bluuebunny/crossref_metadata_2025_split huggingface dataset:
Considerations regarding a diagnosis of Alzheimer’s Disease before dementia: a systematic review
Authors: van der Schaar Jetske , Visser Leonie N.C. , Bouwman Femke H. , Scheltens Philip , Bredenoord Annelien L. , van der Flier Wiesje M. 
Published: September 2021

ABSTRACTIntroductionThe NIA-AA research framework proposes a purely biological definition of Alzheimer’s Disease (AD). This implies AD can be diagnosed based on biomarker abnormalities. While this brings opportunities, it also raises challenges.MethodsWe conducted a systematic review by searching PubMed for publications on conveying AD biomarker results to individuals without dementia. Content was analyzed inductively.ResultsWe included 25 publications. From these we extracted 26 considerations, which we grouped according to their primary relevance to a clinical, personal, or societal context. Clinical considerations include (lack of) validity, utility, and disclosure protocols. Personal considerations cover psychological and behavioral implications, as well as the right to (not) know. Societal considerations comprise the risk of misconception, stigmatization, and discrimination. Overall, views were heterogeneous and often contradictory.DiscussionPerceptions on a diagnosis of AD before dementia vary widely. Empirical research is required, taking perspectives of medical professionals and the general public into account.
Dichotomy between the humoral and cellular responses elicited by mRNA and adenoviral vector vaccines against SARS-CoV-2
Authors: Ukey Rahul , Bruiners Natalie , Mishra Hridesh , Mishra Pankaj K. , McCloskey Deborah , Onyuka Alberta , Chen Fei , Pinter Abraham , Weiskopf Daniela , Sette Alessandro , Roy Jason , Gaur Sunanda , Gennaro Maria Laura 
Published: September 2021

AbstractProtection from severe disease and hospitalization by SARS-CoV-2 vaccination has been amply demonstrated by real-world data. However, the rapidly evolving pandemic raises new concerns. One pertains efficacy of adenoviral vector-based vaccines, particularly the single-dose Ad26.COV2.S, relative to mRNA vaccines. We investigated the immunogenicity of Ad26.COV2.S and mRNA vaccines in 33 subjects vaccinated with either vaccine class five months earlier on average. After controlling for time since vaccination, Spike-binding antibody and neutralizing antibody levels were higher in the mRNA-vaccinated subjects, while no significant differences in antigen-specific B cell and T cell responses were observed between the two groups. Thus, a dichotomy exists between humoral and cellular responses elicited by the two vaccine classes. Our results have implications for the need of booster doses in vaccinated subjects and might explain the dichotomy reported between the waning protection from symptomatic infection by SARS-CoV-2 vaccination and its persisting efficacy in preventing hospitalization and death.
Acetobase: database update and reanalysis of formyltetrahydrofolate synthetase amplicon sequencing data from the anaerobic digesters
Authors: Singh Abhijeet , Schnürer Anna 
Published: September 2021

ABSTRACTAcetoBase is a public repository and database published in 2019, for the formyltetrahydrofolate synthetase (FTHFS) sequences. It is the first systematic collection of bacterial formyltetrahydrofolate nucleotide and protein sequences from the genomes and metagenome assembled genomes (MAGs), as well as sequences generated by clone library sequencing. In addition, AcetoBase was first to establish connection between FTHFS gene with the Wood-Ljungdahl pathway and 16S rRNA genes. Since the publication of AcetoBase, significant improvements were seen in the taxonomy of many bacterial lineages and accessibility/availability of public genomics and metagenomics data. Thus, an update to the AcetoBase database with new sequence data and taxonomy has been made along with improvements in web-functionality and user interface. The update in AcetoBase reference database version 2 was furthermore evaluated by reanalysis of publicly accessible FTHFS amplicon sequencing data previously analysed with AcetoBase version 1. The latest database update showed significant improvements in the taxonomic assignments of FTHFS sequences. AcetoBase with its enhancements in functionality and content is publicly accessible at https://acetobase.molbio.slu.se.
Unsupervised mining of HLA-I peptidomes reveals new binding motifs and substantial false positives in community database
Authors: Sricharoensuk Chatchapon , Boonchalermvichien Tanupat , Muanwien Phijitra , Somparn Poorichaya , Pisitkun Trairak , Sriswasdi Sira 
Published: September 2021

