bluuebunny/crossref_metadata_2025 huggingface dataset:
At the Gate of Mutualism: Identification of Genomic Traits Predisposing to Insect-Bacterial Symbiosis in Pathogenic Strains of the Aphid Symbiont Serratia symbiotica
Authors: Renoz François , Foray Vincent , Ambroise Jérôme , Baa-Puyoulet Patrice , Bearzatto Bertrand , Mendez Gipsi Lima , Grigorescu Alina S. , Mahillon Jacques , Mardulyn Patrick , Gala Jean-Luc , Calevro Federica , Hance Thierry
Published: June 2021

Mutualistic associations between insects and heritable bacterial symbionts are ubiquitous in nature. The aphid symbiont Serratia symbiotica is a valuable candidate for studying the evolution of bacterial symbiosis in insects because it includes a wide diversity of strains that reflect the diverse relationships in which bacteria can be engaged with insects, from pathogenic interactions to obligate intracellular mutualism. The recent discovery of culturable strains, which are hypothesized to resemble the ancestors of intracellular strains, provide an opportunity to study the mechanisms underlying bacterial symbiosis in its early stages. In this study, we analyzed the genomes of three of these culturable strains that are pathogenic to aphid hosts, and performed comparative genomic analyses including mutualistic host-dependent strains. All three genomes are larger than those of the host-restricted S. symbiotica strains described so far, and show significant enrichment in pseudogenes and mobile elements, suggesting that these three pathogenic strains are in the early stages of the adaptation to their host. Compared to their intracellular mutualistic relatives, the three strains harbor a greater diversity of genes coding for virulence factors and metabolic pathways, suggesting that they are likely adapted to infect new hosts and are a potential source of metabolic innovation for insects. The presence in their genomes of secondary metabolism gene clusters associated with the production of antimicrobial compounds and phytotoxins supports the hypothesis that S. symbiotia symbionts evolved from plant-associated strains and that plants may serve as intermediate hosts. Mutualistic associations between insects and bacteria are the result of independent transitions to endosymbiosis initiated by the acquisition of environmental progenitors. In this context, the genomes of free-living S. symbiotica strains provide a rare opportunity to study the inventory of genes held by bacterial associates of insects that are at the gateway to a host-dependent lifestyle.
Hotter Drought Escalates Tree Cover Declines in Blue Oak Woodlands of California
Authors: Dwomoh Francis K. , Brown Jesslyn F. , Tollerud Heather J. , Auch Roger F.
Published: June 2021

California has, in recent years, become a hotspot of interannual climatic variability, recording devastating climate-related disturbances with severe effects on tree resources. Understanding the patterns of tree cover change associated with these events is vital for developing strategies to sustain critical habitats of endemic and threatened vegetation communities. We assessed patterns of tree cover change, especially the effects of the 2012–2016 drought within the distribution range of blue oak (Quercus douglasii), an endemic tree species to California with a narrow geographic extent. We utilized multiple, annual land-cover and land-surface change products from the U.S. Geological Survey (USGS) Land Change Monitoring, Assessment and Projection (LCMAP) project along with climate and wildfire datasets to monitor changes in tree cover state and condition and examine their relationships with interannual climate variability between 1985 and 2016. Here, we refer to a change in tree cover class without a land-cover change to another class as “conditional change.” The unusual drought of 2012–2016, accompanied by anomalously high temperatures and vapor pressure deficit, was associated with exceptional spikes in the amount of both fire and non-fire induced tree cover loss and tree cover conditional change, especially in 2015 and 2016. Approximately 1,266 km2 of tree cover loss and 617 km2 of tree cover conditional change were recorded during that drought. Tree cover loss through medium to high severity fires was especially large in exceptionally dry and hot years. Our study demonstrates the usefulness of the LCMAP products for monitoring the effects of climatic extremes and disturbance events on both thematic and conditional land-cover change over a multi-decadal period. Our results signify that blue oak woodlands may be vulnerable to extreme climate events and changing wildfire regimes. Here, we present early evidence that frequent droughts associated with climate warming may continue to affect tree cover in this region, while drought interaction with wildfires and the resulting feedbacks may have substantial influence as well. Consequently, efforts to conserve the blue oak woodlands, and potentially other vegetation communities in the Western United States, may benefit from consideration of climate risks as well as the potential for climate-fire and vegetation feedbacks.
A Longitudinal Analysis of Handwashing and Mask-Wearing During COVID-19
Authors: Croucher Stephen , Ashwell Douglas , Murray Niki , Condon Shawn Michael , Fletcher Phoebe
Published: June 2021

The COVID-19 pandemic has seen health preventive behaviors to prevent spread of the virus become highly politicized in the United States. A clear division exists between Democrats favoring health preventive measures and Republicans often defying such measures. Amid increasing fear of the virus, the 2020 United States presidential election became central to how the pandemic should be managed. This longitudinal study examines whether the frequency of handwashing and mask-wearing changed after the United States election. The study further explores whether political partisanship played a part in the change. Results show that handwashing and mask-wearing increased among Democrats after the election. However, Republican’s use of masks and handwashing decreased. These results are explained in terms of loyalty to outgoing President Trump among Republicans and renewed feelings of efficacy among Democrats.
Age Is a Predictor for the Syncope Recurrence in Elderly Vasovagal Syncope Patients With a Positive Head-Up Tilt Test
Authors: Guo Yongjuan , Chen Xiaomin , Zeng Tianze , Wang Lin , Cen Lvwei
Published: June 2021

Background: Valid predictors of the syncope recurrence in vasovagal syncope (VVS) patients with a positive head-up tilt test (HUTT) are currently lacking. The goal of this study was to identify the predictive performance of age for the recurrence of syncope in VVS patients with a positive HUTT.

