bluuebunny/crossref_metadata_2025 huggingface dataset:
Virologic and immunologic outcomes of treatment with integrase inhibitors in a real-world setting: The RESPOND cohort consortium
Authors: Neesgaard Bastian , Mocroft Amanda , Zangerle Robert , Wit Ferdinand , Lampe Fiona , Günthard Huldrych F. , Necsoi Coca , Law Matthew , Mussini Cristina , Castagna Antonella , Monforte Antonella d’Arminio , Pradier Christian , Chkhartisvilli Nikoloz , Reyes-Uruena Juliana , Vehreschild Jörg Janne , Wasmuth Jan-Christian , Sönnerborg Anders , Stephan Christoph , Greenberg Lauren , Llibre Josep M. , Volny-Anne Alain , Peters Lars , Pelchen-Matthews Annegret , Vannappagari Vani , Gallant Joel , Rieger Armin , Youle Mike , Braun Dominique , De Wit Stephane , Petoumenos Kathy , Borghi Vanni , Spagnuolo Vincenzo , Tsertsvadze Tengiz , Lundgren Jens , Ryom Lene ,   for The RESPOND study group
Published: December 2020

Objectives

To compare virologic and immunologic outcomes of integrase inhibitor (INSTI)-containing, contemporary boosted protease inhibitor (PI/b)-containing and non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens in a real-life setting.

Methods

Using logistic regression, virologic and immunologic outcomes of INSTI use were compared to outcomes of PI/b or NNRTI treatment 12 months after treatment start or switch, for participants in the RESPOND cohort consortium. A composite treatment outcome (cTO) was used, defining success as viral load (VL) <200 copies/mL and failure as at least one of: VL ≥200 copies/mL, unknown VL in the time window, any changes of antiretroviral therapy (ART) regimen, AIDS, or death. In addition, on-treatment analysis including only individuals with known VL and no regimen changes was performed. Favorable immunologic response was defined as a 25% increase in CD4 count or as reaching ≥750 CD4 cells/μL.

Results

Between January 2012 and January 2019, 13,703 (33.0% ART-naïve) individuals were included, of whom 7,147 started/switched to a regimen with an INSTI, 3,102 to a PI/b and 3,454 to an NNRTI-containing regimen. The main reason for cTO failure in all treatment groups were changes in ART regimen. Compared to INSTIs, the adjusted odds ratio (aOR) of cTO success was significantly lower for PI/b (0.74 [95% confidence interval, CI 0.67–0.82], p <0.001), but similar for NNRTIs (1.07 [CI 0.97–1.17], p = 0.11). On-treatment analysis and sensitivity analyses using a VL cut-off of 50 copies/mL were consistent. Compared to INSTIs, the aORs of a 25% increase in CD4 count were lower for NNRTIs (0.80 [CI 0.71–0.91], p<0.001) and PI/b (0.87 [CI 0.76–0.99], p = 0.04).

Conclusion

In this large analysis of a real-world population, cTO and on-treatment success were similar between INSTIs and NNRTIs, but lower for PI/b, though residual confounding cannot be fully excluded. Obtaining favorable immunologic outcomes were more likely for INSTIs than the other drug classes.
Reconfiguration of the cortical-hippocampal interaction may compensate for Sharp-Wave Ripple deficits in APP/PS1 mice and support spatial memory formation
Authors: Jura Bartosz , Młoźniak Dariusz , Goszczyńska Hanna , Blinowska Katarzyna , Biendon Nathalie , Macrez Nathalie , Meyrand Pierre , Bem Tiaza
Published: December 2020

Hippocampal-cortical dialogue, during which hippocampal ripple oscillations support information transfer, is necessary for long-term consolidation of spatial memories. Whereas a vast amount of work has been carried out to understand the cellular and molecular mechanisms involved in the impairments of memory formation in Alzheimer’s disease (AD), far less work has been accomplished to understand these memory deficiencies at the network-level interaction that may underlie memory processing. We recently demonstrated that freely moving 8 to 9-month-old APP/PS1 mice, a model of AD, are able to learn a spatial reference memory task despite a major deficit in Sharp-Wave Ripples (SWRs), the integrity of which is considered to be crucial for spatial memory formation. In order to test whether reconfiguration of hippocampal-cortical dialogue could be responsible for the maintenance of this ability for memory formation, we undertook a study to identify causal relations between hippocampal and cortical circuits in epochs when SWRs are generated in hippocampus. We analyzed the data set obtained from multielectrode intracranial recording of transgenic and wild-type mice undergoing consolidation of spatial memory reported in our previous study. We applied Directed Transfer Function, a connectivity measure based on Granger causality, in order to determine effective coupling between distributed circuits which express oscillatory activity in multiple frequency bands. Our results showed that hippocampal-cortical coupling in epochs containing SWRs was expressed in the two frequency ranges corresponding to ripple (130–180 Hz) and slow gamma (20–60 Hz) band. The general features of connectivity patterns were similar in the 8 to 9-month-old APP/PS1 and wild-type animals except that the coupling in the slow gamma range was stronger and spread to more cortical sites in APP/PS1 mice than in the wild-type group. During the occurrence of SWRs, the strength of effective coupling from the cortex to hippocampus (CA1) in the ripple band undergoes sharp increase, involving cortical areas that were different in the two groups of animals. In the wild-type group, retrosplenial cortex and posterior cingulate cortex interacted with the hippocampus most strongly, whereas in the APP/PS1 group more anterior structures interacted with the hippocampus, that is, anterior cingulate cortex and prefrontal cortex. This reconfiguration of cortical-hippocampal interaction pattern may be an adaptive mechanism responsible for supporting spatial memory consolidation in AD mice model.
DDRP: Real-time phenology and climatic suitability modeling of invasive insects
Authors: Barker Brittany S. , Coop Leonard , Wepprich Tyson , Grevstad Fritzi , Cook Gericke
Published: December 2020

