bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the delivery of palliative care through predictive modeling and healthcare informatics
Authors: Murphree Dennis H , Wilson Patrick M , Asai Shusaku W , Quest Daniel J , Lin Yaxiong , Mukherjee Piyush , Chhugani Nirmal , Strand Jacob J , Demuth Gabriel , Mead David , Wright Brian , Harrison Andrew , Soleimani Jalal , Herasevich Vitaly , Pickering Brian W , Storlie Curtis B
Published: February 2021

Objective

Access to palliative care (PC) is important for many patients with uncontrolled symptom burden from serious or complex illness. However, many patients who could benefit from PC do not receive it early enough or at all. We sought to address this problem by building a predictive model into a comprehensive clinical framework with the aims to (i) identify in-hospital patients likely to benefit from a PC consult, and (ii) intervene on such patients by contacting their care team.

Materials and Methods

Electronic health record data for 68 349 inpatient encounters in 2017 at a large hospital were used to train a model to predict the need for PC consult. This model was published as a web service, connected to institutional data pipelines, and consumed by a downstream display application monitored by the PC team. For those patients that the PC team deems appropriate, a team member then contacts the patient’s corresponding care team.

Results

Training performance AUC based on a 20% holdout validation set was 0.90. The most influential variables were previous palliative care, hospital unit, Albumin, Troponin, and metastatic cancer. The model has been successfully integrated into the clinical workflow making real-time predictions on hundreds of patients per day. The model had an “in-production” AUC of 0.91. A clinical trial is currently underway to assess the effect on clinical outcomes.

Conclusions

A machine learning model can effectively predict the need for an inpatient PC consult and has been successfully integrated into practice to refer new patients to PC.
Reduced viscosity mutants of Trichoderma reesei with improved industrial fermentation characteristics
Authors: Bodie Elizabeth , Virag Aleksandra , Pratt Robert J , Leiva Nicholas , Ward Michael , Dodge Tim
Published: February 2021

Morphological mutants of Trichoderma reesei were isolated following chemical or insertional mutagenesis. The mutant strains were shown to have reduced viscosity under industrially relevant fermentation conditions and to have maintained high specific productivity of secreted protein. This allowed higher biomass concentration to be maintained during the production phase and, consequently, increased volumetric productivity of secreted protein. The causative mutations were traced to four individual genes (designated sfb3, ssb7, seb1, and mpg1). We showed that two of the morphological mutations could be combined in a single strain to further reduce viscosity and enable a 100% increase in volumetric productivity.
Pharmacists' perspectives on providing the COVID-19 vaccine in community pharmacies
Authors: Mukattash Tareq L , Jarab Anan S , Abu Farha Rana K , Nusair Mohammad B , Al Muqatash Saqer
Published: February 2021

Objectives

The objective of this study was to explore community pharmacists’ perspectives on administering COVID-19 vaccine in community pharmacies in Jordan.

Methods

Purposeful sampling was used to identify a list of 100 community pharmacies which were approached to participate in the study. Twenty-three interviews were needed to reach data saturation. In-depth interviews were conducted, recorded, transcribed and analysed using NVivo 11 software. Interviews followed a previously prepared and validated 12-item interview guide. The interview guide discussed pharmacists’ perspectives on providing the COVID-19 vaccine in community pharmacies.

Key findings

The three overarching themes which described the participating pharmacists’ views towards administrating the COVID-19 vaccine in community pharmacies were advantage, support and barriers. The reported advantages included expediting the COVID-19 vaccination process, convince people to take the vaccine, increased patient accessibility to vaccines and aiding the healthcare system in the vaccination process. Respondents indicated that they would be more willing to administer the COVID-19 vaccine if they received the needed support from the Ministry of Health and the Pharmacists Association. Furthermore, from the respondents’ perspectives, the main barriers to this practice were having no confidence in the vaccine, risk of adverse effects and lack of training and expertise.

Conclusions

Respondents reported a positive attitude towards administering the COVID-19 vaccine in community pharmacies. Respondents highlighted that they could help fighting the pandemic through administering the vaccine and expedite the vaccination process.
Suboptimal Intermediates Underlie Evolution of the Bicoid Homeodomain
Authors: Onal Pinar , Gunasinghe Himari Imaya , Umezawa Kristaley Yui , Zheng Michael , Ling Jia , Azeez Leen , Dalmeus Anecine , Tazin Tasmima , Small Stephen
Published: February 2021

Changes in regulatory networks generate materials for evolution to create phenotypic diversity. For transcription networks, multiple studies have shown that alterations in binding sites of cis-regulatory elements correlate well with the gain or loss of specific features of the body plan. Less is known about alterations in the amino acid sequences of the transcription factors (TFs) that bind these elements. Here we study the evolution of Bicoid (Bcd), a homeodomain (HD) protein that is critical for anterior embryo patterning in Drosophila. The ancestor of Bcd (AncBcd) emerged after a duplication of a Zerknullt (Zen)-like ancestral protein (AncZB) in a suborder of flies. AncBcd diverged from AncZB, gaining novel transcriptional and translational activities. We focus on the evolution of the HD of AncBcd, which binds to DNA and RNA, and is comprised of four subdomains: an N-terminal arm (NT) and three helices; H1, H2, and Recognition Helix (RH). Using chimeras of subdomains and gene rescue assays in Drosophila, we show that robust patterning activity of the Bcd HD (high frequency rescue to adulthood) is achieved only when amino acid substitutions in three separate subdomains (NT, H1, and RH) are combined. Other combinations of subdomains also yield full rescue, but with lower penetrance, suggesting alternative suboptimal activities. Our results suggest a multistep pathway for the evolution of the Bcd HD that involved intermediate HD sequences with suboptimal activities, which constrained and enabled further evolutionary changes. They also demonstrate critical epistatic forces that contribute to the robust function of a DNA-binding domain.
The metabolic origins of non-photorespiratory CO2 release during photosynthesis: a metabolic flux analysis
Authors: Xu Yuan , Fu Xinyu , Sharkey Thomas D , Shachar-Hill Yair , Walker and Berkley J
Published: February 2021

