bluuebunny/crossref_metadata_2025_split huggingface dataset:
PM2.5 induces inflammatory responses via oxidative stress-mediated mitophagy in human bronchial epithelial cells
Authors: Zhai Xuedi , Wang Jianshu , Sun Jiaojiao , Xin Lili 
Published: January 2022

Abstract

Background
Fine particulate matter (PM2.5) is a ubiquitous air pollutant, and it has been reported to be closely associated with lung inflammatory injury. In this study, the potential molecular mechanisms underlying PM2.5-induced cellular inflammation in human bronchial epithelial (BEAS-2B) cells were investigated.

Materials and methods
Ambient PM2.5 particulates from Suzhou, China, were collected and re-suspended in ultrapure water. Cellular damages, characterized by oxidative stress, mitochondrial injury, and inflammatory cytokine production, were determined in 24 h PM2.5-treated BEAS-2B cells with or without 3-methyladenine (3-MA; autophagy inhibitor) pretreatment. Biomarkers related to oxidative damage, inflammatory injury and autophagy signaling pathways were also measured.

Results
Uptake of PM2.5 in BEAS-2B cells induced cellular oxidative damage, mitochondrial injury, and inflammatory responses as indicated by a significant decrease in GSH/GSSG ratio, increased MDA content, dilated mitochondria with loss and rupture of crista, and production of inflammatory cytokines. Activation of Nrf-2/TXNIP-mediated NF-κB and Bnip3L/NIX-dependent mitophagy signaling pathways, as well as accumulation of autophagosomes and autolysosomes, were also observed. A 6 h pretreatment of 3-MA increased PM2.5-induced oxidative damage and cellular inflammation as indicated by increasing protein levels of HO-1, TXNIP, Bnip3L/NIX and IL-8 gene expression.

Conclusions
PM2.5 induced cellular inflammatory injury by oxidative stress, mitochondrial dysfunction, and mitophagy initiation. Although induction of Bnip3L/NIX-mediated mitophagy in BEAS-2B cells appeared to confer protection in response to PM2.5, dysfunction of autophagic flux may be a critical contributor to defective mitophagy and cellular inflammatory response.
Genome-wide DNA N6-adenine methylation in sea buckthorn (Hippophae rhamnoides L.) fruit development
Authors: Zhang Guoyun , Diao Songfeng , Song Yating , He Caiyun , Zhang Jianguo 
Published: January 2022

Abstract
As a new epigenetic mark, DNA N6-adenine (6mA) methylation plays an important role in various biological processes and has been reported in many prokaryotic organisms in recent years. However, the distribution patterns and functions of DNA 6mA modification have been poorly studied in non-model crops. In this study, we observed that the methylation ratio of 6mA was about 0.016% in the sea buckthorn (Hippophae rhamnoides L.) genome using mass spectrometry. We first constructed a comprehensive 6mA landscape in sea buckthorn genome using nanopore sequencing at single-base resolution. Distribution analysis suggested that 6mA methylated sites were widely distributed in the sea buckthorn chromosomes, which were similar to those in Arabidopsis and rice. Furthermore, reduced 6mA DNA methylation is associated with different expression of genes related to the fruit-ripening process in sea buckthorn. Our results revealed that 6mA DNA modification could be considered an important epigenomic mark and contributes to the fruit ripening process in plants.
Developmental Care Practice and Documentation Variability in the Cardiac ICU
Authors: Miller Thomas A. , Elhoff Justin J. , Alexander Nneka M. , Butler Samantha C. , Uzark Karen C. , Glotzbach Kristi L. , Mahle William T. , Lisanti Amy J. 
Published: January 2022

OBJECTIVES:
Describe variability in developmental care practices, as documented in the electronic health record, for infants undergoing congenital heart surgery.

DESIGN:
Multicenter, retrospective, cohort study.

SETTING:
Six pediatric cardiac centers.

PATIENTS:
One hundred eighty-two infants undergoing one of three index operations: Norwood palliation, aortic arch reconstruction with ventricular septal defect closure, or arterial switch.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Core domains of developmental care encompassing pain assessment, feeding, infant holding, caregiver involvement, therapy, and psychosocial services were reviewed. Practices varied across individuals, institutions, and the hospital stay. At five of six sites, greater than 90% of individuals had physical or occupational therapy services as part of their care, but the day of first evaluation ranged from day of admission to postoperative day 28. Similar patterns were seen in feeding team and social work involvement. Consistent documentation of developmental care was dependent on the domain and site. Of the total days reviewed (n = 1,192), pain scores were documented in 95%. In those same days, documentation of whether or not a patient was out of the crib to be held varied by site from 11% to 93%. Type of oral feeding, breast versus bottle, was documented on the day prior to discharge 48% of the time.

