bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality disparities among patients with HIV-associated Kaposi's sarcoma in the southern United States
Authors: Knights Sheena M. , Lazarte Susana M. , Kainthla Radhika , Chiao Elizabeth Y. , Nijhawan Ank E. 
Published: December 2021

Objective:
To describe risk factors for mortality in HIV-associated Kaposi's sarcoma in an urban population in Dallas, Texas.

Design:
Retrospective electronic medical record review of patients with HIV-associated Kaposi's sarcoma.

Methods:
Electronic medical records were reviewed from 1 January 2009 to 31 December 2018 for patients with a diagnosis of HIV and Kaposi's sarcoma by ICD-9 or ICD-10 codes. Demographics, HIV history, Kaposi's sarcoma history, treatment, and mortality data were collected. Mortality data was supplemented by an inquiry from the National Death Index (NDI). Survival analyses were performed using Cox proportional hazards analysis to determine independent predictors of mortality.

Results:
Black patients had higher mortality than white or Hispanic patients (hazard ratio 2.07, 95% confidence interval 1.12–3.82), even after adjusting for covariates. This mortality difference correlates with higher rates of advanced Kaposi's sarcoma disease and KS-IRIS in black patients compared with other groups and is not explained by differences in CD4+ cell count, HIV viral load, engagement in care, or ART adherence at the time of cancer diagnosis.

Conclusion:
Despite nationwide trends showing decreased incidence and decreased mortality in Kaposi's sarcoma in the ART era, a high number of Kaposi's sarcoma cases and disparities in Kaposi's sarcoma outcomes persist in certain populations in the United States.
Impact of COVID-19 on care of older adults with cancer: a narrative synthesis of reviews, guidelines and recommendations
Authors: Haase Kristen R. , Verma Ridhi , Kilgour Heather M. 
Published: December 2021

Purpose of review
The aim of this study was to summarize the literature on the impact of COVID-19 on older adults with cancer, including both the impacts of COVID-19 diagnosis on older adults with cancer and the implications of the pandemic on cancer care via a synthesis of reviews, guidelines and other relevant literature.

Recent findings
Our synthesis of systematic reviews demonstrates that older adults with cancer are prone to greater morbidity and mortality when experiencing concurrent COVID-19 infection. Current evidence related to the association between anticancer treatment and COVID-19 prognosis for older adults with cancer is conflicting. Guidelines and recommendations advocate for preventive measures against COVID-19; the uptake of telemedicine and virtual care; encourage vaccination for older adults with cancer; and the use of geriatric assessment.

Summary
The COVID-19 virus itself may be particularly deleterious for older adults with cancer. However, the health system and social impact of the pandemic, including global disruptions to the healthcare system and related impacts to the delivery of cancer care services, have equally important consequences.
Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma
Authors: Sullivan David J. , Gebo Kelly A. , Shoham Shmuel , Bloch Evan M. , Lau Bryan , Shenoy Aarthi G. , Mosnaim Giselle S. , Gniadek Thomas J. , Fukuta Yuriko , Patel Bela , Heath Sonya L. , Levine Adam C. , Meisenberg Barry R. , Spivak Emily S. , Anjan Shweta , Huaman Moises A. , Blair Janis E. , Currier Judith S. , Paxton James H. , Gerber Jonathan M. , Petrini Joann R. , Broderick Patrick B. , Rausch William , Cordisco Marie Elena , Hammel Jean , Greenblatt Benjamin , Cluzet Valerie C. , Cruser Daniel , Oei Kevin , Abinante Matthew , Hammitt Laura L. , Sutcliffe Catherine G. , Forthal Donald N. , Zand Martin S. , Cachay Edward R. , Raval Jay S. , Kassaye Seble G. , Foster E. Colin , Roth Michael , Marshall Christi E. , Yarava Anusha , Lane Karen , McBee Nichol A. , Gawad Amy L. , Karlen Nicky , Singh Atika , Ford Daniel E. , Jabs Douglas A. , Appel Lawrence J. , Shade David M. , Ehrhardt Stephan , Baksh Sheriza N. , Laeyendecker Oliver , Pekosz Andrew , Klein Sabra L. , Casadevall Arturo , Tobian Aaron A.R. , Hanley Daniel F. 
Published: December 2021