Respiration in the light (RL) releases CO2 in photosynthesizing leaves and is a phenomenon that occurs independently from photorespiration. Since RL lowers net carbon fixation, understanding RL could help improve plant carbon-use efficiency and models of crop photosynthesis. Although RL was identified more than 75 years ago, its biochemical mechanisms remain unclear. To identify reactions contributing to RL, we mapped metabolic fluxes in photosynthesizing source leaves of the oilseed crop and model plant camelina (Camelina sativa). We performed a flux analysis using isotopic labeling patterns of central metabolites during 13CO2 labeling time course, gas exchange, and carbohydrate production rate experiments. To quantify the contributions of multiple potential CO2 sources with statistical and biological confidence, we increased the number of metabolites measured and reduced biological and technical heterogeneity by using single mature source leaves and quickly quenching metabolism by directly injecting liquid N2; we then compared the goodness-of-fit between these data and data from models with alternative metabolic network structures and constraints. Our analysis predicted that RL releases 5.2 μmol CO2 g−1 FW h−1 of CO2, which is relatively consistent with a value of 9.3 μmol CO2 g−1 FW h−1 measured by CO2 gas exchange. The results indicated that ≤10% of RL results from TCA cycle reactions, which are widely considered to dominate RL. Further analysis of the results indicated that oxidation of glucose-6-phosphate to pentose phosphate via 6-phosphogluconate (the G6P/OPP shunt) can account for >93% of CO2 released by RL.
Pastoral and spiritual care for quarantined individuals and their families
Authors: Galang Joseph Renus F
Published: February 2021

A recent article showed that coronavirus disease 2019 (COVID-19) patients quarantined in isolation facilities instead of in their homes help control the spread of the virus. Given this, isolation facilities must be promoted, no matter how difficult for the patient and the family. This article recommends that pastoral and spiritual care is necessary for both the isolated individual and the family left behind. Ultimately, pastoral and spiritual care may provide a more profound kind of immunity for COVID-19 patients.
QUANTIFICATION OF PULMONARY PATHOLOGY IN CYSTIC FIBROSIS–COMPARISON BETWEEN DIGITAL CHEST TOMOSYNTHESIS AND COMPUTED TOMOGRAPHY
Authors: Meltzer C , Gilljam M , Vikgren J , Norrlund R R , Vult von Steyern K , Båth M , Johnsson Å A
Published: February 2021

Purpose: Digital tomosynthesis (DTS) is currently undergoing validation for potential clinical implications. The aim of this study was to investigate the potential for DTS as a low-dose alternative to computed tomography (CT) in imaging of pulmonary pathology in patients with cystic fibrosis (CF). Methods: DTS and CT were performed as part of the routine triannual follow-up in 31 CF patients. Extent of disease was quantified according to modality-specific scoring systems. Statistical analysis included Spearman’s rank correlation coefficient (r) and Krippendorff’s alpha (α). Major findings: The median effective dose was 0.14 for DTS and 2.68 for CT. Intermodality correlation was very strong for total score and the subscores regarding bronchiectasis and bronchial wall-thickening (r = 0.82–0.91, P < 0.01). Interobserver reliability was high for total score, bronchiectasis and mucus plugging (α = 0.83–0.93) in DTS. Conclusion: Chest tomosynthesis could be a low-dose alternative to CT in quantitative estimation of structural lung disease in CF.
Crowdfunding artists: beyond match-making on platforms
Authors: Dalla Chiesa Carolina , Dekker Erwin
Published: February 2021

This article analyzes the role that crowdfunding plays for artists who create small-scale projects. We find that artists struggle to reach new audiences and, thus, mainly use this funding tool to transform monetary gifts into reputation for their careers. Crowdfunding platforms are believed to lower transaction costs while allowing for more direct engagement between founders and funders. Instead, our study demonstrates that artists use the platform to build distance from their thick relationships and intimate networks where most of their funding originates. They hope that a successful project will help them cross the symbolic boundaries between amateur and professional realms. Despite a high success rate, most of them report not wanting to create crowdfunding campaigns again since they rarely reach other social networks. We develop these arguments to contribute to a socio-economic perspective of online funding platforms as important intermediaries in the career path of users operating at the boundary of amateur and professional production. This article contributes to developing a critical understanding of platforms, especially when users are not typical entrepreneurs or business-oriented agents but artists and do-it-yourself creators searching for funding opportunities.
Mechanisms Linking High Residential Mobility to Decreased Contraceptive Use: The Importance of Method Availability
Authors: Clark Anne C , Kusunoki Yasamin , Barber Jennifer S
Published: February 2021