CONCLUSIONS:
There are significant, quantifiable variations in documented developmental care practices at both the individual and site level. More reliable documentation of developmental care practices is required to associate these variables with later outcomes and investigate disparities in individualized developmental care practices.
Sexual History Documentation and Sexually Transmitted Infection Screening for Mental Health Patients in a Pediatric Emergency Department
Authors: Ekstrom Joanna , Alfath Zineb , Schneider Kari 
Published: January 2022

ObjectivesAdolescents with psychiatric conditions more commonly engage in high-risk sexual behaviors and are at increased risk of sexually transmitted infections (STIs) and when presenting to pediatric emergency departments (PEDs) may be an important population in which to target screening efforts. This study aimed to determine frequency of physician-documented sexual history and STI screening in adolescents presenting to a PED with mental health-related complaints.MethodsRetrospective study of patients aged 14 to 18 years presenting to a PED February 2015 to September 2016. Electronic records were reviewed for demographics, chief complaint, sexual history documentation, STI screening, resident involvement in patient care, and disposition. Proportions were calculated for frequencies, whereas χ2and Fisher exact tests evaluated factors associated with documentation of sexual history and STI screening.ResultsTwo hundred eighty-five patient encounters were identified. Age range was 15 to 18 years with an average of 16 years, and 58% were girls. The most common chief complaint was “intentional ingestion/overdose” (169 encounters, 59%) followed by “suicidal/attempted suicide” (59, 21%). Seventy-seven patients (27%) had sexual history documented. Girls were more likely to have sexual history documented (75% vs 52%,P= 0.0004). Forty-five (59%) patients were noted to be sexually active, and 17 (38%) of these were screened for STI. There was no relationship between screening and race, sex, or involvement of a resident in patient care.ConclusionsIn a high-risk PED population, physicians documented sexual history only 27% of the time. Female patients were more likely to have a sexual history documented. In patients with sexual history indicating risk for STI, less than half were screened.
The Pocket Flap: A Pericranial Galeal-Frontalis Flap for Lining and Graft Coverage in Nasal Reconstruction
Authors: Pfaff Miles J. , Muetterties Corbin , Nahabet Edward , Roostaeian Jason 
Published: January 2022

Abstract
Complex nasal defects can necessitate nasal lining, bone and cartilage, and skin reconstruction. Defects requiring lining and structural support without the need for skin resurfacing are relatively uncommon. The following case report describes in detail a pericranial galeal-frontalis flap that is used to both reconstruct the nasal lining and provide adequate cartilage graft coverage. The pericranial galeal-frontalis flap provides yet another option for the reconstructive surgeon faced with complex defects of the nasal dorsum.
Mediation analysis to inform policy on coronary revascularization by expected time to treatment: Analytical framework
Authors: Sobolev Boris , Kuramoto Lisa 
Published: January 2022

ABSTRACTObjectivesClinical guidelines favour coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI) for patients with stable complex coronary disease. Yet the benefit of CABG as established in trials may not be generalizable to populations in which treatment method determines time to treatment, typically being longer for CABG. For cases in which the cardiac anatomy is suitable for either treatment, it is unclear whether it is appropriate to recommend CABG, which is likely to be delayed, if PCI can be performed sooner. This paper outlines an analytical framework for a policy analysis of the timing of coronary revascularization.MethodsWe constructed a thought experiment to examine whether time to treatment will influence the advantage of CABG. We substantiated the use of mediation analysis to estimate the extent to which differences in outcomes between CABG and PCI would change if times to CABG were the same as times to PCI.ResultsWe designed a study that uses data from a population-based patient registry to obtain effect measures of mediation analysis: the total effect, the natural indirect effect, and the natural direct effect. The partitioning of the total effect will allow us to estimate the proportional reduction in the risk of an outcome if the time to CABG was similar to that of PCI.InterpretationTreatment recommendation, resource allocation and scheduling benchmarks will be guided by understanding the extent to which the time to treatment mediates the relation between revascularization method and outcome.
Statistical Inference Using GLEaM Model with Spatial Heterogeneity and Correlation between Regions
Authors: Tan Yixuan , Zhang Yuan , Cheng Xiuyuan , Zhou Xiao-Hua 
Published: January 2022