Methods: In total, 175 VVS patients with a positive HUTT were observed for 6–32 months, and the recurrence of ≥1 syncope or typical pre-syncope prodromal episodes during follow-up was considered syncope recurrence. The population was divided into 2 groups, namely, a syncope recurrence group (44 patients) and a no syncope recurrence group (131 patients). The baseline clinical data, haemodynamic parameters, and classification of VVS on the HUTT were analyzed. Logistic regression was used to analyse the effect size and confidence interval for age. A receiver operating characteristic (ROC) curve analysis was used to assess the predictive performance and investigate the predictive value of age by the area under the curve (AUC).

Results: The median age of the syncope recurrence group was older than that of the no syncope recurrence group [60.0 (47.8, 66.0) years>53.0 (43.0, 62.0) years], and there was a significant difference between the two groups (P < 0.05). The trend for syncope recurrence changed with advancing age, and the logistic regression model adjusted by sex showed that older patients had an increased risk of syncope recurrence in VVS with a positive HUTT [OR value: 1.03, 95% confidence interval (CI): 1.008–1.061, p < 0.05]. Age was a valid predictor for the recurrence of syncope in elderly VVS patients with a positive HUTT (AUC: 0.688; 95% CI: 0.598–0.777, p < 0.05). The cut-off value was 53.5 years, and the sensitivity and specificity were 72.7 and 52.7%, respectively.

Conclusions: Age may be a valid predictor for syncope recurrence in elderly VVS patients with a positive HUTT. The rate of syncope recurrence increased with advancing age, especially in females.
Cost-Effectiveness Analysis of Direct Oral Anticoagulants Vs. Vitamin K Antagonists in the Elderly With Atrial Fibrillation: Insights From the Evidence in a Real-World Setting
Authors: Wu Yue , Zhang Chi , Gu Zhi-Chun
Published: June 2021

Background: In the clinical setting, the economic benefits of direct oral anticoagulants (DOACs) in elderly patients with atrial fibrillation (AF) remain unclear. This study aimed to estimate and compare the cost-effectiveness of DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) and vitamin K antagonists (VKAs; warfarin) in preventing stroke among AF patients aged >75 years in real-world practice.

Methods: A Markov model with a 10-year span was constructed to estimate the long-term clinical and economic outcomes among AF patients aged >75 years treated with DOACs and warfarin. The study was populated with a hypothetical cohort of 10,000 AF patients aged >75 years. Probabilities of clinical outcomes were obtained from the pooled observational studies (OSs), comparing DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) with VKAs. Other model inputs, including the utilities and the costs, were all estimated from public sources and the published literature. The costs, quality-adjusted life-years (QAYLs), and incremental cost-effectiveness ratios (ICER) were estimated for each treatment strategy. Subgroup analyses of individual DOACs and the scenario analysis were performed. Uncertainty was evaluated by deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA).

Results: Compared to warfarin, DOACs were associated with a gain of 0.36 QALY at an additional cost of $15,234.65, resulting in an ICER of $42,318.47 per QALY. Sensitivity analysis revealed that the ICER was sensitive to the cost of DOACs. Direct oral anticoagulants also shifted from dominating to dominated status When their annual costs of DOACs were over $3,802.84 or the risk ratio of death compared to warfarin was over 1.077%/year. Probabilistic sensitivity analysis (PSA) suggested that DOACs had a 53.83 and 90.7% probability of being cost-effective when the willingness-to-pay threshold was set at $50,000 and $100,000, respectively. Among all the four individual DOACs, edoxaban treatment was revealed as the preferred treatment strategy for the AF patients aged over 75 years by yielding the most significant health gain with the relatively low total cost.

Conclusions: Despite the high risk for major bleeding in elderly patients with AF, DOACs are more cost-effective treatment options than warfarin in real-world practice. Edoxaban was the preferred treatment strategy among four kinds of DOACs for AF patients aged over 75 years. Furthermore, beyond their safety profiles, the treatment benefits of DOACs assumed greater relevance and importance in older adults.
Estimation of the Pore Microstructure of Tight-Gas Sandstone Reservoirs with Seismic Data
Authors: Cheng Wei , Ba Jing , Carcione José M. , Pang Mengqiang , Wu Chunfang
Published: June 2021

