bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated DNA methylation, transcriptome and physiological analyses reveal new insights into superiority of poplars formed by interspecific grafting
Authors: Han Qingquan , Song Haifeng , Yang Congcong , Zhang Sheng , Korpelainen Helena , Li Chunyang 
Published: February 2022

Abstract
Plant grafting has a long history and it is extensively employed to improve plant performance. In our previous research, reciprocal grafts of Populus cathayana Rehder (C) and Populus deltoides Bart. Ex Marsh (D) were generated. The results showed that interspecific grafting combinations (scion/rootstock: C/D and D/C) grew better than intraspecific grafting combinations (C/C and D/D). To further understand differences in molecular mechanisms between interspecific and intraspecific grafting, we performed an integrated analysis, including bisulfite sequencing, RNA sequencing and measurements of physiological indicators, to investigate leaves of different grafting combinations. We found that the difference at the genome-wide methylation level was greater in D/C vs D/D than in C/D vs C/C, but no difference was detected at the transcription level in D/C vs D/D. Furthermore, the grafting superiority of D/C vs D/D was not as strong as that of C/D vs C/C. These results may be associated with the different methylation forms, mCHH (71.76%) and mCG (57.16%), that accounted for the highest percentages in C/D vs C/C and D/C vs D/D, respectively. In addition, the interspecific grafting superiority was found mainly related to the process of photosynthesis, phytohormone signal transduction, biosynthesis of secondary metabolites, cell wall and transcriptional regulation based on both physiological and molecular results. Overall, the results indicated that the physiological and molecular phenotypes of grafted plants are affected by the interaction between scion and rootstock. Thus, our study provides a theoretical basis for developing suitable scion–rootstock combinations for grafted plants.
Peripheral Perfusion Index as a Marker of Sepsis in Preterm Neonates
Authors: Singh Jasmine , Jain Suksham , Chawla Deepak , Randev Shivani , Khurana Supreet 
Published: February 2022

Abstract

Background
Neonatal sepsis is a major contributor to neonatal mortality in India. Blood culture, the gold standard for the diagnosis of sepsis takes 48–72 h while the serological markers have suboptimal diagnostic test characteristics. Perfusion index (PI) is a real time, non-invasive marker that can detect microcirculatory changes before other clinical manifestation of sepsis.

Objective
To determine the diagnostic accuracy of PI in detecting hospital-acquired sepsis before overt clinical manifestations.

Study design
A prospective observational study conducted in the Neonatal Intensive Care Unit (NICU) of a tertiary care hospital.

Participants
Preterm neonates admitted to NICU.

Methods
PI was continuously monitored in all enrolled neonates. Clinical sepsis was defined using the NeonatalKrankenhaus-Infektions-Surveillance-System (NeoKISS). The time of fall of PI below 0.88 and time of clinical sepsis as per NeoKISS were noted and the difference was calculated.

Results
Among 65 preterm neonates (gestational age: 31.5 ± 2.6 weeks, birth weight: 1350, IQR 1100–1700 g), a total of 86 events of suspected sepsis were noted, of which 69 were sepsis screen positive. Fifteen events were associated with culture positive sepsis. PI yielded a sensitivity of 89.47% (95% CI 78.48–96.04%), specificity of 56% (95% CI 34.93–75.60%), positive predictive value of 82.26% (95% CI 74.70–87.92%) and negative predictive value of 70% (95% CI 50.36–84.29%) in detection of hospital-acquired sepsis.

Conclusion
PI might serve as an early, non-invasive marker of hospital-acquired sepsis in preterm neonates.
Benzoxazines in the Root Exudates Responsible for Nonhost Disease Resistance of Maize to Phytophthora sojae
Authors: Liu Haixu , An Tai , Zhao Yifan , Du Xiuming , Bi Xiangqi , Zhang Zhuoqun , Chen Yufei , Wen Jingzhi 
Published: February 2022