AbstractA better understanding of the various patterns in the coronavirus disease 2019 (COVID-19) spread in different parts of the world is crucial to its prevention and control. Motivated by the celebrated GLEaM model (Balcan et al., 2010[1]), this paper proposes a pioneering stochastic dynamic model to depict the evolution of COVID-19. The model allows spatial and temporal heterogeneity of transmission parameters and involves transportation between regions. Based on the proposed model, this paper also designs a two-step procedure for parameter inference, which utilizes the correlation between regions through a prior distribution that imposes graph Laplacian regularization on transmission parameters. Experiments on simulated data and real-world data in China and Europe indicate that the proposed model achieves higher accuracy in predicting the newly confirmed cases than baseline models.
An in vitro and in vivo approach for the isolation of Omicron variant from human clinical specimens
Authors: Yadav Pragya D. , Gupta Nivedita , Potdar Varsha , Mohandas Sreelekshmy , Sahay Rima R. , Sarkale Prasad , Shete Anita M. , Razdan Alpana , Patil Deepak Y. , Nyayanit Dimpal A. , Joshi Yash , Patil Savita , Majumdar Triparna , Dighe Hitesh , Malhotra Bharti , Shastri Jayanthi , Abraham Priya 
Published: January 2022

AbstractDue to failure of virus isolation of Omicron variant in Vero CCL-81 from the clinical specimen’s of COVID-19 cases, we infected Syrian hamsters and then passage into Vero CCL-81 cells. The Omicron sequences were studied to assess if hamster could incorporate any mutation to changes its susceptibility. L212C mutation, Tyrosine 69 deletion, and C25000T nucleotide change in spike gene and absence of V17I mutation in E gene was observed in sequences of hamster passage unlike human clinical specimen and Vero CCL-81 passages. No change was observed in the furin cleavage site in any of the specimen sequence which suggests usefulness of these isolates in future studies.
The hyper-transmissible SARS-CoV-2 Omicron variant exhibits significant antigenic change, vaccine escape and a switch in cell entry mechanism
Authors: Willett Brian J. , Grove Joe , MacLean Oscar A. , Wilkie Craig , Logan Nicola , Lorenzo Giuditta De , Furnon Wilhelm , Scott Sam , Manali Maria , Szemiel Agnieszka , Ashraf Shirin , Vink Elen , Harvey William T. , Davis Chris , Orton Richard , Hughes Joseph , Holland Poppy , Silva Vanessa , Pascall David , Puxty Kathryn , da Silva Filipe Ana , Yebra Gonzalo , Shaaban Sharif , Holden Matthew T. G. , Pinto Rute Maria , Gunson Rory , Templeton Kate , Murcia Pablo R. , Patel Arvind H. ,   The COVID-19 Genomics UK (COG-UK) Consortium, Haughney John , Robertson David L. , Palmarini Massimo , Ray Surajit , Thomson Emma C. 
Published: January 2022

AbstractVaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron, the fifth VOC to be described, harbours 30 amino acid mutations in spike including 15 in the receptor-binding domain. Here, we demonstrate substantial evasion of neutralisation by Omicronin vitrousing sera from vaccinated individuals. Importantly, these data are mirrored by a substantial reduction in real-world vaccine effectiveness that is partially restored by booster vaccination. We also demonstrate that Omicron does not induce cell syncytia and favours a TMPRSS2-independent endosomal entry pathway. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant.
The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources
Authors: DiStefano Marina T. , Goehringer Scott , Babb Lawrence , Alkuraya Fowzan S. , Amberger Joanna , Amin Mutaz , Austin-Tse Christina , Balzotti Marie , Berg Jonathan S. , Birney Ewan , Bocchini Carol , Bruford Elspeth A. , Coffey Alison J. , Collins Heather , Cunningham Fiona , Daugherty Louise C. , Einhorn Yaron , Firth Helen V. , Fitzpatrick David R. , Foulger Rebecca E. , Goldstein Jennifer , Hamosh Ada , Hurles Matthew R. , Leigh Sarah E. , Leong Ivone US. , Maddirevula Sateesh , Martin Christa L. , McDonagh Ellen M. , Olry Annie , Puzriakova Arina , Radtke Kelly , Ramos Erin M. , Rath Ana , Riggs Erin Rooney , Roberts Angharad M. , Rodwell Charlotte , Snow Catherine , Stark Zornitza , Tahiliani Jackie , Tweedie Susan , Ware James S. , Weller Phillip , Williams Eleanor , Wright Caroline F. , Yates T Michael. , Rehm Heidi L. 
Published: January 2022