Rapidly detecting and responding to new invasive species and the spread of those that are already established is essential for reducing their potential threat to food production, the economy, and the environment. We describe a new spatial modeling platform that integrates mapping of phenology and climatic suitability in real-time to provide timely and comprehensive guidance for stakeholders needing to know both where and when invasive insect species could potentially invade the conterminous United States. The Degree-Days, Risk, and Phenological event mapping (DDRP) platform serves as an open-source and relatively easy-to-parameterize decision support tool to help detect new invasive threats, schedule monitoring and management actions, optimize biological control, and predict potential impacts on agricultural production. DDRP uses a process-based modeling approach in which degree-days and temperature stress are calculated daily and accumulate over time to model phenology and climatic suitability, respectively. Outputs include predictions of the number of completed generations, life stages present, dates of phenological events, and climatically suitable areas based on two levels of climate stress. Species parameter values can be derived from laboratory and field studies or estimated through an additional modeling step. DDRP is written entirely in R, making it flexible and extensible, and capitalizes on multiple R packages to generate gridded and graphical outputs. We illustrate the DDRP modeling platform and the process of model parameterization using two invasive insect species as example threats to United States agriculture: the light brown apple moth,Epiphyas postvittana, and the small tomato borer,Neoleucinodes elegantalis. We then discuss example applications of DDRP as a decision support tool, review its potential limitations and sources of model error, and outline some ideas for future improvements to the platform.
Analysis of copy number variation in dogs implicates genomic structural variation in the development of anterior cruciate ligament rupture
Authors: Binversie Emily E. , Baker Lauren A. , Engelman Corinne D. , Hao Zhengling , Moran John J. , Piazza Alexander M. , Sample Susannah J. , Muir Peter
Published: December 2020

Anterior cruciate ligament (ACL) rupture is an important condition of the human knee. Second ruptures are common and societal costs are substantial. Canine cranial cruciate ligament (CCL) rupture closely models the human disease. CCL rupture is common in the Labrador Retriever (5.79% prevalence), ~100-fold more prevalent than in humans. Labrador Retriever CCL rupture is a polygenic complex disease, based on genome-wide association study (GWAS) of single nucleotide polymorphism (SNP) markers. Dissection of genetic variation in complex traits can be enhanced by studying structural variation, including copy number variants (CNVs). Dogs are an ideal model for CNV research because of reduced genetic variability within breeds and extensive phenotypic diversity across breeds. We studied the genetic etiology of CCL rupture by association analysis of CNV regions (CNVRs) using 110 case and 164 control Labrador Retrievers. CNVs were called from SNPs using three different programs (PennCNV, CNVPartition, and QuantiSNP). After quality control, CNV calls were combined to create CNVRs using ParseCNV and an association analysis was performed. We found no strong effect CNVRs but found 46 small effect (max(T) permutationP<0.05) CCL rupture associated CNVRs in 22 autosomes; 25 were deletions and 21 were duplications. Of the 46 CCL rupture associated CNVRs, we identified 39 unique regions. Thirty four were identified by a single calling algorithm, 3 were identified by two calling algorithms, and 2 were identified by all three algorithms. For 42 of the associated CNVRs, frequency in the population was <10% while 4 occurred at a frequency in the population ranging from 10–25%. Average CNVR length was 198,872bp and CNVRs covered 0.11 to 0.15% of the genome. All CNVRs were associated with case status. CNVRs did not overlap previous canine CCL rupture risk loci identified by GWAS. Associated CNVRs contained 152 annotated genes; 12 CNVRs did not have genes mapped to CanFam3.1. Using pathway analysis, a cluster of 19 homeobox domain transcript regulator genes was associated with CCL rupture (P= 6.6E-13). This gene cluster influences cranial-caudal body pattern formation during embryonic limb development. Clustered genes were found in 3 CNVRs on chromosome 14 (HoxA), 28 (NKX6-2), and 36 (HoxD). When analysis was limited to deletion CNVRs, the association was strengthened (P= 8.7E-16). This study suggests a component of the polygenic risk of CCL rupture in Labrador Retrievers is associated with small effect CNVs and may include aspects of stifle morphology regulated by homeobox domain transcript regulator genes.
Dietary factors associated with inflammatory laryngeal disease in South Korea
Authors: Jung Soo Yeon , Kim Min-ho , Lee So Jeong , Ha Eun Hee , Kim Han Su
Published: December 2020