It has been reported that the root exudates of nonhost maize inhibit Phytophthora sojae because of the presence of benzoxazines in maize roots. To understand the concentrations of benzoxazines (Bxs) in maize root exudates and the molecular mechanism of P. sojae being inhibited, the transcriptomes of P. sojae responding to three different Bxs, 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA), 6-methoxy-2-benzoxazolinone (MBOA), and benzoxazolinone (BOA), were analyzed by RNA sequencing method. We detected DIMBOA, MBOA, and BOA with a concentration range of 7 to 126 μg/ml in root exudates of three tested maize cultivars (A6565, Pengyu 1, and Xianyu 696). DIMBOA, MBOA, and BOA inhibited chemotaxis and invasiveness of P. sojae zoospores and mycelial growth. The inhibition was regulated mainly by endocytosis and the calcium signaling pathway, PI3K-Akt signaling pathway, and mTOR signaling pathway; meanwhile, the glutathione signaling pathway was activated to increase the antioxidant capacity and efflux of toxic substances. It was speculated that endocytosis plays an important role in the response of P. sojae to Bxs, and the specific functions of genes in this pathway must be further studied. This result provides new insights into the response mechanisms of P. sojae response to Bxs.
The Experience of Being a Full-Time Academic Nurse Educator During the COVID-19 Pandemic
Authors: Gazza Elizabeth A. 
Published: February 2022

Abstract

AIM
The aim of this study was to uncover the experience of being a full-time academic nurse educator (ANE) in a baccalaureate or higher degree nursing program during the COVID-19 pandemic.

BACKGROUND
In 2020, ANEs who were teaching in clinical and classroom settings, conducting in-person research, and engaging in service were suddenly required to work under new COVID-19-induced conditions.

METHOD
A hermeneutic phenomenological approach was used for the study. Personal interviews and a demographic questionnaire were utilized to collect data.

RESULTS
Fourteen ANEs participated. Five themes were uncovered through data analysis: riding a rollercoaster, figuring it out, giving and getting help, seeing silver linings, and feeling loss.

CONCLUSION
This study uncovered the experience of being an ANE during the pandemic. The findings inform strategies to enhance working conditions for current and future ANEs during the remainder of the pandemic and in post-COVID-19 nursing education.
Morganella morganii Infections in a Greek University Hospital
Authors: Maraki Sofia , Mantadakis Elpis , Spernovasilis Nikolaos , Mathioudaki Anna , Peristeris Giorgos , Alexakis Konstantinos , Kofteridis Diamantis , Samonis George 
Published: February 2022

Background

Morganella morganii is an unusual opportunistic pathogen causing often health care–associated infections mostly in patients with underlying comorbidities. Except for bacteremia, few studies on other types of infections caused by this organism are available.

Methods
The characteristics and outcome of any type of M. morganii infection treated at the University Hospital of Heraklion, Crete, Greece, between January 2013 and December 2018 were retrospectively studied.

Results
A total of 90 patients (57.8% men; mean age ± SD, 67.8 ± 21.1 years) with M. morganii infections were identified. The patients were hospitalized in medical (52.2%), surgical (25.6%), and pediatric department (4.4%), and in the intensive care unit (10%). Only 7 (7.8%) were outpatients. The most frequent were urinary tract (34.5%), and skin and soft tissues infections (33.3%). Of all cases included, 58.9% were health care-associated, whereas in 66.7%, the infection was polymicrobial. Most patients (82.2%) had at least 1 underlying comorbidity. The clinical isolates of M. morganii exhibited high susceptibility rates to carbapenems (100%), amikacin (98.9%), cefepime (94.4%), piperacillin/tazobactam (93.3%), and third-generation cephalosporins and aztreonam (90% each). The empirical treatment given was appropriate for 90% of the 82 patients with available data. Οverall and M. morganii infection–related mortality rates were 10% and 7.8%, respectively.

Conclusions
Although M. morganii infections are infrequently encountered in healthy individuals, they should be considered in inpatients with underlying comorbidities. The urinary tract, and the skin and soft tissues are the most frequently affected sites, whereas polymicrobial infections are very common. Appropriate antimicrobial treatment is associated with favorable prognosis.
HIV-1 pretreatment drug resistance negatively impacts outcomes of first-line antiretroviral treatment
Authors: Hermans Lucas E. , Hofstra Laura M. , Schuurman Rob , Ter Heine Rob , Burger David M. , Talboom Stijn A.J. , De Jong Dorien , Tempelman Hugo A. , Venter Willem D.F. , Nijhuis Monique , Wensing Annemarie M.J. 
Published: February 2022

Introduction:
Pretreatment drug resistance (PDR) prevalence in sub-Saharan Africa is rising, but evidence of its impact on efavirenz (EFV)-based antiretroviral treatment (ART) is inconclusive. We determined the impact of PDR on outcomes of EFV-based ART in a subanalysis of a randomized clinical trial comparing different ART monitoring strategies implemented at a rural treatment facility in Limpopo, South Africa.

Methods:
Participants initiating EFV-based first-line ART (2015–2017) were enrolled and received 96 weeks follow-up. Resistance to nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and non-NRTI's (NNRTIs) was retrospectively assessed by population-based sequencing. Virological failure was defined as a viral load of at least 1000 copies/ml after at least 24 weeks of ART.