AbstractModern vaccine designs and studies of human leukocyte antigen (HLA)-mediated immune responses rely heavily on the knowledge of HLA allele-specific binding motifs and computational prediction of HLA-peptide binding affinity. Breakthroughs in HLA peptidomics have considerably expanded the databases of natural HLA ligands and enabled detailed characterizations of HLA-peptide binding specificity. However, cautions must be made when analyzing HLA peptidomics data because identified peptides may be contaminants in mass spectrometry or may weakly bind to the HLA molecules. Here, a hybridde novopeptide sequencing approach was applied to large-scale mono-allelic HLA peptidomics datasets to uncover new ligands and refine current knowledge of HLA binding motifs. Up to 12-40% of the peptidomics data were low-binding affinity peptides with an arginine or a lysine at the C-terminus and likely to be tryptic peptide contaminants. Thousands of these peptides have been reported in a community database as legitimate ligands and might be erroneously used for training prediction models. Furthermore, unsupervised clustering of identified ligands revealed additional binding motifs for several HLA class I alleles and effectively isolated outliers that were experimentally confirmed to be false positives. Overall, our findings expanded the knowledge of HLA binding specificity and advocated for more rigorous interpretation of HLA peptidomics data that will ensure the high validity of community HLA ligandome databases.
Body fat volumes and distribution in chronic schizophrenia compared to healthy controls; a cross-sectional MR study
Authors: Osimo Emanuele F. , Brugger Stefan P. , Thomas E. Louise , Howes Oliver D. 
Published: September 2021

SummaryPeople with schizophrenia show higher risk for abdominal obesity than the general population, which could contribute to excess mortality. However, it is unclear whether this is driven by alterations in abdominal fat partitioning. Here, we test the hypothesis that individuals with schizophrenia show a higher proportion of visceral to total body fat measured using MRI. We recruited 38 patients with schizophrenia and 38 healthy controls matched on age, sex, ethnicity and body mass index. We found no significant difference in body fat distribution between groups, suggesting that increased abdominal obesity in schizophrenia is not associated with altered fat distribution.
Psychedelic mushrooms in the USA: Knowledge, patterns of use and association with health outcomes
Authors: Matzopoulos R , Morlock R , Morlock A , Lerer B , Lerer L 
Published: September 2021

ABSTRACTIntroductionPopular media coverage, including of recent positive late stage clinical trials in depression and PTSD, and decriminalization initiatives, are transforming the public perception of psychedelics. However, little is known about levels of knowledge and personal use of psychedelic mushroom(s) (PM) among American adults.MethodsWe examined PM use and various measures of health status, quality of life and self-reported mental health outcome measures obtained through a national on-line, cross-sectional survey of adults with a demographic composition representative of the US adult population by region, gender, age, and race (weighted N = 251,297,495) from November 2020–March 2021.ResultsGeneral mental health and well-being was a popular reason for PM use (63.6%). PM users were less likely to be overweight than non-users, but overall quality of life (VR-12) was lower for mental health (39.5 vs 45.5). PM users reported significantly higher levels of anxiety (GAD-7 scores of 9.6 vs 5.9) and depression (PHQ-9 scores of 11.2 vs 6.8). They were less likely to have health insurance [OR=0.50 (0.35-0.72)], but reported significantly more healthcare services utilization.Discussion and ConclusionsThere is a mismatch between our findings of an association between PM use and poor mental health outcomes, and current discourse on the positive health benefits of PM consumption. A significant number of Americans are already “self medicating” with PM and further research to understand the role of anecdotal knowledge and pseudoscientific information in PM uptake. There is an urgent need for a PM use-related national harm reduction strategy.
Retinal oxygen delivery and extraction in ophthalmologically healthy subjects with different blood pressure status
Authors: Pappelis Konstantinos , Jansonius Nomdo M. 
Published: September 2021