Laryngeal inflammation causes not only benign diseases of the larynx, such as laryngitis and granuloma, but also malignancy. Dietary factors are known to control or modulate the inflammatory reaction in the body. To date, the association between laryngeal inflammation and dietary factors has not been reported using nationwide population-based data. The aim of this study was to analyze the association between several dietary factors and inflammatory laryngeal disease in the Korean population. This study analyzed the data from Korean National Health and Nutrition Examination Surveys which is cross-sectional nationwide-population-based study. Association between the dietary nutrient intake and the prevalence of inflammatory laryngeal diseases was analyzed in 21,116 participants who underwent a laryngoscopy and filled in the dietary intake questionnaires. Of the 21,116 participants included in the analysis, 758 (3.59%) were diagnosed with inflammatory laryngeal disease. Prevalence of inflammatory laryngeal disease was higher in men (4.58%) than in women (2.84%). The mean age of patients was 53.77 years. When analyzing the risk using propensity score matching, ILD group tend to consume more coffee and to intake less fiber and iron than normal group. On Logistic regression analysis, an increased intake of carbohydrate, fiber, and iron was associated with lowered risk of having ILD in female. The association between inflammatory laryngeal disease and dietary factors was prominent in the group aged ≥50 years and female. Increased intake of fiber, iron, and vitamin A were associated with lower risk in the group aged ≥50 years. In female, increased intake of fiber, iron were associated with lower risk of having ILD. In the group aged ≤50 years, only an increased consumption of makgeolli, Korean traditional rice wine, was associated with a higher risk of ILD.
Risk-benefit analysis of isoniazid monotherapy to prevent tuberculosis in patients with rheumatic diseases exposed to prolonged, high-dose glucocorticoids
Authors: Park Jun Won , Curtis Jeffrey R. , Lee Hajeong , Lee Jung-Kyu , Song Yeong Wook , Lee Eun Bong
Published: December 2020

Objective

To investigate the incidence of tuberculosis (TB) in patients with rheumatic diseases receiving high-dose glucocorticoids and to evaluate the preventive effect of isoniazid (INH).

Methods

This study included 1618 treatment episodes of prolonged (≥4 weeks), high-dose steroids (≥30mg/day of prednisone) in 1160 patients. Of these, INH was administered in 152 (9.4%) treatment episodes (INH group), while others received no prophylaxis (control group). The high-risk subgroup (n = 92) was defined as patients with 1) incomplete adherence to treatment of previous TB, 2) positive interferon-γ release assay, and/or 3) linear/reticular fibrotic lesions on chest radiographs. Primary outcome was 1-year incidence of TB in each group.

Results

During 1579.8 person-years, 21 cases of TB occurred. The high-risk subgroup showed a significantly higher TB incidence than the non-high-risk subgroup (Incidence rate ratio = 8.29). INH did not significantly affect the 1-year TB incidence in the whole population but numerically reduced it only in the high-risk subgroup [adjusted hazards ratio = 0.37 (95% CI, 0.002–5.10)]. The incidence of adverse drug reactions (ADRs) related to INH was 111.6 (89.3–137.9)/100 person-years, including one fatal occurrence of fulminant hepatitis. The number needed to treat (NNT) to prevent one case of TB was lower than the number needed to harm (NNH) for one case of severe ADR only in the high-risk subgroup (11 vs. 16).

Conclusion

INH treatment to prevent TB might be effective in high-risk patients but has a risk of frequent ADRs, which limits its use in general practice in patients not at a high risk of developing TB.
Hypoxia-inducible factor 1 alpha limits dendritic cell stimulation of CD8 T cell immunity
Authors: Tran Charles W. , Gold Matthew J. , Garcia-Batres Carlos , Tai Kelly , Elford Alisha R. , Himmel Megan E. , Elia Andrew J. , Ohashi Pamela S.
Published: December 2020

Dendritic cells are sentinels of the immune system and represent a key cell in the activation of the adaptive immune response. Hypoxia-inducible factor 1 alpha (HIF-1α)–a crucial oxygen sensor stabilized during hypoxic conditions–has been shown to have both activating and inhibitory effects in immune cells in a context- and cell-dependent manner. Previous studies have demonstrated that in some immune cell types, HIF-1α serves a pro-inflammatory role. Genetic deletion of HIF-1α in macrophages has been reported to reduce their pro-inflammatory function. In contrast, loss of HIF-1α enhanced the pro-inflammatory activity of dendritic cells in a bacterial infection model. In this study, we aimed to further clarify the effects of HIF-1α in dendritic cells. Constitutive expression of HIF-1α resulted in diminished immunostimulatory capacity of dendritic cells in vivo, while conditional deletion of HIF-1α in dendritic cells enhanced their ability to induce a cytotoxic T cell response. HIF-1α-expressing dendritic cells demonstrated increased production of inhibitory mediators including IL-10, iNOS and VEGF, which correlated with their reduced capacity to drive effector CD8+ T cell function. Altogether, these data reveal that HIF-1α can promote the anti-inflammatory functions of dendritic cells and provides insight into dysfunctional immune responses in the context of HIF-1α activation.
Emotion regulation of others’ positive and negative emotions is related to distinct patterns of heart rate variability and situational empathy
Authors: Jauniaux Josiane , Tessier Marie-Hélène , Regueiro Sophie , Chouchou Florian , Fortin-Côté Alexis , Jackson Philip L.
Published: December 2020