Tight-sandstone reservoirs have a complex pore structure with microcracks and intergranular pores, which have a significant impact on the seismic properties. We have performed ultrasonic measurements at different confining pressures for 15 tight-gas sandstone samples of the Xujiahe formation in Western Sichuan Basin, and have available well-log and seismic data of this area. The aim of this work is to estimate the porosity and crack properties for variable pressure conditions. The EIAS (equivalent inclusion-average stress) model is adopted to compute the high- and low-frequency bulk and shear moduli as a function of crack aspect ratio and (soft) and (stiff) porosities. Then, we use the EIAS-Zener anelastic model to obtain the wave properties as a function of frequency, and compare results with those of the constant Q (Kjartansson) one for verification of the robustness of the approach. The corresponding P-wave impedance, density and phase velocity ratio (VP/VS) are computed in order to built 3D rock‐physics templates (RPTs) at the ultrasonic, well-log and seismic frequency bands. The methodology is applied to a survey line crossing two wells, which together with the laboratory experiments, provide calibration suitable data. The estimated stiff porosity and crack porosity and density are consistent with the available data and actual production records, indicating that 3D RPTs provide a useful interpretation tool in seismic exploration and prospect evaluation.
Synergistic Impact of Body Mass Index and Cognitive Function on All-Cause Mortality in Older Adults: A Nationwide Longitudinal Study
Authors: Han Ke , Jia Wangping , Wang Shengshu , Cao Wenzhe , Song Yang , Wang Jianwei , Liu Miao , Yang Shanshan , He Yao
Published: June 2021

Background

Body mass index (BMI) and cognitive function are independent predictors of mortality risk. However, little is known about the combined impact of BMI and cognitive function on the risk of all-cause mortality in older adults. In this study, we aimed to examine the associations between BMI, cognitive function, and all-cause mortality, including between-factor interactions, in the general population of older adults in China.

Methods

We used the data between 2011 and 2018 from the Chinese Longitudinal Healthy Longevity Survey that included adults aged ≥65 years residing in the 23 provinces of China. The association between BMI and cognitive function on all-cause mortality was examined with the Cox proportional hazards regression model.

Results

The study included 8,293 Chinese older adults. Low BMI (underweight) and cognitive impairment were associated with the highest risk of death after adjustments [hazard ratio (HR) = 2.18; 95% confidence interval (CI), 1.96–2.41]; this combined effect was more prominent among adults aged <100 years and women. In addition, there was an interaction effect of BMI and cognitive impairment on all-cause mortality (P <0.001). Concurrently, among older adults with normal cognition, the risk of mortality related to underweight was higher than among their cognitively impaired counterparts [55% (normal cognition) vs. 38% (cognitive impairment)].

Conclusions

Low BMI (underweight) and cognitive impairment were independently and jointly associated with increased risk of all-cause mortality among Chinese older adults, and females showed a stronger effect in this association. The association between BMI and mortality was more pronounced in the participants with normal cognition than in their cognitively impaired counterparts.
Clinical Perspectives on the Use of Subcutaneous and Oral Formulations of Semaglutide
Authors: Gallwitz Baptist , Giorgino Francesco
Published: June 2021

Early and effective glycemic control can prevent or delay the complications associated with type 2 diabetes (T2D). The benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming increasingly recognized and they now feature prominently in international T2D treatment recommendations and guidelines across the disease continuum. However, despite providing effective glycemic control, weight loss, and a low risk of hypoglycemia, GLP-1RAs are currently underutilized in clinical practice. The long-acting GLP-1RA, semaglutide, is available for once-weekly injection and in a new once-daily oral formulation. Semaglutide is an advantageous choice for the treatment of T2D since it has greater efficacy in reducing glycated hemoglobin and body weight compared with other GLP-1RAs, has demonstrated benefits in reducing major adverse cardiovascular events, and has a favorable profile in special populations (e.g., patients with hepatic impairment or renal impairment). The oral formulation represents a useful option to help improve acceptance and adherence compared with injectable formulations for patients with a preference for oral therapy, and may lead to earlier and broader use of GLP-1RAs in the T2D treatment trajectory. Oral semaglutide should be taken on an empty stomach, which may influence the choice of formulation. As with most GLP-1RAs, initial dose escalation of semaglutide is required for both formulations to mitigate gastrointestinal adverse events. There are also specific dose instructions to follow with oral semaglutide to ensure sufficient gastric absorption. The evidence base surrounding the clinical use of semaglutide is being further expanded with trials investigating effects on diabetic retinopathy, cardiovascular outcomes, and on the common T2D comorbidities of obesity, chronic kidney disease, and non-alcoholic steatohepatitis. These will provide further information about whether the benefits of semaglutide extend to these other indications.
Maternal GALNT2 Variations Affect Blood Pressure, Atherogenic Index, and Fetal Growth, Depending on BMI in Gestational Diabetes Mellitus
Authors: Guan Linbo , Fan Ping , Liu Xinghui , Zhou Mi , Wu Yujie , Liu Rui , Liu Yu , Bai Huai
Published: June 2021

Background

GALNT2 is a GalNAc transferase that regulates serum lipid fractions, insulin signaling, and lipogenesis. Genetic variants are implicated in the pathogenesis of gestational diabetes mellitus (GDM). The objective of this study was to investigate the association of GALNT2 rs2144300 and rs4846914 single nucleotide polymorphisms (SNPs) with the risk of GDM and related traits.

Methods

Two SNPs were genotyped, and clinical and metabolic parameters were determined in 461 GDM patients and 626 control subjects. Genetic associations with related traits were also analyzed.