Results:
A total of 207 participants were included, 60.4% (125/207) of whom were female. Median age was 38.8 (interquartile range: 31.4–46.7) years. Median CD4+ cell count was 191 (interquartile range: 70–355) cells/μl. PDR was detected in 12.9% (25/194) of participants with available sequencing results; 19 had NNRTI-resistance, and six had NRTI- and NNRTI-resistance. 26.0% of participants (40/154) with sequencing results and virological follow-up developed virological failure. PDR was independently associated with failure (adjusted hazard ratio: 3.7 [95% confidence interval: 1.68.5], P = 0.002). At failure, 87.5% (7/8) of participants with PDR harboured dual-class resistant virus, versus 16.7% (4/24) of participants without PDR (P = 0.0007). Virological resuppression after failure on first-line ART occurred in 57.7% (15/26) of participants without PDR versus 14.3% (1/7) of participants with PDR (P = 0.09).

Conclusion:
PDR was detected in 13% of study participants. PDR significantly increased the risk of virological failure of EFV-based ART. Accumulation of resistance at failure and inability to achieve virological resuppression illustrates the profound impact of PDR on treatment outcomes.
Understanding of and Trust in the Centers for Disease Control and Prevention’s Revised COVID-19 Isolation and Quarantine Guidance Among US Adults
Authors: Mishra Vishala , Dexter Joseph P. 
Published: February 2022

AbstractOn December 27, 2021 the Centers for Disease Control and Prevention (CDC) announced changes to their guidance for individuals who are exposed to or test positive for COVID-19. The revised recommendations have prompted widespread discussion of both the scientific rationale and communication strategy, including criticism from the American Medical Association.1,2 In this survey study, we assessed understanding of and trust in the CDC’s initial public statement about the new guidance among US adults.
Design and development of potent h-ACE2 derived peptide mimetics in SARS-CoV-2 Omicron variant therapeutics
Authors: Stanly Paul M. L. , Nadendla Swathi , Sobhia M Elizabeth 
Published: February 2022

ABSTRACTThe pandemic of COVID-19 has become the global health challenge due to the emergence of new variants. The Receptor binding domain (RBD) of spike protein that makes direct interaction with ACE-2 has shown unique mutated residues in most of the variants of concern (VOC). Recently WHO declared the Omicron (B.1.1.529) as VOC considering it as a highly mutated variant which includes a total of 60 mutations out of which 15 mutations occurred in RBD region of SARS-CoV-2. Inhibition of Protein-protein (Omicron RBD-h-ACE2) interaction was already proved to inhibit the viral infection. In this study, by using molecular dynamic simulations efforts are made to explore the atomistic details of Omicron RBD-h-ACE2 interaction. Based on MD simulations, h-ACE2 motif is found to be interacting with omicron RBD domain. Interaction analysis had provided key residues interacting with Omicron-RBD that helped to extract h-ACE2 peptide. Here, rational design of the peptides that have resemblance with h-ACE2 is done and the peptide library is subjected for inhibition studies against Omicron-RBD. The current study helped to identify the significant peptides that can inhibit Omicron-RBD. Altogether the performed studies will provide an opportunity to develop potential therapeutic peptidomimetics effective against Omicron variant of SARS-CoV-2.
Decoding rRNA sequences for improved metagenomics of sylvatic mosquito species
Authors: Koh Cassandra , Frangeul Lionel , Blanc Hervé , Ngoagouni Carine , Boyer Sébastien , Dussart Philippe , Grau Nina , Girod Romain , Duchemin Jean-Bernard , Saleh Maria-Carla 
Published: February 2022