ABSTRACTBACKGROUNDThe efficacy of polyclonal high titer convalescent plasma to prevent serious complications of COVID-19 in outpatients with recent onset of illness is uncertain.METHODSThis multicenter, double-blind randomized controlled trial compared the efficacy and safety of SARS-CoV-2 high titer convalescent plasma to placebo control plasma in symptomatic adults ≥18 years positive for SARS-CoV-2 regardless of risk factors for disease progression or vaccine status. Participants with symptom onset within 8 days were enrolled, then transfused within the subsequent day. The measured primary outcome was COVID-19-related hospitalization within 28 days of plasma transfusion. The enrollment period was June 3, 2020 to October 1, 2021.RESULTSA total of 1225 participants were randomized and 1181 transfused. In the pre-specified modified intention-to-treat analysis that excluded those not transfused, the primary endpoint occurred in 37 of 589 (6.3%) who received placebo control plasma and in 17 of 592 (2.9%) participants who received convalescent plasma (relative risk, 0.46; one-sided 95% upper bound confidence interval 0.733; P=0.004) corresponding to a 54% risk reduction. Examination with a model adjusting for covariates related to the outcome did not change the conclusions.CONCLUSIONEarly administration of high titer SARS-CoV-2 convalescent plasma reduced outpatient hospitalizations by more than 50%. High titer convalescent plasma is an effective early outpatient COVID-19 treatment with the advantages of low cost, wide availability, and rapid resilience to variant emergence from viral genetic drift in the face of a changing pandemic.Trial RegistrationClinicalTrials.gov number, NCT04373460.
Possible Cross Reactivity of Feline and White-tailed Deer Antibodies Against the SARS-CoV-2 Receptor Binding Domain
Authors: Hancock Trevor J. , Hickman Peyton , Kazerooni Niloo , Kennedy Melissa , Kania Stephen A. , Dennis Michelle , Szafranski Nicole , Gerhold Richard , Su Chunlei , Masi Tom , Smith Stephen , Sparer Tim E. 
Published: December 2021

AbstractIn late 2019, a novel coronavirus began circulating within humans in central China. It was designated SARS-CoV-2 because of its genetic similarities to the 2003 SARS coronavirus (SARS-CoV). Now that SARS-CoV-2 has spread worldwide, there is a risk of it establishing new animal reservoirs and recombination with native circulating coronaviruses. To screen local animal populations in the United States for exposure to SARS-like coronaviruses, we developed a serological assay using the receptor binding domain (RBD) from SARS-CoV-2. SARS-CoV-2’s RBD is antigenically distinct from common human and animal coronaviruses allowing us to identify animals previously infected with SARS-CoV or SARS-CoV-2. Using an indirect ELISA for SARS-CoV-2’s RBD, we screened serum from wild and domestic animals for the presence of antibodies against SARS-CoV-2’s RBD. Surprisingly pre-pandemic feline serum samples submitted to the University of Tennessee Veterinary Hospital were ∼50% positive for anti-SARS RBD antibodies. Some of these samples were serologically negative for feline coronavirus (FCoV), raising the question of the etiological agent generating anti-SARS-CoV-2 RBD cross-reactivity. We also identified several white-tailed deer from South Carolina with anti-SARS-CoV-2 antibodies. These results are intriguing as cross-reactive antibodies towards SARS-CoV-2 RBD have not been reported to date. The etiological agent responsible for seropositivity was not readily apparent, but finding seropositive cats prior to the current SARS-CoV-2 pandemic highlights our lack of information about circulating coronaviruses in other species.ImportanceWe report cross-reactive antibodies from pre-pandemic cats and post-pandemic South Carolina white-tailed deer that are specific for that SARS-CoV RBD. There are several potential explanations for this cross-reactivity, each with important implications to coronavirus disease surveillance. Perhaps the most intriguing possibility is the existence and transmission of an etiological agent (such as another coronavirus) with similarity to SARS-CoV-2’s RBD region. However, we lack conclusive evidence of pre-pandemic transmission of a SARS-like virus. Our findings provide impetus for the adoption of a One Health Initiative focusing on infectious disease surveillance of multiple animal species to predict the next zoonotic transmission to humans and future pandemics.
A Meta-Analysis of the 16S-rRNA Gut Microbiome Data in Honeybees (Apis Mellifera)
Authors: Gkantiragas Alexis G. , Gabrielli Jacopo 
Published: December 2021