AbstractPurposeTo compare retinal oxygen delivery (DO2) and extraction (VO2) in ophthalmologically healthy subjects with different blood pressure (BP) status.MethodsIn this case-control study, we prospectively included 93 eyes of 93 subjects (age 50-65) from a large-scale population-based Dutch cohort (n=167,000) and allocated them to four groups (low BP, normal BP [controls], treated arterial hypertension [AHT], untreated AHT). We estimated vascular calibers from fundus images and fractal dimension (FD) from optical coherence tomography angiography scans. We combined calibers, FD, BP, and intraocular pressure measurements in a proxy of total retinal blood flow (RBF), using a validated Poiseuille-based model. We measured arterial and venous oxygen saturations (SaO2, SvO2) with a two-wavelength scanning laser ophthalmoscope. We calculated DO2 and VO2 from RBF, SaO2, and SvO2. We compared DO2 and VO2 between groups and investigated the DO2-VO2 association.ResultsDO2 and VO2 were different between groups (P=0.009, P=0.036, respectively). In post hoc analysis, the low BP group had lower DO2 than the untreated AHT group (P=4.9·10-4), while both the low BP group and the treated AHT group had lower VO2 than the untreated AHT group (P=0.021, P=0.034, respectively). There was a significant DO2-VO2 correlation (Robs=0.65, bobs=0.51, P=2.4·10-12). After correcting for shared measurement error, the slope was no longer significant (bcor=0.19, P=0.29), while the correlation coefficient could not be calculated.ConclusionsDO2 and VO2 were altered in ophthalmologically healthy subjects with different BP status. Future studies could elucidate whether these changes can explain the increased risk of several ophthalmic pathologies in those subjects.
Vitamin D and socioeconomic deprivation mediate COVID-19 ethnic health disparities
Authors: Mariño-Ramírez Leonardo , Ahmad Maria , Rishishwar Lavanya , Nagar Shashwat Deepali , Lee Kara K. , Norris Emily T. , Jordan I. King 
Published: September 2021

AbstractEthnic minorities in developed countries suffer a disproportionately high burden of COVID-19 morbidity and mortality, and COVID-19 ethnic disparities have been attributed to social determinants of health. Vitamin D has been proposed as a modifiable risk factor that could mitigate COVID-19 health disparities. We investigated the relationship between vitamin D and COVID-19 susceptibility and severity using the UK Biobank, a large progressive cohort study of the United Kingdom population. Structural equation modelling was used to evaluate the ability of vitamin D, socioeconomic deprivation, and other known risk factors to mediate COVID-19 ethnic health disparities. Asian ethnicity is associated with higher COVID-19 susceptibility, compared to the majority White population, and Asian and Black ethnicity are both associated with higher COVID-19 severity. Socioeconomic deprivation mediates all three ethnic disparities and shows the highest overall signal of mediation for any COVID-19 risk factor. Vitamin supplements, including vitamin D, mediate the Asian disparity in COVID-19 susceptibility, and serum 25-hydroxyvitamin D (calcifediol) levels mediate Asian and Black COVID-19 severity disparities. Several measures of overall health also mediate COVID-19 ethnic disparities, underscoring the importance of comorbidities. Our results support ethnic minorities’ use of vitamin D as both a prophylactic and a supplemental therapeutic for COVID-19.
Surgical Resection, Radiotherapy, And Percutaneous Thermal Ablation for Treatment of Stage 1 Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis
Authors: Chockalingam Arun , Koo Brandon , Moon John T. , Konstantinidis Menelaos , Tran Andrew , Nourouzpour Sahar , Lawson Emily , Fox Kathleen , Habibollahi Peiman , Odisio Bruno C. , Loya Mohammed , Bassir Ali , Nezami Nariman 
Published: September 2021