ABSTRACTAs mosquito-borne virus epidemics are often preceded by undetected spillover events, surveillance and virus discovery studies in non-urban mosquitoes informs pre-emptive and responsive public health measures. RNA-seq metagenomics is a popular methodology but it is constrained by overabundant rRNA. The lack of reference sequences for most mosquito species is a major impediment against physical and computational removal of rRNA reads.We describe a strategy to assemble novel rRNA sequences from mosquito specimens, producing an unprecedented dataset of 234 full-length 28S and 18S rRNA sequences of 33 medically important species from countries with known histories of mosquito-borne virus circulation (Cambodia, the Central African Republic, Madagascar, and French Guiana). We also evaluate the utility of rRNA sequences as molecular barcodes relative to the mitochondrial cytochrome c oxidase I (COI) gene. We show that rRNA sequences can be used for species identification when COI sequences are ambiguous or unavailable, revealing evolutionary relationships concordant with contemporary mosquito systematics.This expansion of the rRNA reference library improves mosquito RNA-seq metagenomics by permitting the optimization of species-specific rRNA depletion protocols for a broader species range and streamlined species identification by rRNA barcoding. In addition, rRNA barcodes could serve as an additional tool for mosquito taxonomy and phylogeny.
Genomic and phenotypic analyses suggest moderate fitness differences among Zika virus lineages
Authors: Oliveira Glenn , Vogels Chantal B.F. , Zolfaghari Ashley , Saraf Sharada , Klitting Raphaelle , Weger-Lucarelli James , Ontiveros Carlos O. , Agarwal Rimjhim , Leon Karla P. , Tsetsarkin Konstantin A. , Harris Eva , Ebel Gregory D. , Wohl Shirlee , Grubaugh Nathan D. , Andersen Kristian G. 
Published: February 2022

AbstractRNA viruses have short generation times and high mutation rates, allowing them to undergo rapid molecular evolution during epidemics. However, the extent of RNA virus phenotypic evolution within epidemics and the resulting effects on fitness and virulence remain mostly unknown. Here, we screened the 2015-2016 Zika epidemic in the Americas for lineage-specific fitness differences. We engineered a library of recombinant viruses representing twelve major Zika virus lineages and used them to measure replicative fitness within disease-relevant human primary cells and live mosquitoes. We found that two of these lineages conferred significant in vitro replicative fitness changes among human primary cells, but we did not find fitness changes in Aedes aegypti mosquitoes. Additionally, we found evidence for elevated levels of positive selection among five amino acid sites that define major Zika virus lineages. While our work suggests that Zika virus may have acquired several phenotypic changes during a short time scale, these changes were relatively moderate and do not appear to have enhanced virulence or transmission during the epidemic.
Mutability Patterns Across the Spike Glycoprotein Reveal the Diverging and Lineage-specific Evolutionary Space of SARS-CoV-2
Authors: Rojas Chávez Roberth A. , Fili Mohammad , Han Changze , Rahman Syed A. , Bicar Isaiah G. L. , Gregory Sullivan , Hu Guiping , Das Jishnu , Brown Grant D. , Haim Hillel 
Published: February 2022

ABSTRACTMutations in the spike glycoprotein of SARS-CoV-2 allow the virus to probe the sequence space in search of higher-fitness states. New sublineages of SARS-CoV-2 variants-of-concern (VOCs) continuously emerge with such mutations. Interestingly, the sites of mutation in these sublineages vary between the VOCs. Whether such differences reflect the random nature of mutation appearance or distinct evolutionary spaces of spike in the VOCs is unclear. Here we show that each position of spike has a lineage-specific likelihood for mutations to appear and dominate descendent sublineages. This likelihood can be accurately estimated from the lineage-specific mutational profile of spike at a protein-wide level. The mutability environment of each position, including adjacent sites on the protein structure and neighboring sites on the network of comutability, accurately forecast changes in descendent sublineages. Mapping of imminent changes within the VOCs can contribute to the design of immunogens and therapeutics that address future forms of SARS-CoV-2.
Metabolic dyshomeostasis induced by SARS-CoV-2 structural proteins reveals immunological insights into viral olfactory interactions
Authors: Lachén-Montes Mercedes , Mendizuri Naroa , Ausín Karina , Echaide Miriam , Blanco Ester , Chocarro Luisa , de Toro María , Escors David , Fernández-Irigoyen Joaquín , Kochan Grazyna , Santamaría Enrique 
Published: February 2022

AbstractOne of the most common symptoms in COVID-19 is a sudden loss of smell. SARS-CoV-2 has been detected in the olfactory bulb (OB) from animal models and sporadically in COVID-19 patients. To decipher the specific role over the SARS-CoV-2 proteome at olfactory level, we characterized the in-depth molecular imbalance induced by the expression of GFP-tagged SARS-CoV-2 structural proteins (M, N, E, S) on mouse OB cells. Transcriptomic and proteomic trajectories uncovered a widespread metabolic remodeling commonly converging in extracellular matrix organization, lipid metabolism and signaling by receptor tyrosine kinases. The molecular singularities and specific interactome expression modules were also characterized for each viral structural factor. The intracellular molecular imbalance induced by each SARS-CoV-2 structural protein was accompanied by differential activation dynamics in survival and immunological routes in parallel with a differentiated secretion profile of chemokines in OB cells. Machine learning through a proteotranscriptomic data integration uncovered TGF-beta signaling as a confluent activation node by the SARS-CoV-2 structural proteome. Taken together, these data provide important avenues for understanding the multifunctional immunomodulatory properties of SARS-CoV-2 M, N, S and E proteins beyond their intrinsic role in virion formation, deciphering mechanistic clues to the olfactory inflammation observed in COVID-19 patients.
InvL, an invasin-like adhesin, is a type II secretion system substrate required for Acinetobacter baumannii uropathogenesis
Authors: Jackson-Litteken Clay D. , Di Venanzio Gisela , Le Nguyen-Hung , Scott Nichollas E. , Djahanschiri Bardya , Distel Jesus S. , Pardue Evan J. , Ebersberger Ingo , Feldman Mario F. 
Published: February 2022

