in the progression to severe COVID-19 (1/184, [0.5%] vs. 7/195, [3.6%], p=0.07) and 82% reduction in the rate of hospitalization, emergency room visit or death (1/184 [0.5%] vs. 6/195 [3.1%], p=0.12). In subjects with mild illness at baseline, treatment was also associated with a 3.1-day reduction in median time to sustained clinical recovery and a 5.2-day reduction in time to return to usual health. Nitazoxanide was safe and well tolerated.ConclusionsTreatment of mild or moderate COVID-19 with a five-day course of oral nitazoxanide was safe and well tolerated and was associated with an 85% reduction in the progression to severe illness and a 3- to 5-day reduction of the duration of mild illness.
Silver diamine fluoride, atraumatic restorations, and oral health-related quality of life - Results from the CariedAway cluster randomized trial
Authors: Ruff Ryan Richard , Barry Godín Tamarinda J. , Small Topaz Murray , Niederman Richard 
Published: April 2021

AbstractObjectiveSilver diamine fluoride (SDF) is a non-surgical treatment for the arrest and prevention of dental caries that results in irreversible black staining of dental decay. The objective of this study was to evaluate the impact of SDF treatment on oral health-related quality of life (OHRQoL) relative to a standard package of glass ionomer sealants and atraumatic restorative treatment.MethodsCariedAway is a pragmatic, longitudinal, cluster-randomized non-inferiority trial of non-surgical interventions for caries. Secondary study outcomes included OHRQoL and academic performance. Oral health-related quality of life was measured at each study visit using the Child Oral Health Impact Profile. Change in OHRQoL was assessed using linear regression and non-inferiority was determined using t-tests.ResultsUntreated decay at baseline was associated with signifcantly worse ORHQoL and treatment in both groups resulted in incremental improvement. Quality of life in children receiving silver diamine fluoride was non-inferior to those receiving sealants and ART at least six months post-treatment. Additionally, change in OHRQoL did not depend on the severity of baseline decay.ConclusionsORHQoL is related to untreated dental caries, however no appreciable change was observed following SDF treatment relative to standard preventive therapies.
Identification of Key Influencers for Secondary Distribution of HIV Self-Testing among Chinese MSM: A Machine Learning Approach
Authors: Jing Fengshi , Ye Yang , Zhou Yi , Ni Yuxin , Yan Xumeng , Lu Ying , Ong Jason J , Tucker Joseph D , Wu Dan , Xiong Yuan , Xu Chen , He Xi , Huang Shanzi , Li Xiaofeng , Jiang Hongbo , Wang Cheng , Dai Wencan , Huang Liqun , Mei Wenhua , Cheng Weibin , Zhang Qingpeng , Tang Weiming 
Published: April 2021

AbstractBackgroundHIV self-testing (HIVST) has been rapidly scaled up and additional strategies further expand testing uptake. Secondary distribution has people (indexes) apply for multiple kits and pass these kits to people (alters) in their social networks. However, identifying key influencers is difficult. This study aimed to develop an innovative ensemble machine learning approach to identify key influencers among Chinese men who have sex with men (MSM) for HIVST secondary distribution.MethodWe defined three types of key influencers: 1) key distributors who can distribute more kits; 2) key promoters who can contribute to finding first-time testing alters; 3) key detectors who can help to find positive alters. Four machine learning models (logistic regression, support vector machine, decision tree, random forest) were trained to identify key influencers. An ensemble learning algorithm was adopted to combine these four models. Simulation experiments were run to validate our approach.Results309 indexes distributed kits to 269 alters. Our approach outperformed human identification (self-reported scales cut-off), exceeding by an average accuracy of 11·0%, could distribute 18·2% (95%CI: 9·9%-26·5%) more kits, find 13·6% (95%CI: 1·9%-25·3%) more first-time testing alters and 12·0% (95%CI: -14·7%-38·7%) more positive-testing alters. Our approach could also increase simulated intervention efficiency by 17·7% (95%CI: -3·5%-38·8%) than human identification.ConclusionWe built machine learning models to identify key influencers among Chinese MSM who were more likely to engage in HIVST secondary distribution.Key Findings (can also be found in Figure.2-Infographic)Our proposed ensemble machine learning approach outperformed human identification (self-reported scales cut-off) in accuracy & F1 by classification metrics and in intervention efficiency by simulation experiments. Our model could also distribute more kits, find more first-time/positive-testing alters than human identification.
CFHloss in human RPE cells leads to inflammation and complement system dysregulationviathe NF-κB pathway
Authors: Armento Angela , Schmidt Tiziana L , Sonntag Inga , Merle David , Jarboui Mohamed Ali , Kilger Ellen , Clark Simon J. , Ueffing Marius 
Published: April 2021

AbstractAge-related macular degeneration (AMD), the leading cause of vision loss in the elderly, is a degenerative disease of the macula, where retinal pigment epithelium (RPE) cells are damaged in the early stages of the disease and chronic inflammatory processes may be involved. Besides ageing and lifestyle factors as drivers of AMD, a strong genetic association to AMD is found in genes of the complement system, with a single polymorphism in the complement factor H gene (CFH), accounting for the majority of AMD risk. However, the exact mechanism by whichCFHdysregulation confers such a great risk for AMD and its role in RPE cells homeostasis is unclear. To explore the role of endogenousCFHlocally in RPE cells, we silencedCFHin human hTERT-RPE1 cells. We demonstrate that endogenously expressedCFHin RPE cells modulates inflammatory cytokine production and complement regulation, independent of external complement sources or stressors. We show that loss of the factor H protein (FH) results in increased levels of inflammatory mediators (e.g. IL-6, IL-8, GM-CSF) and altered levels of complement proteins (e.g. C3, CFBupregulation andC5downregulation) that are known to play a role in AMD. Moreover, we identified the NF-κB pathway as the major pathway involved in the regulation of these inflammatory and complement factors. Our findings suggest that in RPE cells, FH and the NF-κB pathway work in synergy to maintain inflammatory and complement balance and in case either one of them is dysregulated, the RPE microenvironment changes towards a pro-inflammatory AMD-like phenotype.
Perfecting and extending the near-infrared biological window
Authors: Feng Zhe , Tang Tao , Wu Tianxiang , Yu Xiaoming , Zhang Yuhuang , Wang Meng , Zheng Junyan , Ying Yanyun , Chen Siyi , Zhou Jing , Fan Xiaoxiao , Li Shengliang , Zhang Mingxi , Qian Jun 
Published: April 2021

AbstractIn vivofluorescence imaging in the second near-infrared window (NIR-II) has been considered as a promising technique for visualizing the mammals. However, the definition of the NIR-II region and the mechanism accounting for the excellent performance still need to be perfected. Herein, we simulated bioimaging in the NIR spectral range (to 2340 nm), confirmed the positive contribution of moderate light absorption by water in intravital imaging and perfected the NIR-II window as 900-1880 nm, where the 1400-1500 nm was defined as NIR-IIx region and the 1700-1880 nm was defined as NIR-IIc region, respectively. Moreover, the 2080-2340 nm was newly proposed as the third near-infrared (NIR-III) window, which was believed to provide the best imaging quality. The wide-field fluorescence microscopy in brain, in addition, was performed around NIR-IIx region with excellent optical sectioning strength and the largest imaging depth of in vivo NIR-II fluorescence microscopy to date. We also proposed 1400 nm long-pass detection in off-peak NIR-II imaging whose profits exceeded those of NIR-IIb imaging, using bright fluorophores with short peak emission wavelength.