Results

The genotype distributions of the two SNPs in GDM patients were similar to those in normal controls. However, significant differences were noted across the three groups of genotypes with respect to the examined variables in subjects in a BMI-dependent manner. The rs4846914 and rs2144300 SNPs of GALNT2 were significantly associated with systolic blood pressure and/or diastolic blood pressure levels in nonobese GDM patients and atherogenic index (AI) in overweight/obese GDM patients. The rs4846914 SNP was also associated with fetal growth in overweight/obese GDM patients, and apo A1 and pregnancy weight gain in overweight/obese control women (all P<0.05).

Conclusions

The two polymorphisms in the GALNT2 gene are associated with variations in blood pressure, atherogenic index, and fetal growth in GDM, depending on BMI, but not with GDM. Our findings highlight a link between related phenotypes in GDM mothers and their fetuses and the genetic components.
An Eulerian Single-Phase Transport Model for Solid Fission Products in the Molten Salt Fast Reactor: Development of an Analytical Solution for Verification Purposes
Authors: Di Ronco Andrea , Lorenzi Stefano , Giacobbo Francesca , Cammi Antonio
Published: June 2021

Nuclear reactor modeling has been shifting, over the last decades, towards full-core multiphysics analysis due to the ever-increasing safety requirements and complexity of the designs of innovative systems. This is particularly true for liquid-fuel reactor concepts such as the Molten Salt Fast Reactor (MSFR), given their strong intrinsic coupling between thermal-hydraulics, neutronics and fuel chemistry. In the MSFR, fission products (FPs) are originated within the liquid fuel and are carried by the fuel flow all over the reactor core and through pumping and heat exchange systems. Some of FP species, in the form of solid precipitates, can represent a major design and safety challenge, e.g., due to deposition on solid boundaries, and their distribution in the core is relevant to the design and safety analysis of the reactor. In this regard it is essential, both for the design and the safety assessment of the reactor, the capability to model the transport of solid FPs and their deposition to the boundary (e.g., wall or heat exchanger structures). To this aim, in this study, models of transport of solid FPs in the MSFR are developed and verified. An Eulerian single-phase transport model is developed and integrated in a consolidated multiphysics model of the MSFR based on the open-source CFD library OpenFOAM. In particular, general mixed-type deposition boundary conditions are considered, to possibly describe different kinds of particle-wall interaction mechanisms. For verification purposes, analytical solutions for simple case studies are derived ad hoc based on the extension of the classic Graetz problem to linear decay, distributed source terms and mixed-type boundary conditions. The results show excellent agreement between the two models, and highlight the effects of decay and deposition phenomena of various intensity. The resulting approach constitutes a computationally efficient tool to extend the capabilities of CFD-based multiphysics MSFR calculations towards the simulation of solid fission products transport.
Seasonal Patterns of Fat Deposits in Relation to Migratory Strategy in Facultative Migrants
Authors: Cornelius Jamie M. , Hahn Thomas P. , Robart Ashley R. , Vernasco Ben J. , Zahor Dorothy L. , Glynn Kenneth J. , Navis Corrie J. , Watts Heather E.
Published: June 2021

Physiological preparations for migration generally reflect migratory strategy. Migrant birds fuel long-distance flight primarily with lipids, but carrying excess fuel is costly; thus, the amount of fat deposited prior to departure often reflects the anticipated flight duration or distance between refueling bouts. Seasonal pre-migratory deposition of fat is well documented in regular seasonal migrants, but is less described for more facultative species. We analyze fat deposits of free-living birds across several taxa of facultative migrants in the songbird subfamily Carduelinae, including house finches (Haemorhous mexicanus), American goldfinches (Spinus tristis), pine siskins (Spinus pinus) and four different North American ecotypes of red crossbills (Loxia curvirostra), to evaluate seasonal fat deposition during facultative migratory periods. Our data suggest that the extent of seasonal fat deposits corresponds with migratory tendency in these facultative taxa. Specifically, nomadic red crossbills with a seasonally predictable annual movement demonstrated relatively large seasonal fat deposits coincident with the migratory periods. In contrast, pine siskins, thought to be more variable in timing and initiation of nomadic movements, had smaller peaks in fat deposits during the migratory season, and the partial migrant American goldfinch and the resident house finch showed no peaks coincident with migratory periods. Within the red crossbills, those ecotypes that are closely associated with pine habitats showed larger peaks in fat deposits coincident with autumn migratory periods and had higher wing loading, whereas those ecotypes associated with spruces, Douglas-fir and hemlocks showed larger peaks coincident with spring migratory periods and lower wing loading. We conclude that population averages of fat deposits do reflect facultative migration strategies in these species, as well as the winter thermogenic challenges at the study locations. A difference in seasonal fattening and wing loading among red crossbill ecotypes is consistent with the possibility that they differ in their migratory biology, and we discuss these differences in light of crossbill reproductive schedules and phenologies of different conifer species.
Improved Understanding of the Role of Gene and Genome Duplications in Chordate Evolution With New Genome and Transcriptome Sequences
Authors: Aase-Remedios Madeleine E. , Ferrier David E. K.
Published: June 2021