ABSTRACTAcinetobacter baumannii is an opportunistic pathogen of growing concern, as isolates are commonly multidrug resistant. While A. baumannii is most frequently associated with pulmonary infections, a significant proportion of clinical isolates come from urinary sources, highlighting its uropathogenic potential. The type IIsecretion system (T2SS) of commonly used model Acinetobacter strains is important for virulence in various animal models, but the potential role of the T2SS in urinary tract infection (UTI) remains unknown. Herein, we used a catheter-associated UTI (CAUTI) model to demonstrate that a modern urinary isolate, UPAB1, requires the T2SS for full virulence. A proteomic screen to identify putative UPAB1 T2SS effectors revealed an uncharacterized lipoprotein with structural similarity to the intimin-invasin family, which serve as type Vsecretion system (T5SS) adhesins required for the pathogenesis of several bacteria. This protein, designated InvL, lacked the β-barrel domain associated with T5SSs, but was confirmed to require the T2SS for both surface localization and secretion. This makes InvL the first identified T2SS effector belonging to the intimin-invasin family. InvL was confirmed to be an adhesin, as the protein bound to extracellular matrix components and mediated adhesion to urinary tract cell lines in vitro. Additionally, the invL mutant was attenuated in the CAUTI model, indicating a role in Acinetobacter uropathogenesis. Finally, bioinformatic analyses revealed that InvL is present in nearly all clinical isolates belonging to international clone 2, a lineage of significant clinical importance. In all, we conclude that the T2SS substrate InvL is an adhesin required for A. baumannii uropathogenesis.IMPORTANCEWhile pathogenic Acinetobacter can cause various infections, we recently found that 20% of clinical isolates come from urinary sources. Despite the clinical relevance of Acinetobacter as a uropathogen, few virulence factors involved in urinary tract colonization have been defined. Herein, we identify a novel type II secretion system effector, InvL, which is required for full uropathogenesis by a modern urinary isolate. Though InvL has predicted structural similarity to the intimin-invasin family of autotransporter adhesins, InvL is predicted to be anchored to the membrane as a lipoprotein. Similar to other invasin homologs however, we demonstrate that InvL is a bona fide adhesin capable of binding extracellular matrix components and mediating adhesion to urinary tract cell lines. In all, this work establishes InvL as an adhesin important for Acinetobacter’s urinary tract virulence, and represents the first report of a type II secretion system effector belonging to the intimin-invasin family.
A quiescent resident progenitor pool is the central organizer of tendon healing
Authors: Grinstein Mor , Tsai Stephanie L , Montoro Daniel , Dingwall Heather L , Zou Ken , Sade-Feldman Moshe , Tanaka Miho J , Capellini Terence D , Rajagopal Jayaraj , Galloway Jenna L 
Published: February 2022

AbstractA tendon’s ordered extracellular matrix (ECM) is integral for transmitting force and highly prone to injury. How tendon cells, or tenocytes, embedded within this dense ECM mobilize and contribute to healing is unknown. Here, we identify a specialized Axin2+ population in mouse and human tendons that remains latent in homeostasis yet initiates the healing response and serves as a major source of tendon progenitors. Axin2+ tenocytes readily expand in vitro and express stem cell markers. In vivo, Axin2+-descendants are major functional contributors to repair: Axin2+ tenocytes proliferate, acquire injury responsive states, and re-adopt a tenocyte fate post-injury. Specific loss of Wnt secretion in Axin2+ cells alters their progenitor identity, disrupts their activation upon injury, and severely compromises any healing response. Our work highlights an unusual paradigm, wherein quiescent Axin2+ tenocytes self-regulate their identity and mobilization upon injury and provide the key initiating signal to organize a tendon-wide healing response.