Although emotion regulation has been proposed to be crucial for empathy, investigations on emotion regulation have been primarily limited to intrapersonal processes, leaving the interpersonal processes of self-regulation rather unexplored. Moreover, studies showed that emotion regulation and empathy are related with increased autonomic activation. How emotion regulation and empathy are related at the autonomic level, and more specifically during differently valenced social situations remains an open question. Healthy adults viewed a series of short videos illustrating a target who was expressing positive, negative, or no emotions during a social situation (Positive, Negative, or Neutral Social Scenes). Prior to each video, participants were instructed to reappraise their own emotions (Up-regulation, Down-regulation, or No-regulation). To assess autonomic activation, RR intervals (RRI), high frequency (HF) components of heart rate variability (HRV), and electrodermal activity phasic responses (EDRs) were calculated. Situational empathy was measured through a visual analogue scale. Participants rated how empathic they felt for a specific target. Up- and Down-regulation were related to an increase and a decrease in situational empathy and an increase in RRI and HF, respectively, compared to the control condition (No-regulation). This suggests increased activity of the parasympathetic branch during emotion regulation of situational empathic responses. Positive compared to Negative Social Scenes were associated with decreased situational empathy, in addition to a slightly but non-significantly increased HF. Altogether, this study demonstrates that emotion regulation may be associated with changes in situational empathy and autonomic responses, preferentially dominated by the parasympathetic branch and possibly reflecting an increase of regulatory processes. Furthermore, the current study provides evidence that empathy for different emotional valences is associated with distinct changes in situational empathy and autonomic responses.
Associations of maternal diet quality with weight gain during pregnancy and obesity at three-year postpartum in Jakarta
Authors: Octavia Lestari , Agustina Rina , Sartika Arindah Nur , Utami Annisa Dwi , Dewi Yayang Aditia , Hayuningtyas Anastasia , Winanda Mutia , Prafiantini Erfi , Asmarinah
Published: December 2020

Dietary changes during pregnancy (DP) and post-partum are essential for women’s nutrition status and the health of their offspring. We compared the diet quality DP and at 3-year post-partum (3YPP) and assessed the relationship between maternal diet quality and nutritional status using a prospective cohort design among women in East Jakarta. In total, 107 women were recruited from the study in 2014 and followed up at 3YPP in 2018. The mid-upper arm circumference (MUAC), weight, and height were evaluated. Food consumption data were collected from repeated 24-h recalls. The validated US Diet Quality Index-Pregnancy (DQI-P) scores with eight components were calculated using the food consumption data and compared between DP and 3YPP. Associations of the DQI-P score with the MUAC and weight gain DP and body mass index (BMI) at 3YPP were analyzed using multivariable linear and logistic regression. The median of the DQI-P score DP was significantly higher than at 3YPP [35 (27; 42) versus 27 (19; 30); p-value <0.001, respectively]. The higher DQI-P score was associated with increased weight gain DP of 3.3 kg (adjusted β = 3.30, 95% confidence interval = 1.06–5.54) after adjusting for the mother's age and household income. The DQI-P score was not associated with an increased risk of chronic energy deficiency DP and overweight–obesity at 3YPP. Thus, the diet adequacy was associated with weight gain DP but did not affect the MUAC DP and BMI at 3YPP. The DQI-P score DP was slightly better than the diet at 3YPP; however, the overall diet quality was inadequate. In conclusion, a higher DQI-P score was associated with increased weight gain DP of 3.3 kg but was not associated with other nutritional status indices in DP and 3YPP. Innovative dietary quality improvement programs are required to reduce malnutrition risk in pregnant and reproductive-age women.
Limitations of rapid diagnostic tests in malaria surveys in areas with varied transmission intensity in Uganda 2017-2019: Implications for selection and use of HRP2 RDTs
Authors: Bosco Agaba B. , Nankabirwa Joaniter I. , Yeka Adoke , Nsobya Sam , Gresty Karryn , Anderson Karen , Mbaka Paul , Prosser Christiane , Smith David , Opigo Jimmy , Namubiru Rhoda , Arinaitwe Emmanuel , Kissa John , Gonahasa Samuel , Won Sungho , Lee Bora , Lim Chae Seung , Karamagi Charles , Cheng Qin , Nakayaga Joan K. , Kamya Moses R.
Published: December 2020

Background

Plasmodium falciparum histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDTs) are exclusively recommended for malaria diagnosis in Uganda; however, their functionality can be affected by parasite-related factors that have not been investigated in field settings.

Methods

Using a cross-sectional design, we analysed 219 RDT-/microscopy+ and 140 RDT+/microscopy+ dried blood spots obtained from symptomatic children aged 2–10 years from 48 districts in Uganda between 2017 and 2019. We aimed to investigate parasite-related factors contributing to false RDT results by molecular characterization of parasite isolates. ArcGIS software was used to map the geographical distribution of parasites. Statistical analysis was performed using chi-square or Fisher’s exact tests, with P ≤ 0.05 indicating significance. Odds ratios (ORs) were used to assess associations, while logistic regression was performed to explore possible factors associated with false RDT results.

Results

The presence of parasite DNA was confirmed in 92.5% (332/359) of the blood samples. The levels of agreement between the HRP2 RDT and PCR assay results in the (RDT+/microscopy+) and (RDT-/microscopy+) sample subsets were 97.8% (137/140) and 10.9% (24/219), respectively. Factors associated with false-negative RDT results in the (RDT-/microscopy+) samples were parasite density (<1,000/μl), pfhrp2/3 gene deletion and non-P. falciparum species (aOR 2.65, 95% CI: 1.62–4.38, P = 0.001; aOR 4.4, 95% CI 1.72–13.66, P = 0.004; and aOR 18.65, 95% CI: 5.3–38.7, P = 0.001, respectively). Overall, gene deletion and non-P. falciparum species contributed to 12.3% (24/195) and 19.0% (37/195) of false-negative RDT results, respectively. Of the false-negative RDTs results, 80.0% (156/195) were from subjects with low-density infections (< 25 parasites per 200 WBCs or <1,000/μl).