Comparative approaches to understanding chordate genomes have uncovered a significant role for gene duplications, including whole genome duplications (WGDs), giving rise to and expanding gene families. In developmental biology, gene families created and expanded by both tandem and WGDs are paramount. These genes, often involved in transcription and signalling, are candidates for underpinning major evolutionary transitions because they are particularly prone to retention and subfunctionalisation, neofunctionalisation, or specialisation following duplication. Under the subfunctionalisation model, duplication lays the foundation for the diversification of paralogues, especially in the context of gene regulation. Tandemly duplicated paralogues reside in the same regulatory environment, which may constrain them and result in a gene cluster with closely linked but subtly different expression patterns and functions. Ohnologues (WGD paralogues) often diversify by partitioning their expression domains between retained paralogues, amidst the many changes in the genome during rediploidisation, including chromosomal rearrangements and extensive gene losses. The patterns of these retentions and losses are still not fully understood, nor is the full extent of the impact of gene duplication on chordate evolution. The growing number of sequencing projects, genomic resources, transcriptomics, and improvements to genome assemblies for diverse chordates from non-model and under-sampled lineages like the coelacanth, as well as key lineages, such as amphioxus and lamprey, has allowed more informative comparisons within developmental gene families as well as revealing the extent of conserved synteny across whole genomes. This influx of data provides the tools necessary for phylogenetically informed comparative genomics, which will bring us closer to understanding the evolution of chordate body plan diversity and the changes underpinning the origin and diversification of vertebrates.
Molecular and Clinical Characterization of LAG3 in Breast Cancer Through 2994 Samples
Authors: Liu Qiang , Qi Yihang , Zhai Jie , Kong Xiangyi , Wang Xiangyu , Wang Zhongzhao , Fang Yi , Wang Jing
Published: June 2021

Despite the promising impact of cancer immunotherapy targeting CTLA4 and PD1/PDL1, numerous cancer patients fail to respond. LAG3 (Lymphocyte Activating 3), also named CD233, serves as an alternative inhibitory receptor to be targeted in the clinic. The impacts of LAG3 on immune cell populations and coregulation of immune responses in breast cancer remain largely unknown. To characterize the role of LAG3 in breast cancer, we investigated transcriptome data and associated clinical information derived from 2,994 breast cancer patients. We estimated the landscape of the relationship between LAG3 and 10 types of cell populations of breast cancer. We investigated the correlation pattern between LAG3 and immune modulators in pancancer, particularly the synergistic role of LAG3 with other immune checkpoint members in breast cancer. LAG3 expression was closely related to the malignancy of breast cancer and may serve as a potential biomarker. LAG3 may play an important role in regulating the tumor immune microenvironment of T cells and other immune cells. More important, LAG3 may synergize with CTLA4, PD1/PDL1, and other immune checkpoints, thereby contributing more evidence to improve combination cancer immunotherapy by simultaneously targeting LAG3, PD1/PDL1, and CTLA4.
Influence of Seasonal Vitamin D Changes on Clinical Manifestations of Rheumatoid Arthritis and Systemic Sclerosis
Authors: Cutolo Maurizio , Soldano Stefano , Sulli Alberto , Smith Vanessa , Gotelli Emanuele
Published: June 2021

Vitamin D [1,25(OH)2D—calcitriol] is basically a steroid hormone with pleiotropic biologic effects, and its impact on the regulation of immune system may influence several clinical conditions. Calcidiol (25OHD), as precursor of calcitriol, derives, for the most part (80%), from cutaneous cholesterol (7-dehydrocholesterol) under the action of UV-B (sunlight). Consequently, serum concentrations fluctuate during the year following the circannual rhythm of sun exposition. We will update about the available evidence regarding the complex influence of seasonal vitamin D changes on two different chronic connective tissue diseases, namely rheumatoid arthritis (RA) and systemic sclerosis (SSc). Notably, RA is an emblematic model of autoimmune disease with prevalent joint inflammatory features, while SSc is mainly an autoimmune progressive pro-fibrotic disease. However, in both conditions, low serum concentrations of 25OHD are involved in the pathogenesis of the diseases, and emerging data report their impact on clinical manifestations.
Manganese Benefits Heat-Stressed Corals at the Cellular Level
Authors: Montalbetti Enrico , Biscéré Tom , Ferrier-Pagès Christine , Houlbrèque Fanny , Orlandi Ivan , Forcella Matilde , Galli Paolo , Vai Marina , Seveso Davide
Published: June 2021

The intensity and frequency of coral bleaching events have increased worldwide especially due to thermal stress and seawater pollution. Although it has been observed that metal concentration in seawater can affect the coral’s ability to adopt cellular defensive mechanisms to counteract bleaching, more investigations are needed to better understand the role of metals in coral physiology. In this study, we analyzed the individual and combined effects of prolonged heat stress and manganese (Mn) and iron (Fe) enrichments at the cellular level on the coralStylophora pistillata. Thermal stress caused an up-regulation in the expression of the host Heat shock proteins (Hsps) 60 and 70, which showed a parallel pattern of modulation in all treatments, as well as an increase of lipid peroxidation (LPO) in the holobiont. Fe enrichment did not induce any change in Hsp expression or in the oxidative status of the corals both at the ambient temperature of 26°C or at increased temperature, suggesting that Fe didn’t seem to play a role in mitigating the cellular damages and the coral bleaching. Mn or MnFe enrichment at 26°C seemed to increase the oxidative stress in zooxanthellae, since high LPO and glutathione reductase (GR) levels were recorded, but it did not cause any effect on polyp Hsp expression, probably due to the antioxidant action of GR. With the temperature increase, Mn enrichments prevented any increase in Hsp levels and caused a significant decrease of LPO and GR activity, strengthening a previous hypothesis suggesting that Mn could mitigate the negative cellular effects produced by the thermal stress.
Marine Heatwaves Exceed Cardiac Thermal Limits of Adult Sparid Fish (Diplodus capensis, Smith 1884)
Authors: van der Walt Kerry-Ann , Potts Warren M. , Porri Francesca , Winkler Alexander C. , Duncan Murray I. , Skeeles Michael R. , James Nicola C.
Published: June 2021