1.AbstractHoneybees (Apis Mellifera) perform an essential role in the ecosystem and economy through pollination of insect-pollinated plants, but their population is declining. Many causes of honeybees’ decline are likely to be influenced by the microbiome which is thought to play an important role in bees and is particularly susceptible to infection and pesticides. However, there has been no systematic review or meta-analysis on honeybee microbiome data. Therefore, we conducted the first systematic meta-analysis of 16S-rRNA data to address this gap in the literature. Four studies were in a usable format – accounting for 336 honeybee’s worth of data – the largest such dataset to the best of our knowledge. We analysed these datasets in QIIME2 and visualised the results in R-studio. For the first time, we conducted a multi-study evaluation of the core and rare bee microbiome and confirmed previous compositional microbiome data. We established that Snodgrassella, Lactobacillus, Bifidobacterium, Fructobacillus and Saccaribacter form part of the core microbiome and identify 251 rare bacterial genera. Additional components of the core microbiome were likely obscured by incomplete classification. Future studies should refine and add to our existing dataset to produce a more conclusive and high-resolution portrait of the honeybee microbiome. Furthermore, we emphasise the need for an actively curated dataset and enforcement of data sharing standards.Abstract FigureFigure 1Graphical abstract.Made by the author in Biorender.com.
Superior immunogenicity and effectiveness of the 3rd BNT162b2 vaccine dose
Authors: Lustig Yaniv , Gonen Tal , Melzer Lilac , Gilboa Mayan , Indenbaum Victoria , Cohen Carmit , Amit Sharon , Jaber Hanaa , Doolman Ram , Asraf Keren , Rubin Carmit , Fluss Ronen , Mendelson Ella , Freedman Laurence , Regev-Yochay Gili , Kreiss Yitshak 
Published: December 2021

AbstractIn a prospective cohort study involving 12,413 Health Care Workers (HCW), we assessed immunogenicity, vaccine-effectiveness (VE) and safety of the third BNT162b2 vaccine dose. One month after third dose, anti-RBD-IgG were induced 1.7-folds compared to one month after the second. A significant increase in avidity from 61.1% (95%CI:56.1-66.7) to 96.3% (95%CI:94.2-98.5) resulted in a 6.1-folds neutralizing antibodies induction. Linear mixed model demonstrated that the third dose elicited a greater response among HCW≥60 or those with ≥two comorbidities who had a lower response following the second dose. VE of the third dose relative to two doses was 85.6% (95% CI, 79.2-90.1%). No serious adverse effects were reported. These results suggest that the third dose is superior to the second dose in both quantity and quality of IgG-antibodies and safely boosts protection from SARS-CoV-2 infection by generating high avidity antibodies to levels that are not significantly different between healthy and vulnerable populations.
Eukaryotic translation initiation factor eIF4E-5 is required for spermiogenesis in Drosophila melanogaster
Authors: Shao Lisa , Fingerhut Jaclyn M. , Falk Brook L. , Han Hong , Maldonado Giovanna , Qiao Yuemeng , Lee Vincent , Hall Elizabeth , Chen Liang , Polevoy Gordon , Hernández Greco , Lasko Paul , Brill Julie A. 
Published: December 2021

AbstractDrosophila sperm development is characterized by extensive post-transcriptional regulation whereby thousands of transcripts are preserved for translation during later stages. A key step in translation initiation is the binding of eukaryotic initiation factor 4E (eIF4E) to the 5’ mRNA cap. Drosophila has multiple paralogs of eIF4E, including four (eIF4E-3, -4, -5, and -7) that are highly expressed in the testis. Other than eIF4E-3, none of these has been characterized genetically. Here, using CRISPR/Cas9 mutagenesis, we determined that eIF4E-5 is essential for male fertility. eIF4E-5 mutants exhibit defects during post-meiotic stages, including a fully penetrant defect in individualization, resulting in failure to produce mature sperm. eIF4E-5 protein localizes to the distal ends of elongated spermatid cysts, where it regulates non-apoptotic caspase activity during individualization by promoting local accumulation of the E3 ubiquitin ligase inhibitor Soti. eIF4E-5 mutants also have mild defects in spermatid cyst polarization, similar to mutants affecting the cytoplasmic polyadenylation-element binding protein Orb2 and atypical protein kinase C (aPKC). Our results further extend the diversity of non-canonical eIF4Es that carry out distinct spatiotemporal roles during spermatogenesis.Summary StatementThe testis-enriched translation initiation factor eIF4E-5 is needed for spermatid cyst polarization, individualization of mature sperm and male fertility in Drosophila.
Engineering selectivity of Cutibacterium acnes phages by epigenetic imprinting
Authors: Knödlseder Nastassia , Nevot Guillermo , Fábrega Maria-José , Mir-Pedrol Julia , Sanvicente-García Marta , Campamà-Sanz Nil , Lood Rolf , Güell Marc 
Published: December 2021