Conclusion

This is the first evaluation and report of the contributions of pfhrp2/3 gene deletion, non-P. falciparum species, and low-density infections to false-negative RDT results under field conditions in Uganda. In view of these findings, the use of HRP2 RDTs should be reconsidered; possibly, switching to combination RDTs that target alternative antigens, particularly in affected areas, may be beneficial. Future evaluations should consider larger and more representative surveys covering other regions of Uganda.
Comparative proteomics provides insights into diapause program of Bactrocera minax (Diptera: Tephritidae)
Authors: Wang Jia , Ran Li-Lin , Li Ying , Liu Ying-Hong
Published: December 2020

The Chinese citrus fly,Bactrocera minax, is a notorious univoltine pest that causes damage to citrus.B.minaxenters obligatory pupal diapause in each generation to resist harsh environmental conditions in winter. Despite the enormous efforts that have been made in the past decade, the understanding of pupal diapause ofB.minaxis currently still fragmentary. In this study, the 20-hydroxyecdysone solution and ethanol solvent was injected into newly-formed pupae to obtain non-diapause- (ND) and diapause-destined (D) pupae, respectively, and a comparative proteomics analysis between ND and D pupae was performed 1 and 15 d after injection. A total of 3,255 proteins were identified, of which 190 and 463 were found to be differentially abundant proteins (DAPs) in ND1vsD1 and ND15vsD15 comparisons, respectively. The reliability and accuracy of LFQ method was validated by qRT-PCR. Functional analyses of DAPs, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network construction, were conducted. The results revealed that the diapause program ofB.minaxis closely associated with several physiological activities, such as phosphorylation, chitin biosynthesis, autophagy, signaling pathways, endocytosis, skeletal muscle formation, protein metabolism, and core metabolic pathways of carbohydrate, amino acid, and lipid conversion. The findings of this study provide insights into diapause program ofB.minaxand lay a basis for further investigation into its underlying molecular mechanisms.
Analysis of interleukin-1 receptor associated kinase-3 (IRAK3) function in modulating expression of inflammatory markers in cell culture models: A systematic review and meta-analysis
Authors: Nguyen Trang Hong , Turek Ilona , Meehan-Andrews Terri , Zacharias Anita , Irving Helen
Published: December 2020

Background

IRAK3 is a critical modulator of inflammation in innate immunity. IRAK3 is associated with many inflammatory diseases, including sepsis, and is required in endotoxin tolerance to maintain homeostasis of inflammation. The impact of IRAK3 on inflammatory markers such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cell culture models remains controversial.

Objective

To analyse temporal effects of IRAK3 on inflammatory markers after one- or two-challenge interventions in cell culture models.

Methods

A systematic search was performed to identifyin vitrocell studies reporting outcome measures of expression of IRAK3 and inflammatory markers. Meta-analyses were performed where sufficient data were available. Comparisons of outcome measures were performed between different cell lines and human and mouse primary cells.

Results

The literature search identified 7766 studies for screening. After screening titles, abstracts and full-texts, a total of 89 studies were included in the systematic review.

Conclusions

The review identifies significant effects of IRAK3 on decreasing NF-κB DNA binding activity in cell lines, TNF-α protein level at intermediate time intervals (4h–15h) in cell lines or at long term intervals (16h–48h) in mouse primary cells following one-challenge. The patterns of TNF-α protein expression in human cell lines and human primary cells in response to one-challenge are more similar than in mouse primary cells. Meta-analyses confirm a negative correlation between IRAK3 and inflammatory cytokine (IL-6 and TNF-α) expression after two-challenges.
Interactomic affinity profiling by holdup assay: Acetylation and distal residues impact the PDZome-binding specificity of PTEN phosphatase
Authors: Jané Pau , Gógl Gergő , Kostmann Camille , Bich Goran , Girault Virginie , Caillet-Saguy Célia , Eberling Pascal , Vincentelli Renaud , Wolff Nicolas , Travé Gilles , Nominé Yves
Published: December 2020

Protein domains often recognize short linear protein motifs composed of a core conserved consensus sequence surrounded by less critical, modulatory positions. PTEN, a lipid phosphatase involved in phosphatidylinositol 3-kinase (PI3K) pathway, contains such a short motif located at the extreme C-terminus capable to recognize PDZ domains. It has been shown that the acetylation of this motif could modulate the interaction with several PDZ domains. Here we used an accurate experimental approach combining high-throughput holdup chromatographic assay and competitive fluorescence polarization technique to measure quantitative binding affinity profiles of the PDZ domain-binding motif (PBM) of PTEN. We substantially extended the previous knowledge towards the 266 known human PDZ domains, generating the full PDZome-binding profile of the PTEN PBM. We confirmed that inclusion of N-terminal flanking residues, acetylation or mutation of a lysine at a modulatory position significantly altered the PDZome-binding profile. A numerical specificity index is also introduced as an attempt to quantify the specificity of a given PBM over the complete PDZome. Our results highlight the impact of modulatory residues and post-translational modifications on PBM interactomes and their specificity.
Noise suppression ability and its mechanism analysis of scale-free spiking neural network under white Gaussian noise
Authors: Guo Lei , Kan Enyu , Wu Youxi , Lv Huan , Xu Guizhi
Published: December 2020