While research has demonstrated that high residential mobility has negative consequences for an array of outcomes, particularly among women and young adults, the mechanisms underlying these associations are unclear. The consequences of high residential mobility may be comprised solely of a series of short-term disruptions surrounding individual moves, or there may also be long-term, cumulative effects from repeated moves. High residential mobility may diminish access to resources as individuals move to different neighborhoods, impose a cognitive burden that impairs their ability to plan ahead, or decrease the relative power they have in their relationships to limit exposure to risk behaviors. We adjudicate between these possibilities by predicting the effects of high residential mobility on sexual intercourse and contraceptive use, the proximate determinants of pregnancy, during women’s transition to adulthood. Using 2.5 years of monthly address data for 882 respondents in the Relationship Dynamics and Social Life study—a random sample of young women in Genesee County, Michigan—we find that high residential mobility is associated with long-term decreases in contraceptive use. These long-term consequences are independent of the short-term effects of individual moves and attributable to diminished contraceptive access. We disentangle the effects of home-leaving, which is distinct from subsequent moves.
Questioning corona—a study and research path
Authors: Jensen Mette , Winsløw Carl
Published: February 2021

We present a so-called ‘study and research path’, designed for advanced high school teaching in the context of a master’s thesis project, along with an outline of the mathematical and didactic background. The aim of the paper is to present and discuss an adaptation of Chevallard’s ‘paradigm of questioning the world’ to currently prevailing institutional conditions and in particular to show how mixed mathematics may be revived at a time of crisis, such as the coronavirus outbreak during which the specific design was developed.
EDTA-dependent pseudothrombocytopenia in patients with hepatosplenic schistosomiasis mansoni: a clinical management alert
Authors: Vaz de Melo Trindade Guilherme , Pereira Thiago Almeida , Caporali Júlia Fonseca de Morais , Vaz de Melo Trindade Debora , Roriz Silvana Junia , Donado Vaz de Melo Patrícia , Lambertucci José Roberto
Published: February 2021

Background

Hepatosplenic schistosomiasis mansoni (HS) is associated with thrombocytopenia. Accurate platelet counts are required for identification and management of HS patients. EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) is an in vitro phenomenon of anticoagulant-activated platelet agglutination resulting in low platelet counts by automated methods. The prevalence of EDTA-PCTP in schistosomiasis is unknown and only one case has been described. Our aims were to determine the prevalence of EDTA-PTCP in HS and evaluate alternative methods to overcome this analytical error.

Methods

Blood samples from 56 HS patients and 56 healthy volunteers were collected, and platelet counts were obtained using standard microscopy and automated (electric impedance) methods. Automated platelet counts and the presence of platelet clumps in blood smears were evaluated in samples collected in EDTA or sodium citrate tubes 20 and 180 min after blood collection.

Results

EDTA-PTCP was more frequent in HS patients than healthy volunteers (8.92% vs 0.00%, p<0.0285). Platelet clumps and PTCP were also observed in samples collected in sodium citrate tubes, refuting its use as an alternative method.

Conclusions

Automated platelet counts in blood samples from HS patients should be performed right after blood collection in EDTA tubes and verified by manual counts in blood smears.
Hepatitis delta virus-like circular RNAs from diverse metazoans encode conserved hammerhead ribozymes
Authors: de la Peña Marcos , Ceprián Raquel , Casey John L , Cervera Amelia
Published: February 2021

Human hepatitis delta virus (HDV) is a unique infectious agent whose genome is composed of a small circular RNA. Recent data, however, have reported the existence of highly divergent HDV-like circRNAs in the transcriptomes of diverse vertebrate and invertebrate species. The HDV-like genomes described in amniotes such as birds and reptiles encode self-cleaving RNA motifs or ribozymes similar to the ones present in the human HDV, whereas no catalytic RNA domains have been reported for the HDV-like genomes detected in metagenomic data from some amphibians, fish, and invertebrates. Herein, we describe the self-cleaving motifs of the HDV-like genomes reported in newts and fish, which belong to the characteristic class of HDV ribozymes. Surprisingly, HDV-like genomes from a toad and a termite show conserved type III hammerhead ribozymes, which belong to an unrelated class of catalytic RNAs characteristic of plant genomes and plant subviral circRNAs, such as some viral satellites and viroids. Sequence analyses revealed the presence of similar HDV-like hammerhead ribozymes encoded in two termite genomes, but also in the genomes of several dipteran species. In vitro transcriptions confirmed the cleaving activity for these motifs, with moderate rates of self-cleavage. These data indicate that all described HDV-like agents contain self-cleaving motifs from either the HDV or the hammerhead class. Autocatalytic ribozymes in HDV-like genomes could be regarded as interchangeable domains and may have arisen from cellular transcriptomes, although we still cannot rule out some other evolutionary explanations.
Conventional Gel Electrophoresis and TaqMan Probes Enable Rapid Confirmation of Thousand Cankers Disease from Diagnostic Samples
Authors: Stackhouse Tammy , Boggess Sarah L. , Hadziabdic Denita , Trigiano Robert N. , Ginzel Matthew D. , Klingeman William E.
Published: February 2021