ABSTRACTIntroductionNon-small cell lung cancer (NSCLC) makes up the majority of lung cancer cases. Currently surgical resection of the affected lung parenchyma is the gold standard of treatment. However, as patients are becoming medically more complex and presenting with more advanced disease, minimally invasive image guided percutaneous ablations are gaining popularity. Therefore, comparison of surgical, ablative, and second-line external beam therapies will help clinicians, as management of NSCLC changes. We will conduct a meta-analysis, reviewing literature investigating these therapies in adult patients diagnosed with Stage I NSCLC (tumor ranging from 0-5 cm, with no hilar nor mediastinal nodal involvement, confirmed either through cytology or histology regardless of type).Methods and AnalysisWe will search electronic databases from their inception to January 2021 to identify randomized controlled trials (RCTs), cluster-RCTs, and cohort studies comparing the survival and clinical outcomes between any two interventions (lobectomy, wedge resection, radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation and consolidated radiation therapies (EBRT, SBRT and 3D-CRT). The primary outcomes will include: cancer-specific survival (CSS), lung disease free survival, locoregional recurrence, death, toxicity, and non-target organ injury. In addition to the electronic databases, we will search for published and unpublished studies in trial registries and will review the references of included studies for possible inclusion in this review. Risk of bias will be assess using tools developed by the Cochrane collaboration. Two reviewers will independently assess the eligibility of studies and conduct the corresponding risk-of-bias assessments. For each outcome, given a sufficient number of studies, we will conduct a network meta-analysis. Finally, we will use the Confidence in Network meta-analysis (CINeMA) tool to assess the quality of the evidence for each of the primary outcomes.Ethics and DisseminationWe aim to share our findings through high-impact peer review. As interventional techniques become more popular, it will be important for all providers in multi-disciplinary teams focused on care of these patients to receive continuing medical education on related to these interventions. Data synthesized in this study will be made available to readers.
YfiB: An Outer Membrane Protein Involved in the Virulence of Shigella flexneri
Authors: Sen Tanuka , Verma Naresh K 
Published: September 2021

ABSTRACTThe intracellular pathogen Shigella flexneri, which is the causative agent of bacillary dysentery, significantly influences the worldwide implication of diarrheal infections, consequentially causing about 1.1 million deaths each year. Due to a non-availability of an authorized vaccine and the upsurge of multidrug resistance amongst Shigella strains, there has been a huge demand for further genetic analyses which could help in the advancement of new/improved drugs, and finding vaccine candidates against the pathogen. Whilst many features about the invasion of colonic cells by Shigella have been identified, fundamental gaps in information concerning in what way the bacteria transit, survive, and control gene expression, remain. The present study aims to illustrate the role of yfiB gene in Shigella virulence, which is a part of the periplasmic YfiBNR tripartite signaling system. This system is involved in the regulation of cyclic-di-GMP levels inside the bacterial cells, which is a vital messenger molecule impacting varied cellular processes such as biofilm formation, cytotoxicity, motility, synthesis of exopolysaccharide, and other virulence mechanisms like adhesion and invasion of the bacteria. Through a combination of genetic, biochemical, and virulence assays, we show how knocking out the yfiB gene can disrupt the entire YfiBNR system and affect biofilm formation, bacterial invasion, host-surface attachment, and the overall virulence of Shigella. This study eventually improves our understanding of the in-vivo persistence and survival of Shigella, brings light to the c-di-GMP lead regulation of Shigella virulence, and provides a prospective new target to design anti-infective drugs and vaccines against S. flexneri and other bacterial pathogens.
Probing differences in gene essentiality between the human and animal adapted lineages of the Mycobacterium tuberculosis complex using TnSeq
Authors: Gibson Amanda J , Passmore Ian J , Faulkner Valwynne , Xia Dong , Nobeli Irene , Stiens Jennifer , Willcocks Sam , Werling Dirk , Villarreal-Ramos Bernardo , Wren Brendan W , Kendall Sharon L 
Published: September 2021