With the continuous improvement of automation and informatization, the electromagnetic environment has become increasingly complex. Traditional protection methods for electronic systems are facing with serious challenges. Biological nervous system has the self-adaptive advantages under the regulation of the nervous system. It is necessary to explore a new thought on electromagnetic protection by drawing from the self-adaptive advantage of the biological nervous system. In this study, the scale-free spiking neural network (SFSNN) is constructed, in which the Izhikevich neuron model is employed as a node, and the synaptic plasticity model including excitatory and inhibitory synapses is employed as an edge. Under white Gaussian noise, the noise suppression abilities of the SFSNNs with the high average clustering coefficient (ACC) and the SFSNNs with the low ACC are studied comparatively. The noise suppression mechanism of the SFSNN is explored. The experiment results demonstrate that the following. (1) The SFSNN has a certain degree of noise suppression ability, and the SFSNNs with the high ACC have higher noise suppression performance than the SFSNNs with the low ACC. (2) The neural information processing of the SFSNN is the linkage effect of dynamic changes in neuron firing, synaptic weight and topological characteristics. (3) The synaptic plasticity is the intrinsic factor of the noise suppression ability of the SFSNN.
Fish oil supplements, oxidative status, and compliance behaviour: Regulatory challenges and opportunities
Authors: Jairoun Ammar Abdulrahman , Shahwan Moyad , Zyoud Sa’ed H.
Published: December 2020

Background

Fish oil supplements that are rich in omega-3 long-chain polyunsaturated fatty acids (n-3 PUFAs). PUFAs are among the most widely-used dietary supplements globally, and millions of people consume them regularly. There have always been public concerns that these products should be guaranteed to be safe and of good quality, especially as these types of fish oil supplements are extremely susceptible to oxidative degradation.

Objectives

The aim of the current study is to investigate and examine the oxidation status of dietary supplements containing fish oils and to identify important factors related to the oxidation status of such supplements available in the United Arab Emirates (UAE).

Methods

A total of 44 fish oil supplements were analysed in this study. For each product, the oxidative parameters peroxide value (PV), anisidine value (AV), and total oxidation (TOTOX) were calculated, and comparisons were made with the guidelines supplied by the Global Organization for EPA and DHA Omega-3s (GOED). Median values for each of the above oxidative parameters were tested using the Kruskal-Wallis and Mann-Whitney U tests. P values < 0.05 were chosen as the statistically significant boundary.

Results

The estimate for the average PV value was 6.4 with a 95% confidence interval (CI) [4.2–8.7] compared to the maximum allowable limit of 5 meq/kg. The estimate for the average P-AV was 11 with a 95% CI [7.8–14.2] compared to the maximum allowable limit of 20. The estimate for the average TOTOX value was 23.8 meq/kg with a 95% CI [17.4–30.3] compared to the maximum allowable limit of 26 according to the GOED standards.

Conclusion

This research shows that most, although not all, of the fish oil supplements tested are compliant with the GOED oxidative quality standards. Nevertheless, it is clear that there should be a high level of inspection and control regarding authenticity, purity, quality, and safety in the processes of production and supply of dietary supplements containing fish oils.
The incidence of and risk factors for late presentation of childhood chronic kidney disease: A systematic review and meta-analysis
Authors: Plumb Lucy , Boother Emily J. , Caskey Fergus J. , Sinha Manish D. , Ben-Shlomo Yoav
Published: December 2020

Background

When detected early, inexpensive measures can slow chronic kidney disease progression to kidney failure which, for children, confers significant morbidity and impacts growth and development. Our objective was to determine the incidence of late presentation of childhood chronic kidney disease and its associated risk factors.

Methods

We searched MEDLINE, Embase, PubMed, Web of Science, Cochrane Library and CINAHL, grey literature and registry websites for observational data describing children <21 years presenting to nephrology services, with reference to late presentation (or synonyms thereof). Independent second review of eligibility, data extraction, and risk of bias was undertaken. Meta-analysis was used to generate pooled proportions for late presentation by definition and investigate risk factors. Meta-regression was undertaken to explore heterogeneity.

Results

Forty-five sources containing data from 30 countries were included, comprising 19,339 children. Most studies (37, n = 15,772) described children first presenting in kidney failure as a proportion of the chronic kidney disease population (mean proportion 0.43, 95% CI 0.34–0.54). Using this definition, the median incidence was 2.1 (IQR 0.9–3.9) per million age-related population. Risk associations included non-congenital disease and older age. Studies of hospitalised patients, or from low- or middle-income countries, that had older study populations than high-income countries, had higher proportions of late presentation.

Conclusions

Late presentation is a global problem among children with chronic kidney disease, with higher proportions seen in studies of hospitalised children or from low/middle-income countries. Children presenting late are older and more likely to have non-congenital kidney disease than timely presenting children. A consensus definition is important to further our understanding and local populations should identify modifiable barriers beyond age and disease to improve access to care.
Association between prediagnosis depression and mortality among postmenopausal women with colorectal cancer
Authors: Liang Xiaoyun , Hendryx Michael , Qi Lihong , Lane Dorothy , Luo Juhua
Published: December 2020

Background

There are no epidemiologic data on the relation of depression before colorectal cancer diagnosis to colorectal cancer mortality among women with colorectal cancer, especially those who are postmenopausal. Our aim was to fill this research gap.