Thousand cankers disease (TCD) is caused by the fungal pathogen Geosmithia morbida and vectored by the walnut twig beetle Pityophthorus juglandis. In infected walnut and butternut (Juglans spp.) hosts and wingnut species (Pterocarya spp.) hosts, tree decline and death results in ecological disruption and economic losses. A rapid molecular detection protocol for TCD using microsatellite markers can confirm the presence of insect vector or fungal pathogen DNA, but it requires specialized expensive equipment and technical expertise. Using four different experimental approaches, capillary and conventional gel electrophoresis, and traditional polymerase chain reaction (PCR) and quantitative PCR (qPCR), we describe simplified and inexpensive processes for diagnostic confirmation of TCD. The improved and rapid detection protocols reported in this study reduce time and equipment costs associated with detection of molecular pest and pathogen DNA by (1) using conventional gel electrophoresis or TaqMan molecular probes to elucidate the detection limits for G. morbida and P. juglandis DNA and (2) identifying resources that allow visualization of positive test results for infected host plant tissue samples. Conventional gel electrophoresis and TaqMan molecular probe protocols detected presence of DNA from TCD-associated fungal and insect samples. These procedural improvements can be readily adopted by diagnostic end-users and adapted for use with other complex disease systems to enable rapid pest and pathogen detection.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
A Multiplex TaqMan qPCR Assay for Detection and Quantification of Clade 1 and Clade 2 Isolates of Pseudoperonospora cubensis and Pseudoperonospora humuli
Authors: Crandall Sharifa G. , Ramon Marina L. , Burkhardt Alyssa K. , Bello Rodriguez Julian Camilo , Adair Nanci , Gent David H. , Hausbeck Mary K. , Quesada-Ocampo Lina M. , Martin Frank N.
Published: February 2021

The ability to detect and quantify aerially dispersed plant pathogens is essential for developing effective disease control measures and epidemiological models that optimize the timing for control. There is an acute need for managing the downy mildew pathogens infecting cucurbits and hop incited by members of the genus Pseudoperonospora (Pseudoperonospora cubensis clade 1 and 2 isolates and Pseudoperonospora humuli, respectively). A highly specific multiplex TaqMan quantitative polymerase chain reaction (PCR) assay targeting unique sequences in the pathogens’ mitochondrial genomes was developed that enables detection of all three taxa in a single multiplexed amplification. An internal control included in the reaction evaluated whether results were influenced by PCR inhibitors that can make it through the DNA extraction process. Reliable quantification of inoculum as low as three sporangia in a sample was observed. The multiplexed assay was tested with DNA extracted from purified sporangia, infected plant tissue, and environmental samples collected on impaction spore traps samplers. The ability to accurately detect and simultaneously quantify all three pathogens in a single multiplexed amplification should improve management options for controlling the diseases they cause.
Endophytic Microorganisms Associated with Reversion of Silverleaf Disease Symptoms in Apple
Authors: Grinbergs D. , Chilian J. , Padilla N. , Reyes M. , France A. , Moya-Elizondo E. , Gerding M.
Published: February 2021

Silverleaf is caused by the fungus Chondrostereum purpureum, which produces wood necrosis and foliar silvering in woody plants. Field observations and studies in apple have shown the reversion of foliar symptoms. Because plants were clones and received identical agronomical management, it was hypothesized that reversion is driven by endophytic microbiota. Thus, the objectives of this study were to compare healthy, diseased, and reverted plants with respect to their physiology, endophytic microbial communities, antagonistic ability of their endophytes against C. purpureum, and defense genes expression. Water potential, stomatal conductance, chlorophyll content, and fluorescence were measured. Endophytic bacterial and fungal DNA were analyzed by denaturing gradient gel electrophoresis, and community richness and similarity were calculated. Wood cores were collected and bacterial and fungal endophytes were isolated and confronted with C. purpureum-virulent strains in dual-culture assays. Defense genes expression was measured by quantitative PCR. Results indicated that there were no differences in physiological parameters between healthy and reverted plants, except for fluorescence, and both type of plants differed from diseased ones. Bacterial and fungal community richness was similar in healthy and reverted plants and higher than in diseased ones. Endophytes from reverted and healthy plants showed high antagonism to C. purpureum. Furthermore, nonexpressor of pathogenesis-related gene 1 expression was upregulated in reverted plants, whereas phenylalanine ammonia lyase and polygalacturonase-inhibiting protein genes showed higher values in diseased plants. Overall, physiological, molecular, and microbial characteristics were similar between healthy and reverted plants, and both differed from diseased ones. Therefore, reversion of symptoms is associated with changes in the endophytic microbiota, which seems to be a promising source of biological control agents against C. purpureum.
Effect of Early and Conventional Sowings on Soybean Establishment Quality, Nodulation, and Early Biomass Development Under Inoculation with Rhizoctonia solani
Authors: Lamichhane Jay Ram , Aubertot Jean-Noël
Published: February 2021

Early sowing has potential to reduce negative impacts of summer drought on soybean productivity in southern Europe. However, performing early sowing into cool and moist soil conditions may increase risks of soilborne pathogens that cause damping-off disease. We investigated whether and to what extent soybean germination, emergence, nodulation, and early biomass growth was affected when inoculated with Rhizoctonia solani, an important causal agent of damping-off disease. We conducted this study through four complementary approaches: (i) in vitro laboratory tests, (ii) field experiments including two sowing dates (early and conventional), (iii) growth-chamber experiments, and (iv) modeling. The pathogen caused disease symptoms and significantly reduced (P ≤ 0.001) radicle growth in vitro but failed to cause disease under field or growth-chamber conditions. No biological suppressiveness of the field soil to R. solani was found when tested in the growth chamber. Final field emergence rates ranged from 72 to 92% for early and conventional sowing, respectively, while those in the growth chamber ranged from 80 to 100%. Under field conditions, abiotic stresses were the major causes of nonemergence while biotic stresses had only minor impact on seedling emergence. A significant effect of sowing date (P < 0.001) was observed on the average shoot and root length and on the number of average nodules per plantlet. The overall prediction quality of the SIMPLE model was very good for both sowing dates. The contrasts between laboratory and field experiments in terms of disease development, time to emergence, and early growth parameters are discussed.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
MdBVe46 is an envelope protein that is required for virion formation by Microplitis demolitor bracovirus
Authors: Arvin Michael J. , Lorenzi Ange , Burke Gaelen R. , Strand Michael R.
Published: February 2021