PURPOSESeveral groups and resources provide information that pertains to the validity of gene-disease relationships used in genomic medicine and research; however, universal standards and terminologies to define the evidence base for the role of a gene in disease, and a single harmonized resource were lacking. To tackle this issue, the Gene Curation Coalition (GenCC) was formed.METHODSThe GenCC drafted harmonized definitions for differing levels of gene-disease validity based on existing resources, and performed a modified Delphi survey with three rounds to narrow the list of terms. The GenCC also developed a unified database to display curated gene-disease validity assertions from its members.RESULTSBased on 241 survey responses from the genetics community, a consensus term set was chosen for grading gene-disease validity and database submissions. As of December 2021, the database contains 15,241 gene-disease assertions on 4,569 unique genes from 12 submitters. When comparing submissions to the database from distinct sources, conflicts in assertions of gene-disease validity ranged from 5.3% to 13.4%.CONCLUSIONTerminology standardization, sharing of gene-disease validity classifications, and resolution of curation conflicts will facilitate collaborations across international curation efforts and in turn, improve consistency in genetic testing and variant interpretation.
Rare schizophrenia risk variant burden is conserved in diverse human populations
Authors: Liu Dongjing , Meyer Dara , Fennessy Brian , Feng Claudia , Cheng Esther , Johnson Jessica S. , Park You Jeong , Rieder Marysia-Kolbe , Ascolillo Steven , de Pins Agathe , Dobbyn Amanda , Lebovitch Dannielle , Moya Emily , Nguyen Tan-Hoang , Wilkins Lillian , Hassan Arsalan ,   Psychiatric Genomics Consortium Phase 3 Targeted Sequencing of Schizophrenia Study Team,   Schizophrenia Exome Meta-analysis Consortium, Burdick Katherine E. , Buxbaum Joseph D. , Domenici Enrico , Frangou Sophia , Hartmann Annette M. , Malhotra Dheeraj , Pato Carlos N. , Pato Michele T. , Ressler Kerry , Roussos Panos , Rujescu Dan , Arango Celso , Bertolino Alessandro , Blasi Giuseppe , Bocchio-Chiavetto Luisella , Campion Dominique , Carr Vaughan , Fullerton Janice M. , Gennarelli Massimo , González-Peñas Javier , Levinson Douglas F. , Mowry Bryan , Nimgaokar Vishwajit L. , Pergola Giulio , Rampino Antonio , Rivera-Sanchez Margarita , Schwab Sibylle G. , Wildenauer Dieter B. , Daly Mark , Neale Benjamin , Singh Tarjinder , O’Donovan Michael C. , Owen Michael J. , Walters James T. , Ayub Muhammad , Malhotra Anil K. , Lencz Todd , Sullivan Patrick F. , Sklar Pamela , Stahl Eli A. , Huckins Laura M. , Charney Alexander W. 
Published: January 2022

AbstractSchizophrenia is a chronic mental illness that is amongst the most debilitating conditions encountered in medical practice. A recent landmark schizophrenia study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This study -- and most other large-scale human genetic studies -- was mainly composed of individuals of European ancestry, and the generalizability of the findings in non-European populations is unclear. To address this gap in knowledge, we designed a custom sequencing panel based on current knowledge of the genetic architecture of schizophrenia and applied it to a new cohort of 22,135 individuals of diverse ancestries. Replicating earlier work, cases carried a significantly higher burden of rare protein-truncating variants among constrained genes (OR=1.48, p-value = 5.4 × 10−6). In meta-analyses with existing schizophrenia datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five continental populations. Two genes (SRRM2andAKAP11) were newly implicated as schizophrenia risk genes, and one gene (PCLO) was identified as a shared risk gene for schizophrenia and autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of schizophrenia being conserved across diverse human populations.
Immunological Cross-Reactivity to Dengue Virus among Persons with Neuroinvasive West Nile Virus Infection
Authors: Raabe Vanessa , Natrajan Muktha S. , Huerta Chris , Xu Yongxian , Lai Lilin , Mulligan Mark J. 
Published: January 2022