Climate change not only drives increases in global mean ocean temperatures, but also in the intensity and duration of marine heatwaves (MHWs), with potentially deleterious effects on local fishes. A first step to assess the vulnerability of fishes to MHWs is to quantify their upper thermal thresholds and contrast these limits against current and future ocean temperatures during such heating events. Heart failure is considered a primary mechanism governing the upper thermal limits of fishes and begins to occur at temperatures where heart rate fails to keep pace with thermal dependency of reaction rates. This point is identified by estimating the Arrhenius breakpoint temperature (TAB), which is the temperature where maximum heart rate (fHmax) first deviates from its exponential increase with temperature and the incremental Q10 breakpoint temperature (TQB), which is where the Q10 temperature coefficient (relative change in heart rate for a 10°C increase in temperature) for fHmax abruptly decreases during acute warming. Here we determined TAB, TQB and the temperature that causes cardiac arrhythmia (TARR) in adults of the marine sparid, Diplodus capensis, using an established technique. Using these thermal indices results, we further estimated adult D. capensis vulnerability to contemporary MHWs and increases in ocean temperatures along the warm-temperate south-east coast of South Africa. For the established technique, we stimulated fHmax with atropine and isoproterenol and used internal heart rate loggers to measure fHmax under conditions of acute warming in the laboratory. We estimated average TAB, TQB, and TARR values of 20.8°C, 21.0°C, and 28.3°C. These findings indicate that the physiology of D. capensis will be progressively compromised when temperatures exceed 21.0°C up to a thermal end-point of 28.3°C. Recent MHWs along the warm-temperate south-east coast, furthermore, are already occurring within the TARR threshold (26.6–30.0°C) for cardiac function in adult D. capensis, suggesting that this species may already be physiologically compromised by MHWs. Predicted increases in mean ocean temperatures of a conservative 2.0°C, may further result in adult D. capensis experiencing more frequent MHWs as well as a contraction of the northern range limit of this species as mean summer temperatures exceed the average TARR of 28.3°C.
Chronic Prurigo: Similar Clinical Profile and Burden Across Clinical Phenotypes
Authors: Zeidler Claudia , Pereira Manuel Pedro , Ständer Sonja
Published: June 2021

Chronic prurigo is a debilitating skin disease characterized by the presence of chronic pruritus and scratching-related pruriginous lesions. The pruriginous lesions can differ in their clinics what has recently been categorized into different clinical phenotypes. The most common one is chronic nodular prurigo (syn. prurigo nodularis); other phenotypes are papular, plaque, umbilicated, and linear prurigo. A comparison between these phenotypes regarding similarities and differences has not yet been performed. In this explorative analysis, itch characteristics, scratching behavior, and disease burden of the nodular, papular, plaque, and umbilicated prurigo were investigated in 1,128 patients. Patients with nodular and plaque prurigo were younger than patients with papular and umbilicated prurigo. The shortest duration of the underlying pruritus was found in papular and umbilicated prurigo, the longest in plaque prurigo. Itch intensity, impairment of sleep, mood and the quality of life did not differ. These findings confirm that the clinical phenotypes of chronic prurigo belong to a spectrum of one disease with similar disease characteristics and can be categorized under the umbrella term of chronic prurigo. Future clinical trials should include all phenotypes of chronic prurigo.
Reaching Absent and Refusing Individuals During Home-Based HIV Testing Through Self-Testing—at What Cost?
Authors: Amstutz Alain , Matsela Lineo , Lejone Thabo Ishmael , Kopo Mathebe , Glass Tracy Renée , Labhardt Niklaus Daniel
Published: June 2021

Introduction: In the HOSENG trial (NCT03598686), the secondary distribution of oral self-tests for persons absent or refusing to test during a home-based HIV testing campaign in rural Lesotho resulted in an increase in testing coverage of 21% compared to a testing campaign without secondary distribution. This study aims to determine the per patient costs of both HOSENG trial arms.

Method: We conducted a micro-costing study to estimate the cost of home-based HIV testing with (HOSENG intervention arm) and without (HOSENG control arm) secondary self-test distribution from a provider's perspective. A mixture of top-down and bottom-up costing was used. We estimated both the financial and economic per patient costs of each possible testing cascade scenario. The costs were adjusted to 2018 US$.

Results: The overall provider cost for delivering the home-based HIV testing with secondary distribution was US$36,481 among the 4,174 persons enumerated and 3,094 eligible for testing in the intervention villages compared to US$28,620 for 3,642 persons enumerated and 2,727 eligible for testing in the control. The cost per person eligible for testing was US$11.79 in the intervention vs. US$10.50 in the control. This difference was mainly driven by the cost of distributed oral self-tests. The cost per person tested was, however, lower in intervention villages (US$15.70 vs. US$22.15) due to the higher testing coverage achieved through self-test distribution. The cost per person confirmed new HIV+ was US$889.79 in the intervention and US$753.17 in the control.