AbstractCutibacterium acnes (C. acnes) is a gram-positive bacterium and a member of the human skin microbiome. Despite being the most abundant skin commensal, certain members have been associated with common inflammatory disorders such as acne vulgaris. The availability of the complete genome sequences from various C. acnes clades have enabled the identification of putative methyltransferases, some of them potentially belonging to restriction-modification (R-M) systems which protect the host of invading DNA. However, little is known on whether these systems are functional in the different C. acnes strains. To investigate the activity of these putative R-M and their relevance in host protective mechanisms, we analyzed the methylome of seven representative C. acnes strains by Oxford Nanopore Technologies (ONT) sequencing. We detected the presence of a 6-methyladenine modification at a defined DNA consensus sequence in strain KPA171202 and recombinant expression of this R-M system confirmed its methylation activity. Additionally, a R-M knockout mutant verified the loss of methylation properties of the strain. We studied the potential of one C. acnes bacteriophage (PAD20) in killing various C. acnes strains and linked an increase in its specificity to phage DNA methylation acquired upon infection of a methylation competent strain. We demonstrate a therapeutic application of this mechanism where phages propagated in R-M deficient strains selectively kill R-M deficient acne-prone clades while probiotic ones remain resistant to phage infection.Graphical abstract
Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes
Authors: McAllan L. , Baranasic D. , Villicaña S. , Zhang W. , Lehne B. , Adamo M. , Jenkinson A. , Elkalaawy M. , Mohammadi B. , Hashemi M. , Yang Y. , Zudina L. , Lagou V. , Tan S. , Castillo-Fernandez J. , Soong R. , Elliott P. , Scott J. , Loh M. , Prokopenko I. , Lenhard B. , Batterham R. L. , Bell J. , Chambers J. , Kooner J. , Scott W. 
Published: December 2021

ABSTRACTDNA methylation variations are prevalent in human obesity, but evidence of a causative role in disease pathogenesis is limited. In this study, we combine epigenome-wide association and integrative genomics to investigate the impact of subcutaneous and visceral adipocyte DNA methylation variations in extreme human obesity. We identify extensive DNA methylation changes that are robustly associated with extreme obesity in combined discovery and replication analyses (N=190 samples, 691 loci in subcutaneous and 173 loci in visceral adipocytes, P<1×10-7). Using functional interaction maps and methylation-expression association testing in human adipocytes, we connect extreme obesity-associated methylation variations to transcriptomic changes at >500 target genes. We find that disease-associated methylation variations localise to active genomic regions and transcription factor binding sites, at which DNA methylation influences transcription factor-target gene co-expression relationships. In Mendelian Randomisation analyses, we infer causal effects of DNA methylation on human obesity and obesity-induced metabolic disturbances, under genetic control, at 28 independent loci. Silencing of two target genes of causal DNA methylation variations, thePRRC2AandLIMD2genes, further reveals novel metabolic effects in adipocytes. Our results indicate DNA methylation is an important determinant of human obesity and its metabolic complications, and reveal genomic and molecular mechanisms through which altered DNA methylation may impact adipocyte cellular functions.
South African Population Immunity and Severe Covid-19 with Omicron Variant
Authors: Madhi Shabir A. , Kwatra Gaurav , Myers Jonathan E. , Jassat Waasila , Dhar Nisha , Mukendi Christian K. , Nana Amit J. , Blumberg Lucille , Welch Richard , Ngorima-Mabhena Nicoletta , Mutevedzi Portia C. 
Published: December 2021

ABSTRACTBackgroundWe conducted a seroepidemiological survey from October 22 to December 9, 2021, in Gauteng Province, South Africa, to determine SARS-CoV-2 immunoglobulin G (IgG) seroprevalence primarily before the fourth wave of coronavirus disease 2019 (Covid-19), in which the B.1.1.529 (Omicron) variant was dominant. We evaluated epidemiological trends in case rates and rates of severe disease through to January 12, 2022, in Gauteng.MethodsWe contacted households from a previous seroepidemiological survey conducted from November 2020 to January 2021, plus an additional 10% of households using the same sampling framework. Dry blood spot samples were tested for anti-spike and anti-nucleocapsid protein IgG using quantitative assays on the Luminex platform. Daily case, hospital admission, and reported death data, and weekly excess deaths, were plotted over time.ResultsSamples were obtained from 7010 individuals, of whom 1319 (18.8%) had received a Covid-19 vaccine. Overall seroprevalence ranged from 56.2% (95% confidence interval [CI], 52.6 to 59.7) in children aged <12 years to 79.7% (95% CI, 77.6 to 81.5) in individuals aged >50 years. Seropositivity was more likely in vaccinated (93.1%) vs unvaccinated (68.4%) individuals. Epidemiological data showed SARS-CoV-2 infection rates increased and subsequently declined more rapidly than in previous waves. Infection rates were decoupled from Covid-19 hospitalizations, recorded deaths, and excess deaths relative to the previous three waves.ConclusionsWidespread underlying SARS-CoV-2 seropositivity was observed in Gauteng Province before the Omicron-dominant wave. Epidemiological data showed a decoupling of hospitalization and death rates from infection rate during Omicron circulation.
The expansion and severity of chronic MS lesions follows a periventricular gradient
Authors: Klistorner Samuel , Barnett Michael H , Graham Stuart L , Wang Chenyu , Klistorner Alexander 
Published: December 2021