AbstractMembers of the Mycobacterium tuberculosis complex (MTBC) show distinct host adaptations, preferences and phenotypes despite being >99% identical at the nucleic acid level. Previous studies have explored gene expression changes between the members, however few studies have probed differences in gene essentiality. To better understand the functional impacts of the nucleic acid differences between Mycobacterium bovis and Mycobacterium tuberculosis we used the Mycomar T7 phagemid delivery system to generate whole genome transposon libraries in laboratory strains of both species and compared the essentiality status of genes during growth under identical in vitro conditions. Libraries contained insertions in 54% of possible TA sites in M. bovis and 40% of those present in M. tuberculosis, achieving similar saturation levels to those previously reported for the MTBC. The distributions of essentiality across the functional categories were similar in both species. 527 genes were found to be essential in M. bovis whereas 477 genes were essential in M. tuberculosis and 370 essential genes were common in both species. CRISPRi was successfully utilised in both species to determine the impacts of silencing genes including wag31, a gene involved in peptidoglycan synthesis and Rv2182c/Mb2204c, a gene involved in glycerophospholipid metabolism. We observed species specific differences in the response to gene silencing, with the inhibition of expression of Mb2204c in M. bovis showing significantly less growth impact than silencing its ortholog (Rv2182c) in M. tuberculosis. Given that glycerophospholipid metabolism is a validated pathway for antimicrobials, our observations suggest that target vulnerability in the animal adapted lineages cannot be assumed to be the same as the human counterpart. This is of relevance for zoonotic tuberculosis as it implies that the development of antimicrobials targeting the human adapted lineage might not necessarily be effective against the animal adapted lineage. The generation of a transposon library and the first reported utilisation of CRISPRi in M. bovis will enable the use of these tools to further probe the genetic basis of survival under disease relevant conditions.
Zika virus causes placental pyroptosis and associated adverse fetal outcomes by activating GSDME
Authors: Zhao Zikai , Li Qi , Ashraf Usama , Yang Mengjie , Zhu Wenjing , Chen Zheng , Cao Shengbo , Ye Jing 
Published: September 2021

AbstractZika virus (ZIKV) can be transmitted from mother to fetus during pregnancy, causing adverse fetal outcomes. Several studies have indicated that ZIKV can damage the fetal brain directly; however, whether the ZIKV-induced maternal placental injury contribute to adverse fetal outcomes are sparsely defined. Here, we discovered that ZIKV causes the pyroptosis of placental cells by activating the executor Gasdermin E (GSDME) in vitro and in vivo. Mechanistically, caspase-8 undergoes activation upon the recognition of 5’ untranslated region of viral RNA by RIG-I, followed by the stimulation of caspase-3 to ultimately escalate the GSDME cleavage. Further analyses revealed that the ablation of GSDME in ZIKV-infected pregnant mice attenuates placental pyroptosis, which consequently confers protection against adverse fetal outcomes. In conclusion, our study unveils a novel mechanism of ZIKV-induced adverse fetal outcomes via causing placental cell pyroptosis, which could be employed for developing new therapies for ZIKV-associated diseases.Significance statementSeveral studies have elucidated the link between ZIKV infection and congenital ZIKV syndroms (CZS), but the pathogenesis yet needs further study. Here, we reported a novel pathogenic mechanism of ZIKV which leads to pyroptosis of placental cells through activating the pyroptotic executor GSDME, rather than GSDMD. Upon ZIKV infection, GSDME-mediated pyroptosis damages the structure and function of the placenta, thereby affecting the development of the fetus and contributing to the adverse fetal outcomes. Our study highlights the importance of pyroptotic executor GSDME in regulate ZIKV pathogenicity and further confirms that placental injury caused by ZIKV infection is a key factor for CZS.
Hematopoietic recovery after transplantation is primarily derived from the stochastic contribution of hematopoietic stem cells
Authors: Radtke Stefan , Enstrom Mark , Pande Dnyanada , Cui Margaret , Madhu Ravishankar , Perez Anai M. , Kiem Hans-Peter 
Published: September 2021

ABSTRACTReconstitution after hematopoietic stem cell (HSC) transplantation is assumed to occur in two distinct phases: initial recovery mediated by short-term progenitors and long-term repopulation by multipotent HSCs which do not contribute to hematopoietic reconstitution during the first 6-9 months. We have previously reported the transplantation and exclusive engraftment of the HSC-enriched CD34+CD45RA-CD90+ phenotype in a nonhuman primate model. Here, we closely followed the clonal diversity and kinetics in these animals. Enhanced sampling and high density clonal tracking within the first 3 month revealed that multipotent HSCs actively contributed to the early phases of neutrophil recovery and became the dominant source for blood cells as early as 50 days after transplant. Longitudinal changes in clonal diversity supported a stochastic engraftment of HSCs with the majority of HSCs clones vanishing early during neutrophil recovery and a smaller fraction of HSC clones expanding into bigger pools to support long-term hematopoiesis. In contrast to the bi-phasic model, we propose that hematopoietic recovery after myeloablation and transplantation is primarily derived from HSCs in a stochastic manner rather than in two phases by independent cell populations.