AbstractAntibody dependent enhancement has been well described between Zika and dengue viruses, but is poorly characterized between West Nile and dengue viruses. We demonstrate that neuroinvasive West Nile virus infection leads to the development of non-neutralizing, cross-reactive IgG antibodies to dengue and Zika viruses capable of causing antibody dependent enhancement in vitro of dengue virus and leads to the formation of flavivirus cross-reactive memory B cells in some patients.
Explaining the microbial diversity conundrum: can microbiome composition be crucial for host fitness, while highly divergent among healthy individuals?
Authors: Daybog Itay , Kolodny Oren 
Published: January 2022

AbstractRecent empirical studies offer conflicting findings regarding the relation between host fitness and the composition of its microbiome, a conflict which we term themicrobial β - diversity conundrum: it has been shown that the microbiome is crucial for host wellbeing and survival. At the same time, different healthy individuals’ microbiome compositions, even in the same population, often differ dramatically, contrary to the notion that a vital trait should be highly conserved. Moreover, gnotobiotic individuals exhibit highly deleterious phenotypes, supporting the notion that the microbiome is paramount to host fitness. However, the introduction of almost arbitrarily selected microbiota into the system often achieves a significant rescue effect of the deleterious phenotypes, even microbiota from soil or phylogenetically distant host species, highlighting an apparent paradox. Here we suggest several solutions to the paradox using a computational framework, simulating the population dynamics of hosts and their microbiomes over multiple generations. The answers, relating to factors such as host population size, the specific mode of contribution of the microbes to host fitness, and the typical microbiome richness, offer solutions to the conundrum by creating scenarios where even when a host’s fitness is determined in full by its microbiome composition, this composition has little or no effect on the natural selection dynamics of the population.
Omicron variant escapes therapeutic mAbs contrary to eight prior main VOC
Authors: Boschi Céline , Colson Philippe , Bancod Audrey , Moal Valérie , Scola Bernard La 
Published: January 2022

AbstractMonocolonal antibodies (mAbs) are currently used for active immunization of COVID-19 in immunocompromised patients. We herein show that in spite there are variations in susceptibility to available mAbs that are authorized for clinical use in France tested on the original B.1.1 virus and 9 variants of concern or of interest, the cocktail casirivimab/imdevimab (REGN-CoV-2) showed a major synergistic effect. However, none of the four mAbs either alone or in combination neutralized the new Omicron variant. Our data strongly warrant a reinforcement of protective measures against infection for immunocompromised patients.
Phylogeographic analysis reveals an ancient East African origin of the human herpes simplexvirus 2 dispersal out-of-Africa
Authors: Havens Jennifer L. , Calvignac-Spencer Sébastien , Merkel Kevin , Burrel Sonia , Boutolleau David , Wertheim Joel O. 
Published: January 2022

AbstractHuman herpes simplex virus 2 (HSV-2) is a globally ubiquitous, slow evolving DNA virus. HSV-2 genomic diversity can be divided into two main groups: an African lineage and worldwide lineage. Competing hypotheses have been put forth to explain the history of HSV-2. HSV-2 may have originated in Africa and then followed the first wave of human migration out of Africa between 50-100 kya. Alternatively, HSV-2 may have migrated out of Africa via the trans-Atlantic slave trade within the last 150-500 years. The lack of HSV-2 genomes from West and Central Africa, combined with a lack of molecular clock signal in HSV-2 has precluded robust testing of these competing hypotheses. Here, we expand the geographic sampling of HSV-2 genomes in order to resolve the geography and timing of divergence events within HSV-2. We analyze 65 newly sequenced HSV-2 genomes collected from primarily West and Central Africa along with 330 previously published genomes sampled over a 47-year period. Evolutionary simulations confirm that the molecular clock in HSV-2 is too slow to be detected using available data. However, phylogeographic analysis indicates that all biologically plausible evolutionary rates would place the ancestor of the worldwide lineage in East Africa, arguing against the trans-Atlantic slave trade as the source of worldwide diversity. The best supported evolutionary rates between 4.2×10−8 and 5.6×10−8 substitutions/site/year suggest a most recent common ancestor for HSV-2 around 90-120 kya and initial dispersal around 21.9-29.3 kya. These dates suggest HSV-2 left Africa during subsequent waves of human migration out of East Africa.