AbstractBackground and ObjectivesExpansion of chronic lesions in MS patients and recently described CSF-related gradient of tissue damage are linked to microglial activation. The aim of the current study was to investigate whether lesion expansion is associated with proximity to ventricular CSF spaces.MethodsPre- and post-gadolinium 3D-T1, 3D FLAIR and diffusion tensor images were acquired from 36 RRMS patients. Lesional activity was analysed between baseline and 48 months at different distances from the CSF using successive 1-mm thick concentric rings radiating from the ventricles.ResultsVoxel-based analysis of the rate of lesion expansion demonstrated a clear periventricular gradient decreasing away from the ventricles. This was particularly apparent when lesions of equal diameter were analysed. Periventricular lesional tissue showed higher degree of tissue distraction at baseline that significantly increased during follow-up in rings close to CSF. This longitudinal change was proportional to degree of lesion expansion. Lesion-wise analysis revealed a gradual, centrifugal decrease in the proportion of expanding lesions from the immediate periventricular zone.DiscussionOur data suggest that chronic white matter lesions in close proximity to the ventricles are more destructive, show a higher degree of expansion at the lesion border and accelerated tissue loss in the lesion core.
Defective proinsulin handling modulates the MHC I bound peptidome and activates the inflammasome in β-cells
Authors: Khilji Muhammad Saad , Pinheiro-Machado Erika , Dahlby Tina , Aranha Ritchlynn , Buus Søren , Nielsen Morten , Klusek Justyna , Faridi Pouya , Purcell Anthony Wayne , Mandrup-Poulsen Thomas , Marzec Michal Tomasz 
Published: December 2021

ABSTRACTBackgroundHow immune-tolerance is lost to pancreatic β-cell peptides triggering autoimmune type 1 diabetes is enigmatic. We have shown that loss of the proinsulin ER chaperone glucose-regulated protein (GRP) 94 leads to mishandling of proinsulin, ER stress and activation of the inducible proteasome. We hypothesize that inadequate ER proinsulin folding capacity relative to biosynthetic need may lead to an altered β-cell MHC-I bound peptidome and inflammasome activation, sensitizing β-cells to immune attack.MethodsWe used INS-1E cells with or without GRP94 knockout (KO), or in the presence or absence of GRP94 inhibitor PU-WS13 (GRP94i, 20µM), or exposed to proinflammatory cytokines interleukin (IL)-1β or IFNγ (15 pg/ml and 10 ng/ml, respectively) for 24 hours. RT1.A (rat MHC I) expression was evaluated using flow cytometry. The total RT1.A-bound peptidome analysis was performed on cell lysates fractionated by reverse phase high performance liquid chromatography (RP-HPLC) followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). NALP1, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IκBα), and (pro) IL-1β expression and secretion were investigated by Western blotting.ResultsGRP94 KO increased RT1.A expression in β-cells as did cytokine exposure compared to relevant controls. Immunopeptidome analysis showed increased RT1.A-bound peptide repertoire in GRP94 KO/i cells as well as in the cells exposed to cytokines. The GRP94 KO/cytokine exposure groups showed partial overlap in their peptide repertoire. Notably, proinsulin-derived peptides diversity increased among the total RT1.A peptidome in GRP94 KO/i along with cytokines exposure. NALP1 expression was upregulated in GRP94 deficient cells along with decreased IκBα content while proIL-1β cellular levels declined, coupled with an increased secretion of mature IL-1β. Our results suggest that limiting β-cell proinsulin chaperoning enhances RT1.A expression, alters the MHC-I peptidome including proinsulin peptides and activates inflammatory pathways, suggesting that stress impeding proinsulin handling may sensitize β-cells to immune-attack.