Conclusion: During home-based HIV testing in Lesotho, the secondary distribution of self-tests for persons absent or refusing to test during the visit reduced the costs per person tested and thus presents a promising add-on for such campaigns.

Trial Registration:https://ClinicalTrials.gov/, identifier: NCT03598686
Identifying Sources of Faecal Contamination in a Small Urban Stream Catchment: A Multiparametric Approach
Authors: Reynolds Liam J. , Martin Niamh A. , Sala-Comorera Laura , Callanan Kevin , Doyle Padraig , O’Leary Clare , Buggy Paul , Nolan Tristan M. , O’Hare Gregory M. P. , O’Sullivan John J. , Meijer Wim G.
Published: June 2021

Small urban streams discharging in the proximity of bathing waters may significantly contribute to the deterioration of water quality, yet their impact may be overlooked. This study focuses on the Elm Park stream in the city of Dublin that is subject to faecal contamination by unidentified sources. The aim of the study was to identify a minimum number of “sentinel” sampling stations in an urban catchment that would provide the maximum amount of information regarding faecal pollution in the catchment. Thus, high-resolution sampling within the catchment was carried out over the course of 1 year at 11 stations. Faecal indicator bacteria were enumerated and microbial source tracking (MST) was employed to evaluate human pollution. In addition, ammonium, total oxidised nitrogen, and phosphorus levels were monitored to determine if these correlated with faecal indicator and the HF183 MST marker. In addition, the effect of severe weather events on water quality was assessed using automated sampling at one of the identified “sentinel” stations during baseflow and high flow conditions over a 24-h period. Our results show that this urban stream is at times highly contaminated by point source faecal pollution and that human faecal pollution is pervasive in the catchment. Correlations between ammonium concentrations and faecal indicator bacteria (FIB) as well as the human MST marker were observed during the study. Cluster analysis identified four “sentinel” stations that provide sufficient information on faecal pollution in the stream, thus reducing the geographical complexity of the catchment. Furthermore, ammonium levels strongly correlated with FIB and the human HF183 MST marker under high flow conditions at key “sentinel” stations. This work demonstrates the effectiveness of pairing MST, faecal indicators, and ammonium monitoring to identify “sentinel” stations that could be more rapidly assessed using real-time ammonium readouts to assess remediation efforts.
Assessing Biosynthetic Gene Cluster Diversity of Specialized Metabolites in the Conserved Gut Symbionts of Herbivorous Turtle Ants
Authors: Chanson Anaïs , Moreau Corrie S. , Duplais Christophe
Published: June 2021

Cephalotes are herbivorous ants (>115 species) feeding on low-nitrogen food sources, and they rely on gut symbionts to supplement their diet by recycling nitrogen food waste into amino acids. These conserved gut symbionts, which encompass five bacterial orders, have been studied previously for their primary nitrogen metabolism; however, little is known about their ability to biosynthesize specialized metabolites which can play a role in bacterial interactions between communities living in close proximity in the gut. To evaluate the biosynthetic potential of their gut symbionts, we mine 14 cultured isolate genomes and gut metagenomes across 17 Cephalotes species to explore the biodiversity of biosynthetic gene clusters (BGCs) producing specialized metabolites. The diversity of BGCs across Cephalotes phylogeny was analyzed using sequence similarity networking and BGC phylogenetic reconstruction. Our results reveal that the conserved gut symbionts involved in the nutritional symbiosis possess 80% of all the 233 BGCs retrieved in this work. Furthermore, the phylogenetic analysis of BGCs reveals different patterns of distribution, suggesting different mechanisms of conservation. A siderophore BGC shows high similarity in a single symbiont across different ant host species, whereas a BGC encoding the production of non-ribosomal peptides (NRPs) found different symbionts within a single host species. Additionally, BGCs were abundant in four of the five bacterial orders of conserved symbionts co-occurring in the hindgut. However, one major symbiont localized alone in the midgut lack BGCs. Because the spatial isolation prevents direct interaction with other symbionts, this result supports the idea that BGCs are maintained in bacteria living in close proximity but are dispensable for an alone-living symbiont. These findings together pave the way for studying the mechanisms of BGC conservation and evolution in gut bacterial genomes associated with Cephalotes. This work also provides a genetic background for further study, aiming to characterize bacterial specialized metabolites and to understand their functional role in multipartite mutualisms between conserved gut symbionts and Cephalotes turtle ants.
Molecular Characteristics of Human Adenovirus Type 3 Circulating in Parts of China During 2014–2018
Authors: Duan Yali , Xu Baoping , Li Changchong , Bao Yixiao , An Shuhua , Zhou Yunlian , Chen Aihuan , Deng Li , Ning Limin , Zhu Yun , Wang Wei , Zhang Meng , Xu Lili , Chen Xiangpeng , Xie Zhengde
Published: June 2021