Bracoviruses (BVs) are endogenized nudiviruses that braconid parasitoid wasps have coopted for functions in parasitizing hosts. Microplitis demolitor is a braconid wasp that produces Microplitis demolitor bracovirus (MdBV) and parasitizes the larval stage of the moth Chrysodeixis includens. Some BV core genes are homologs of genes also present in baculoviruses while others are only known from nudiviruses or other BVs. In this study, we had two main goals. The first was to separate MdBV virions into envelope and nucleocapsid fractions before proteomic analysis to identify core gene products that were preferentially associated with one fraction or the other. Results indicated that nearly all MdBV baculovirus-like gene products that were detected by our proteomic analysis had similar distributions to homologs in the occlusion-derived form of baculoviruses. Several core gene products unknown from baculoviruses were also identified as envelope or nucleocapsid components. Our second goal was to functionally characterize a core gene unknown from baculoviruses that was originally named HzNVorf64-like. Immunoblotting assays supported our proteomic data that identified HzNVorf64-like as an envelope protein. We thus renamed HzNVorf64-like as MdBVe46, which we further hypothesized was important for infection of C. includens. Knockdown of MdBVe46 by RNA interference (RNAi) greatly reduced transcript and protein abundance. Knockdown of MdBVe46 also altered virion morphogenesis, near-fully inhibited infection of C. includens, and significantly reduced the proportion of hosts that were successfully parasitized by M. demolitor.
Loss of the virulence plasmid by Shigella sonnei promotes its interactions with CD207 and CD209 receptors
Authors: Wu Bi-cong , Olivia Njiri A. , Tembo John Mambwe , He Ying-xia , Zhang Ying-miao , Xue Ying , Ye Cheng-lin , Lv Yin , Li Wen-jin , Jiang Ling-Yu , Huo Xi-xiang , Sun Zi-yong , Chen Zhong-ju , Qin Ji-chao , Li An-yi , Park Chae Gyu , Klena John D. , Ding Hong-hui , Chen Tie
Published: February 2021

Introduction.
Shigella sonnei, the cause of bacillary dysentery, belongs to Gram-negative enteropathogenic bacteria.

S. sonnei

contains a 210 kb virulence plasmid that encodes an O-antigen gene cluster of LPSs. However, this virulence plasmid is frequently lost during replication. It is well-documented that after losing the O-antigen and becoming rough strains, the Gram-negative bacteria may express an LPS core on its surface. Previous studies have suggested that by using the LPS core, Gram-negative bacteria can interact with several C-type lectin receptors that are expressed on antigen-presenting cells (APCs).

Hypothesis/Gap Statement.

S. sonnei

by losing the virulence plasmid may hijack APCs via the interactions of LPS-CD209/CD207.

Aim. This study aimed to investigate if the

S. sonnei

rough strain, by losing the virulence plasmid, interacted with APCs that express C-type lectins of human CD207, human CD209a and mouse CD209b.

Methodology. SDS-PAGE silver staining was used to examine the O-antigen expression of

S. sonnei

WT and its rough strain. Invasion assays and inhibition assays were used to examine the ability of

S. sonnei

WT and its rough strain to invade APCs and investigate whether CD209 and CD207 are receptors for phagocytosis of rough

S. sonnei

. Animal assays were used to observe the dissemination of

S. sonnei

.

Results.

S. sonnei

did not express O-antigens after losing the virulence plasmid. The

S. sonnei

rough strain invades with APCs, including human dendritic cells (DCs) and mouse macrophages. CD209 and CD207 are receptors for phagocytosis of rough

S. sonnei

. Expression of the O-antigen reduces the ability of the

S. sonnei

rough strain to be disseminated to mesenteric lymph nodes and spleens.

Conclusion. This work demonstrated that

S. sonnei

rough strains – by losing the virulence plasmid – invaded APCs through interactions with CD209 and CD207 receptors.
Mining indigenous honeybee gut microbiota for Lactobacillus with probiotic potential
Authors: Aziz Ghazal , Tariq Muhammad , Zaidi Arsalan Haseeb
Published: February 2021

The present study was done to explore the diversity of lactic acid bacteria (LAB) associated with the gastrointestinal tract (GIT) of honeybee species endemic to northeastern Pakistan. Healthy worker bees belonging to Apis mellifera, A. dorsata, A. cerana and A. florea were collected from hives and the surroundings of a major apiary in the region. The 16S rRNA amplicon sequencing revealed a microbial community in A. florea that was distinct from the others in having an abundance of

Lactobacillus

and Bifidobacteria. However, this was not reflected in the culturable bacteria obtained from these species. The isolates were characterized for safety parameters, and 20 LAB strains deemed safe were evaluated for resistance to human GIT stresses like acid and bile, adhesion and adhesiveness, and anti-pathogenicity. The five most robust strains,