Methods

We analyzed data from a large prospective cohort in the US, the Women’s Health Initiative (WHI). The study included 2,396 women with incident colorectal cancer, assessed for depressive symptoms and antidepressant use before cancer diagnosis at baseline (screening visit in the WHI study) during 1993–1998. Participants were followed up from cancer diagnosis till 2018. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) between depression (depressive symptoms or antidepressant use) at baseline, and all-cause mortality and colorectal cancer-specific mortality.

Results

Among women with colorectal cancer, there was no association between baseline depression and all-cause mortality or colorectal cancer-specific mortality after adjusting for age or multiple covariates.

Conclusion

Among women with colorectal cancer, there was no statistically significant association between depression before colorectal cancer diagnosis and all-cause mortality or colorectal cancer-specific mortality. Further studies are warranted to assess depressive symptoms and antidepressant use, measured at multiple points from baseline to diagnosis, and their interactions with specific types of colorectal cancer treatment on the risk of death from colorectal cancer.
Liver transplant waitlist removal, transplantation rates and post-transplant survival in Hispanics
Authors: Thuluvath Paul J. , Amjad Waseem , Zhang Talan
Published: December 2020

Background and objectives

Hispanics are the fastest growing population in the USA, and our objective was to determine their waitlist mortality rates, liver transplantation (LT) rates and post-LT outcomes.

Methods

All adults listed for LT with the UNOS from 2002 to 2018 were included. Competing risk analysis was performed to assess the association between ethnic group with waitlist removal due to death/deterioration and transplantation. For sensitivity analysis, Hispanics were matched 1:1 to Non-Hispanics using propensity scores, and outcomes of interest were compared in matched cohort.

Results

During this period, total of 154,818 patients who listed for liver transplant were involved in this study, of them 23,223 (15%) were Hispanics, 109,653 (71%) were Whites, 13,020 (8%) were Blacks, 6,980 (5%) were Asians and 1,942 (1%) were others. After adjusting for differences in clinical characteristics, compared to Whites, Hispanics had higher waitlist removal due to death or deterioration (adjusted cause-specific Hazard Ratio: 1.034, p = 0.01) and lower transplantation rates (adjusted cause-specific Hazard Ratio: 0.90, p<0.001). If Hispanics received liver transplant, they had better patient and graft survival than Non-Hispanics (p<0.001). Compared to Whites, adjusted hazard ratio for Hispanics were 0.88 (95% CI 0.84, 0.92, p<0.001) for patient survival and 0.90 (95% CI 0.86, 0.94, p<0.001) for graft survival. Our analysis in matched cohort showed the consistent results.

Conclusions

This study showed that Hispanics had higher probability to be removed from the waitlist due to death, and lower probability to be transplanted, however they had better post-LT outcomes when compared to whites.
Improved digital chest tomosynthesis image quality by use of a projection-based dual-energy virtual monochromatic convolutional neural network with super resolution
Authors: Gomi Tsutomu , Hara Hidetake , Watanabe Yusuke , Mizukami Shinya
Published: December 2020

We developed a novel dual-energy (DE) virtual monochromatic (VM) very-deep super-resolution (VDSR) method with an unsharp masking reconstruction algorithm (DE–VM–VDSR) that uses projection data to improve the nodule contrast and reduce ripple artifacts during chest digital tomosynthesis (DT). For estimating the residual errors from high-resolution and multiscale VM images from the projection space, the DE–VM–VDSR algorithm employs a training network (mini-batch stochastic gradient-descent algorithm with momentum) and a hybrid super-resolution (SR) image [simultaneous algebraic reconstruction technique (SART) total-variation (TV) first-iterative shrinkage–thresholding algorithm (FISTA); SART–TV–FISTA] that involves subjective reconstruction with bilateral filtering (BF) [DE–VM–VDSR with BF]. DE-DT imaging was accomplished by pulsed X-ray exposures rapidly switched between low (60 kV, 37 projection) and high (120 kV, 37 projection) tube-potential kVp by employing a 40° swing angle. This was followed by comparison of images obtained employing the conventional polychromatic filtered backprojection (FBP), SART, SART–TV–FISTA, and DE–VM–SART–TV–FISTA algorithms. The improvements in contrast, ripple artifacts, and resolution were compared using the signal-difference-to-noise ratio (SDNR), Gumbel distribution of the largest variations, radial modulation transfer function (radial MTF) for a chest phantom with simulated ground-glass opacity (GGO) nodules, and noise power spectrum (NPS) for uniform water phantom. The novel DE–VM–VDSR with BF improved the overall performance in terms of SDNR (DE–VM–VDSR with BF: 0.1603, without BF: 0.1517; FBP: 0.0521; SART: 0.0645; SART–TV–FISTA: 0.0984; and DE–VM–SART–TV–FISTA: 0.1004), obtained a Gumbel distribution that yielded good images showing the type of simulated GGO nodules used in the chest phantom, and reduced the ripple artifacts. The NPS of DE–VM–VDSR with BF showed the lowest noise characteristics in the high-frequency region (~0.8 cycles/mm). The DE–VM–VDSR without BF yielded an improved resolution relative to that of the conventional reconstruction algorithms for radial MTF analysis (0.2–0.3 cycles/mm). Finally, based on the overall image quality, DE–VM–VDSR with BF improved the contrast and reduced the high-frequency ripple artifacts and noise.
Assessing the effects of National Health Insurance reimbursement policy revisions for anti-osteoporotic drugs in Korean women aged 50 or older
Authors: Koo Ja Seo , Moon Seong Hwan , Lee Hankil , Park Sohee , Yu Yun Mi , Kang Hye-Young
Published: December 2020