Human adenoviruses (HAdVs) are important pathogens causing respiratory infections; 3.5–11% of childhood community-acquired pneumonia is associated with HAdV infection. Human adenovirus type 3 (HAdV-3), leading to severe morbidity and mortality, is one of the most prevalent genotype among adenoviruses responsible for acute respiratory infections (ARIs) in children in China. To identify the genetic variation of HAdV-3 in children with ARIs in China, a molecular epidemiological study was conducted. A total of 54 HAdV-3 isolated strains were obtained from children with ARIs in Beijing, Wenzhou, Shanghai, Shijiazhuang, Hangzhou, Guangzhou, and Changchun from 2014 to 2018. Thirty-two strains of which were selected for whole-genome sequencing, while the hexon, penton base, and fiber genes were sequenced for remaining strains. Bioinformatics analysis was performed on the obtained sequences. The phylogenetic analyses based on whole-genome sequences, major capsid protein genes (hexon, penton base, and fiber), and early genes (E1, E2, E3, and E4) showed that the HAdV-3 strains obtained in this study always clustered together with the reference strains from Chinese mainland, while the HAdV-3 prototype strain formed a cluster independently. Compared with the prototype strain, all strains possessed nine amino acid (AA) substitutions at neutralization antigenic epitopes of hexon. The homology models of the hexon protein of the HAdV-3 prototype and strain BJ20160214 showed that there was no evident structural change at the AA mutation sites. Two AA substitutions were found at the Arg-Gly-Asp (RGD) loop and hypervariable region 1 (HVR1) region of the penton base. A distinct AA insertion (20P) in the highly conserved PPPSY motif of the penton base that had never been reported before was observed. Recombination analysis indicated that partial regions of protein IIIa precursor, penton base, and protein VII precursor genes among all HAdV-3 strains in this study were from HAdV-7. This study showed that the genomes of the HAdV-3 strains in China were highly homologous. Some AA mutations were found at antigenic sites; however, the significance needs further study. Our data demonstrated the molecular characteristics of HAdV-3 circulating in China and was highly beneficial for further epidemiological exploration and the development of vaccines and drugs against HAdV-3.
Regulation of ADAMTS Proteases
Authors: Rose Keron W. J. , Taye Nandaraj , Karoulias Stylianos Z. , Hubmacher Dirk
Published: June 2021

A disintegrin and metalloprotease with thrombospondin type I motifs (ADAMTS) proteases are secreted metalloproteinases that play key roles in the formation, homeostasis and remodeling of the extracellular matrix (ECM). The substrate spectrum of ADAMTS proteases can range from individual ECM proteins to entire families of ECM proteins, such as the hyalectans. ADAMTS-mediated substrate cleavage is required for the formation, remodeling and physiological adaptation of the ECM to the needs of individual tissues and organ systems. However, ADAMTS proteases can also be involved in the destruction of tissues, resulting in pathologies such as arthritis. Specifically, ADAMTS4 and ADAMTS5 contribute to irreparable cartilage erosion by degrading aggrecan, which is a major constituent of cartilage. Arthritic joint damage is a major contributor to musculoskeletal morbidity and the most frequent clinical indication for total joint arthroplasty. Due to the high sequence homology of ADAMTS proteases in their catalytically active site, it remains a formidable challenge to design ADAMTS isotype-specific inhibitors that selectively inhibit ADAMTS proteases responsible for tissue destruction without affecting the beneficial functions of other ADAMTS proteases. In vivo, proteolytic activity of ADAMTS proteases is regulated on the transcriptional and posttranslational level. Here, we review the current knowledge of mechanisms that regulate ADAMTS protease activity in tissues including factors that induce ADAMTS gene expression, consequences of posttranslational modifications such as furin processing, the role of endogenous inhibitors and pharmacological approaches to limit ADAMTS protease activity in tissues, which almost exclusively focus on inhibiting the aggrecanase activity of ADAMTS4 and ADAMTS5.
A Systematic Review and Meta-Analysis of Retinal Microvascular Features in Alzheimer's Disease
Authors: Jin Qifang , Lei Yiming , Wang Ruoxin , Wu Huiying , Ji Kaibao , Ling Ling
Published: June 2021

Objective: The aim of this meta-analysis was to investigate retinal microvascular features in patients with Alzheimer's disease (AD) using optical coherence tomography angiography (OCTA).

Methods: PubMed, Cochrane Library, Embase, and Web of Science databases were systematically searched for published articles comparing retinal microvascular characteristics in subjects with AD and controls. The mean difference (MD) with a 95% confidence interval (CI) was used to assess continuous variables. Review Manager Version (RevMan) 5.30, was employed to analyze the data.

Results: Nine studies were included in the meta-analysis. The analysis revealed that the macular whole enface superficial and deep vessel density (VD) values measured by OCTA were significantly lower in patients with AD than in controls (MD = −1.10, P < 0.0001; MD = −1.61, P = 0.0001, respectively). The value measured by OCTA for parafoveal superficial VD in patients with AD was also remarkably lower than that in the control group (MD = −1.42, P = 0.001), whereas there was no significant difference in the value for parafoveal deep VD (MD = −3.67, P = 0.19), compared to the controls. In addition, the foveal avascular zone (FAZ) was larger in patients with AD than in the control group (MD = 0.08, P = 0.07), although it did not reach statistical significance.

Conclusions: The present meta-analysis indicated that the macular whole enface and parafoveal vessel densities were reduced in patients with AD. Moreover, our pooled data revealed that FAZ is larger in patients with AD. Consequently, OCTA may be utilized as a diagnostic tool to identify and monitor patients with AD.