Enterococcus saigonensis

NPL780a,

Lactobacillus rapi

NPL782a,

Lactobacillus kunkeei

NPL783a, and NPL784, and

Lactobacillus paracasei

NPL783b, were identified through normalized Pearson (n) principal components analysis (PCA). These strains were checked for inhibition of human pathogens, antibiotic resistance, osmotic tolerance, metabolic and enzymatic functions, and carbohydrate utilization, along with antioxidative and cholesterol-removing potential. The findings suggest at least three strains (NPL 783a, 784 and 782a) as candidates for further in vitro and in vivo investigations of their potential health benefits and application as novel probiotic adjuncts.
Confirmation of an Inverse Relationship between Bioaerosol Count and Influenza-like Illnesses, Including COVID-19. On the Contribution of Mold Spores
Authors: Shah Richa B. , Shah Rachna D. , Retzinger Damien G. , Retzinger Andrew C. , Retzinger Deborah A. , Retzinger Gregory S.
Published: February 2021

Data from Chicago confirm the end of flu season coincides with the beginning of pollen season. The end of flu season also coincides with onset of seasonal aerosolization of mold spores. Overall, the data suggest bioaerosols, especially mold spores, compete with viruses for a shared receptor, with the periodicity of influenza-like illnesses, including COVID-19, a consequence of seasonal factors that influence aerosolization of competing species.
Investigation of Autosomal Genetic Sex Differences in Parkinson’s disease
Authors: Blauwendraat Cornelis , Iwaki Hirotaka , Makarious Mary B. , Bandres-Ciga Sara , Leonard Hampton , Grenn Francis P. , Lake Julie , Krohn Lynne , Tan Manuela , Kim Jonggeol Jeff , Gibbs Jesse Raphael , Hernandez Dena G. , Ruskey Jennifer A. , Pihlstrøm Lasse , Toft Mathias , van Hilten Jacobus J. , Marinus Johan , Schulte Claudia , Brockmann Kathrin , Sharma Manu , Siitonen Ari , Majamaa Kari , Eerola-Rautio Johanna , Tienari Pentti J. , Grosset Donald , Lesage Suzanne , Corvol Jean-Christophe , Brice Alexis , Wood Nick , Hardy John , Gan-Or Ziv , Heutink Peter , Gasser Thomas , Morris Huw , Noyce Alastair J. , Nalls Mike A. , Singleton Andrew B.
Published: February 2021

Parkinson’s disease (PD) is a complex neurodegenerative disorder. Males are on average ∼1.5 times more likely to develop PD compared to females. Over the years genome-wide association studies (GWAS) have identified numerous genetic risk factors for PD, however it is unclear whether genetics contribute to disease etiology in a sex-specific manner.

In an effort to study sex-specific genetic factors associated with PD, we explored two large genetic datasets from the International Parkinson’s Disease Genomics Consortium and the UK Biobank consisting of 13,020 male PD cases, 7,936 paternal proxy cases, 89,660 male controls, 7,947 female PD cases, 5,473 maternal proxy cases and 90,662 female controls. We performed GWAS meta-analyses to identify distinct patterns of genetic risk contributing to disease in male versus female PD cases.

In total 19 genome-wide significant regions were identified, and no sex-specific effects were observed. A high genetic correlation between the male and female PD GWASes was identified (rg=0.877) and heritability estimates were identical between male and female PD cases (∼20%).

We did not detect any significant genetic differences between male or female PD cases. Our study does not support the notion that common genetic variation on the autosomes could explain the difference in prevalence of PD between males and females at least when considering the current sample size under study. Further studies are warranted to investigate the genetic architecture of PD explained by X and Y chromosomes and further evaluate environmental effects that could potentially contribute to PD etiology in male versus females.
Anterior nasal versus nasal mid-turbinate sampling for a SARS-CoV-2 antigen-detecting rapid test: does localisation or professional collection matter?
Authors: Nikolai Olga , Rohardt Chiara , Tobian Frank , Junge Andrea , Corman Victor M. , Jones Terry C. , Gaeddert Mary , Lainati Federica , Sacks Jilian A. , Seybold Joachim , Mockenhaupt Frank P. , Denkinger Claudia M. , Lindner Andreas K.
Published: February 2021

Objectives

The aim of this diagnostic accuracy study was direct comparison of two different nasal sampling methods for an antigen-based rapid diagnostic test (Ag-RDT) that detects severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furthermore, the accuracy and feasibility of self-sampling was evaluated.

Methods

This manufacturer-independent, prospective diagnostic accuracy study, compared professional anterior nasal (AN) and nasal mid-turbinate (NMT) sampling for a WHO-listed SARS-CoV-2 Ag-RDT. A second group of participants collected a NMT sample themselves and underwent a professional nasopharyngeal swab for comparison. The reference standard was real-time polymerase chain reaction (RT-PCR) using combined oro-/nasopharyngeal sampling. Individuals with high suspicion of SARS-CoV-2 infection were tested. Sensitivity, specificity, and percent agreement were calculated. Self-sampling was observed without intervention. Feasibility was evaluated by observer and participant questionnaires.