Introduction

The Korean National Health Insurance revised its reimbursement criteria to expand coverage for anti-osteoporotic drug treatments in 2011 (expanding diagnostic criteria and the coverage period for anti-osteoporotic therapy) and 2015 (including osteoporotic fracture patients regardless of bone mineral density). We examined whether the two revisions contributed to an increase in the prescription rates of anti-osteoporotic drugs in Korea.

Methods

We used the Health Insurance Review and Assessment Service-National Patient Sample data from 2010 through 2016. A segmented regression analysis of interrupted time series was performed to assess changes in the monthly prescription rates of anti-osteoporotic drugs among women aged 50 or older, defined as the proportion of elderly women prescribed with anti-osteoporotic drugs.

Results

Both the levels (i.e., abrupt jump or drop) and the trends (i.e., slope) of the prescription rates of anti-osteoporotic drugs in the general population, osteoporotic patients, and osteoporotic fracture patients showed no significant changes after the first revision. However, there was a significant increase in the trends in the general population (β = 0.0166, p = 0.0173) and in osteoporotic patients (β = 0.1128, p = 0.0157) after the second revision. Women aged 65 to 79 years were the most significantly increased group in terms of the treatment proportion after the second revision because the trend was significant after the second revision in all three study populations (β = 0.0300, 0.1212, 0.1392, respectively; p < 0.05).

Conclusions

Although the two revisions expanded reimbursement coverage, only the second revision on reimbursing based on osteoporotic fracture regardless of bone mineral density was associated with increasing the proportion of post-menopausal women being treated with anti-osteoporotic drugs.
Do people have an ethical obligation to share their health information? Comparing narratives of altruism and health information sharing in a nationally representative sample
Authors: Raj Minakshi , De Vries Raymond , Nong Paige , Kardia Sharon L. R. , Platt Jodyn E.
Published: December 2020

Background

With the emergence of new health information technologies, health information can be shared across networks, with or without patients’ awareness and/or their consent. It is often argued that there can be an ethical obligation to participate in biomedical research, motivated by altruism, particularly when risks are low. In this study, we explore whether altruism contributes to the belief that there is an ethical obligation to share information about one’s health as well as how other health care experiences, perceptions, and concerns might be related to belief in such an obligation.

Methods

We conducted an online survey using the National Opinion Research Center’s (NORC) probability-based, nationally representative sample of U.S. adults. Our final analytic sample included complete responses from 2069 participants. We used multivariable logistic regression to examine how altruism, together with other knowledge, attitudes, and experiences contribute to the belief in an ethical obligation to allow health information to be used for research.

Results

We find in multivariable regression that general altruism is associated with a higher likelihood of belief in an ethical obligation to allow one’s health information to be used for research (OR = 1.22, SE = 0.14, p = 0.078). Trust in the health system and in care providers are both associated with a significantly higher likelihood of believing there is an ethical obligation to allow health information to be used (OR = 1.48, SE = 0.76, p<0.001; OR = 1.58, SE = 0.26, p<0.01, respectively).

Conclusions

Belief that there is an ethical obligation to allow one’s health information to be used for research is shaped by altruism and by one’s experience with, and perceptions of, health care and by general concerns about the use of personal information. Altruism cannot be assumed and researchers must recognize the ways encounters with the health care system influence (un)willingness to share one’s health information.
Intense light as anticoagulant therapy in humans
Authors: Oyama Yoshimasa , Shuff Sydney , Davizon-Castillo Pavel , Clendenen Nathan , Eckle Tobias
Published: December 2020

Blood coagulation is central to myocardial ischemia and reperfusion (IR) injury. Studies on the light elicited circadian rhythm protein Period 2 (PER2) using whole bodyPer2-/-mice found deficient platelet function and reduced clotting which would be expected to protect from myocardial IR-injury. In contrast, intense light induction of PER2 protected from myocardial IR-injury whilePer2deficiency was detrimental. Based on these conflicting data, we sought to evaluate the role of platelet specific PER2 in coagulation and myocardial ischemia and reperfusion injury. We demonstrated that platelets from mice with tissue-specific deletion ofPer2in the megakaryocyte lineage (Per2loxP/loxP-PF4-CRE) significantly clot faster than platelets from control mice. We further found increases in infarct sizes or plasma troponin levels inPer2loxP/loxP-PF4-CRE mice when compared to controls. As intense light increases PER2 protein in human tissues, we also performed translational studies and tested the effects of intense light therapy on coagulation in healthy human subjects. Our human studies revealed that intense light therapy repressed procoagulant pathways in human plasma samples and significantly reduced the clot rate. Based on these results we conclude that intense light elicited PER2 has an inhibitory function on platelet aggregation in mice. Further, we suggest intense light as a novel therapy to prevent or treat clotting in a clinical setting.