Results

Among 132 symptomatic adults, both professional AN- and NMT-sampling yielded a sensitivity of 86.1% (31/36 RT-PCR positives detected; 95%CI: 71.3-93.9) and a specificity of 100.0% (95%CI: 95.7-100). The positive percent agreement (PPA) was 100% (95%CI: 89.0-100). Among 96 additional adults, self NMT- and professional NP-sampling yielded an identical sensitivity of 91.2% (31/34; 95%CI 77.0-97.0). Specificity was 98.4% (95%CI: 91.4-99.9) with NMT- and 100.0% (95%CI: 94.2-100) with NP-sampling. The PPA was 96.8% (95%CI: 83.8-99.8). Most participants (85.3%) considered self-sampling as easy to perform.

Conclusion

Professional AN- and NMT-sampling are of equivalent accuracy for an Ag-RDT in ambulatory symptomatic adults. Participants were able to reliably perform the NMT-sampling themselves, following written and illustrated instructions. Nasal self-sampling will likely facilitate scaling of SARS-CoV-2 antigen testing.
SARS-CoV2- infection as a trigger of humoral response against apolipoprotein A-1
Authors: Pagano Sabrina , Yerly Sabine , Meyer Benjamin , Juillard Catherine , Suh Noémie , Terrier Christophe Le , Daguer Jean-Pierre , Farrera-Soler Lluc , Barluenga Sofia , Piumatti Giovanni , Hartley Oliver , Lemaitre Barbara , Eberhardt Christiane S. , Siegrist Claire-Anne , Eckerle Isabella , Stringhini Silvia , Guessous Idris , Kaiser Laurent , Pugin Jerome , Winssinger Nicolas , Vuilleumier Nicolas
Published: February 2021

Aims

Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights in the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. We aimed at determining i) the association between anti-SARS-CoV-2 and anti-apoA-1 humoral response, ii) their relationship to prognosis, and iii) the degree of linear homology between SARS-CoV-2, apoA-1, and Toll-like receptor-2 (TLR2) epitopes.

Methods and Results

Immunoreactivity against different engineered peptides as well as cytokines were assessed by immunoassays, on a case-control (n=101), an intensive care unit (ICU; n=126) with a 28-days follow-up, and a general population cohort (n=663) with available samples in the pre and post-pandemic period. Using bioinformatics modelling a linear sequence homologies between apoA-1, TLR2, and Spike epitopes were identified. Overall, anti-apoA-1IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (p<0.0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2IgG, cytokines, and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-days kinetics, reaching 82% for anti-apoA-1 seropositivity. C-statistics (CS) indicated that anti-Spike/TLR2 mimic-peptide IgGs displayed a significant prognostic accuracy for overall mortality at 28 days (CS: 0.64; p=0.02). In the general population, SARS-CoV-2 exposure increased baseline anti-apoA-1 IgG levels.

Conclusion

COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.
Machine Learning with Objective Serum Markers and Algorithmic Deep Learning Computed Tomography Scan Analysis for Classification of Brain Injury
Authors: Rafter Daniel , Li Zhuliu , Schaaf Tory , Gault Kristen , Thorpe Maxwell , Venkatesh Shivani , Edpuganti Radhika , Song Tianci , Kuang Rui , Samadani Uzma
Published: February 2021

Background

Brain injury is pathophysiologically diverse, with many cases presenting with mixed pathologies. Utilizing objective measures to investigate the pathophysiology of injury would aid in understanding prognosis and targeting therapeutics.

Objective

The goal of this study is to develop a traumatic brain injury classification scheme based on open source deep learning computer tomography (CT) analysis and the two serum biomarkers, glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal L1 (UCH-L1).

Methods

Machine learning was utilized to develop a novel algorithm capable of classifying the type of brain injury based on a CT scan analysis algorithm and GFAP and UCH-L1 concentrations. Injury was stratified into one of four groups: spontaneous hemorrhage, oxygen deprivation, trauma resulting in vascular injury or high-velocity trauma with negative CT scan.

Outcomes

100 research subjects were enrolled. Using a combination of CT analysis and serum markers, the subjects with CT positive trauma were distinguishable from those with spontaneous hemorrhage, ischemic injury, CT negative trauma and controls with AUCs of 0.96, 0.99., 0.98 and 1.00 respectively. Ischemic injury was distinguishable from CT positive trauma with an AUC of 0.98. All forms of brain injury could be distinguished from controls with AUC = 1.00.

Discussion

An open source algorithmic CT scan analysis algorithm and serum biomarkers accurately classified the nature of brain injury across major etiologies. Further implementation of such algorithms and addition of other objective measures will enable better prognostication of injury and improved development of therapeutics.
Prevalence of cardiovascular risk factors in osteoarthritis patients derived from primary care records: a systematic review of observational studies
Authors: Huang Xiaoyang , Wilkie Ross , Mamas Mamas A , Yu Dahai
Published: February 2021

Background

People with osteoarthritis are at a high risk of cardiovascular disease (CVD). Detecting CVD risk factors in this high-risk population will help to improve CVD outcomes. Primary care electronic health records (EHRs) provide opportunities for the surveillance of CVD risk factors in the osteoarthritis population. This paper aimed to systematically review evidence of prevalence estimates of CVD risk factors in people with osteoarthritis derived from primary care EHRs.

Methods

Eight databases including MEDLINE were systematically searched to January 2019. Observational studies using primary care EHRs data to estimate the prevalence of six CVD risk factors in people with osteoarthritis were included. A narrative review was conducted to summarise study results.

Results

Six studies were identified. High heterogeneity between studies prevented the calculation of pooled estimates. One study reported the prevalence of smoking (12.5%); five reported hypertension (range: 19.7%-55.5%); four reported obesity (range: 34.4%-51.6%); two reported dyslipidaemia (6.0%, 13.3%); five reported diabetes (range: 5.2%-18.6%); and one reported chronic kidney disease (1.8%) in people with osteoarthritis. One study reported a higher prevalence of hypertension (Odds Ratio (OR) 1.25, 95% confidence interval (CI) 1.19-1.32), obesity (OR 2.44, 95%CI 2.33-2.55), dyslipidaemia (OR 1.24, 95%CI 1.14-1.35) and diabetes (1.11, 95%CI 1.02-1.22) in the osteoarthritis population compared with the matched non-osteoarthritis population.

Conclusions

From studies identified in this review that had used primary care EHRs, prevalence estimates of CVD risk factors were higher in people with osteoarthritis compared with those without. These estimates may provide baseline frequency of CVD risk factors in osteoarthritis patients in primary care, although this is limited by the small number of studies and high heterogeneity. Further studies of frequency, using primary care EHRs, will help to answer whether this data source can be used for evaluating approaches to manage CVD risk factors in osteoarthritis patients.

Subject Area

Primary care research
A surrogate virus neutralization test to quantify antibody-mediated inhibition of SARS-CoV-2 in finger stick dried blood spot samples
Authors: Sancilio Amelia , D’Aquila Richard , McNally Elizabeth M. , Velez Matt E , Ison Michael G. , Demonbreun Alexis R. , McDade Thomas W.
Published: February 2021

Background

The spike protein of SARS-CoV-2 engages the human angiotensin-converting enzyme 2 (ACE2) receptor to enter host cells, and neutralizing antibodies are effective at blocking this interaction to prevent infection. Widespread application of this important marker of protective immunity is limited by logistical and technical challenges associated with live virus methods and venous blood collection. To address this gap, we validated an immunoassay-based method for quantifying neutralization of the spike-ACE2 interaction in a single drop of capillary whole blood, collected on filter paper as a dried blood spot (DBS) sample.

Methods

Samples are eluted overnight and incubated in the presence of spike antigen and ACE2 in a 96-well solid phase plate. Competitive immunoassay with electrochemiluminescent label is used to quantify neutralizing activity. The following measures of assay performance were evaluated: dilution series of confirmed positive and negative samples, agreement with results from matched DBS-serum samples, analysis of results from DBS samples with known COVID-19 status, and precision (intra-assay percent coefficient of variation; %CV) and reliability (inter-assay; %CV).

Results

Dilution series produced the expected pattern of dose-response. Agreement between results from serum and DBS samples was high, with concordance correlation = 0.991. Analysis of three control samples across the measurement range indicated acceptable levels of precision and reliability. Median % neutralization was 46.9 for PCR confirmed convalescent COVID-19 samples and 0.1 for negative samples.

Conclusions

Large-scale testing is important for quantifying neutralizing antibodies that can provide protection against COVID-19 in order to estimate the level of immunity in the general population. DBS provides a minimally-invasive, low cost alternative to venous blood collection, and this scalable immunoassay-based method for quantifying neutralization of the spike-ACE2 interaction can be used as a surrogate for virus-based assays to expand testing across a wide range of settings and populations.
Soluble guanylate cyclase stimulation mitigates skeletal and cardiac muscle dysfunction in a mdx model of Duchenne muscular dystrophy
Authors: Zhang Ling , Xu Yuanyuan , Yousefi Keyvan , Irion Camila I. , Alvarez Roger A. , Krishnan Shalini M. , Stasch Johannes-Peter , Martinez Eliana C. , Buys Emmanuel S. , Sandner Peter , Shehadeh Lina A. , Percival Justin M.
Published: February 2021

The impairment of neuronal nitric oxide synthase (nNOS) signaling contributes to disease pathology in the muscle wasting disorder Duchenne muscular dystrophy (DMD). nNOS signal propagation occurs through nitric oxide sensitive soluble guanylate cyclase (sGC), a critical source of cyclic guanosine monophosphate (cGMP) in muscle. Although both nNOS and sGC activity are impaired in DMD patients, little is known about sGC as a therapeutic target. In this study, we tested the hypothesis that stimulating sGC activity with the allosteric agonist BAY41-8543 mitigates striated muscle pathology in the mdx4cv mouse model of DMD. In contrast to DMD patients, mdx mice exhibited greater basal sGC activity than wild type controls with preservation of cGMP levels due partly to upregulation of sGC in some muscles. Stimulating sGC activity in mdx mice with BAY41-8543 substantially reduced skeletal muscle damage, macrophage densities and inflammation and significantly increased resistance to contraction-induced fatigue. BAY41-8543 also enhancedin vivodiaphragm function while reducing breathing irregularities suggesting improved respiratory function. BAY41-8543 attenuated cardiac hypertrophic remodeling, fibrosis and diastolic dysfunction including left atrium enlargement in aged mdx mice. Overall, sGC stimulation significantly mitigated skeletal and cardio-respiratory dysfunction in mdx4cv mice. Importantly, this study provides compelling pre-clinical evidence supporting sGC as a novel target in DMD and the repurposing of FDA-approved sGC stimulators, such as riociguat and veraciguat, as a novel therapeutic approach for DMD.