bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-Wide Association Study of Pelvic Organ Prolapse Using the Michigan Genomics Initiative
Authors: Cox Caroline K. , Pandit Anita , Zawistowski Matthew , Dutta Diptavo , Narla Goutham , Swenson Carolyn W. 
Published: May 2021

Objectives
The aim of this study was to (1) replicate previously identified genetic variants significantly associated with pelvic organ prolapse and (2) identify new genetic variants associated with pelvic organ prolapse using a genome-wide association study.

Methods
Using our institution’s database linking genetic and clinical data, we identified 1,329 women of European ancestry with an International Classification of Diseases, Ninth Revision (ICD-9)/ICD-10 code for prolapse, 767 of whom also had Current Procedural Terminology (CPT)/ICD-9/ICD-10 procedure codes for prolapse surgery, and 16,383 women of European ancestry older than 40 years without a prolapse diagnosis code as controls. Patients were genotyped using the Illumina HumanCoreExome chip and imputed to the Haplotype Reference Consortium. We tested 20 million single nucleotide polymorphisms (SNPs) for association with pelvic organ prolapse adjusting for relatedness, age, chip version, and 4 principal components. We compared our results with 18 previously identified genome-wide significant SNPs from the UK Biobank, Commun Biol (2020;3:129), and Obstet Gynecol (2011;118:1345–1353).

Results
No variants achieved genome-wide significance (P = 5 × 10−8). However, we replicated 4 SNPs with biologic plausibility at nominal significance (P ≤ 0.05): rs12325192 (P = 0.002), rs9306894 (P = 0.05), rs1920568 (P = 0.034), and rs1247943 (P = 0.041), which were all intergenic and nearest the genes SALL1, GDF7, TBX5, and TBX5, respectively.

Conclusions
Our replication of 4 biologically plausible previously reported SNPs provides further evidence for a genetic contribution to prolapse, specifically that rs12325192, rs9306894, rs1920568, and rs1247943 may contribute to susceptibility for prolapse. These and previously reported associations that have not yet been replicated should be further explored in larger, more diverse cohorts, perhaps through meta-analysis.
Origami and materials science
Authors: Liu H. , Plucinsky P. , Feng F. , James R. D. 
Published: May 2021

Origami, the ancient art of folding thin sheets, has attracted increasing attention for its practical value in diverse fields: architectural design, therapeutics, deployable space structures, medical stent design, antenna design and robotics. In this survey article, we highlight its suggestive value for the design of materials. At continuum level, the rules for constructing origami have direct analogues in the analysis of the microstructure of materials. At atomistic level, the structure of crystals, nanostructures, viruses and quasi-crystals all link to simplified methods of constructing origami. Underlying these linkages are basic physical scaling laws, the role of isometries, and the simplifying role of group theory. Non-discrete isometry groups suggest an unexpected framework for the design of novel materials.This article is part of the theme issue ‘Topics in mathematical design of complex materials’.
Nutations in growing plant shoots as a morphoelastic flutter instability
Authors: Agostinelli D. , Noselli G. , DeSimone A. 
Published: May 2021

Growing plant shoots exhibit spontaneous oscillations that Darwin observed, and termed ‘circumnutations’. Recently, they have received renewed attention for the design and optimal actuation of bioinspired robotic devices. We discuss a possible interpretation of these spontaneous oscillations as a Hopf-type bifurcation in a growing morphoelastic rod. Using a three-dimensional model and numerical simulations, we analyse the salient features of this flutter-like phenomenon (e.g. the characteristic period of the oscillations) and their dependence on the model details (in particular, the impact of choosing different growth models) finding that, overall, these features are robust with respect to changes in the details of the growth model adopted.
This article is part of the theme issue ‘Topics in mathematical design of complex materials’.
Attitudes Toward The COVID-19 Vaccine Among North Carolina Participants In The COVID-19 Community Research Partnership
Authors: Enwezor Chukwunyelu H , Peacock James E. , Edelstein Sharon L , Hinkelman Amy N , Seals Austin L , Wierzba Thomas F , Munawar Iqra , Maguire Patrick D , Lagarde William H , Runyon Michael S , Gibbs Michael A , Gallaher Thomas R , Sanders John W. , Herrington David M. 
Published: May 2021

AbstractWillingness to receive the newly developed Coronavirus Disease-2019 (COVID-19) vaccines is highly variable. To assess the receptiveness of a select sample of North Carolinians to COVID-19 vaccination, a brief survey was conducted among participants in the COVID-19 Community Research Partnership (CCRP) affiliated with five medical centers in North Carolina. A total of 20,232 CCRP participants completed a multiple choice, mini survey electronically between December 17, 2020 and January 13, 2021. Of the 20,232 survey respondents, 15,422 (76.2%) were receptive to vaccination. Vaccine receptiveness increased incrementally with age with those >70 years being the most willing to be vaccinated compared to all other age groups. Respondents with no previous COVID-19 diagnosis were more likely to accept the vaccine compared to those that have a previous COVID-19 diagnosis (76.6% vs 60.9%). Comparative analysis of gender, race/ethnicity, and residence locale revealed that women, African Americans, and suburban participants were less willing to get a COVID-19 vaccine. There was no difference in vaccine intent based on healthcare worker status. Of those unwilling to get the vaccine, 82% indicated that the reason was uncertainty about the safety and efficacy of the vaccine.
COVID-19 Fatality Rate Classification using Synthetic Minority Oversampling Technique (SMOTE) for Imbalance Class
Authors: Oladunni Timothy , Stephan Justin , Coulibaly Lala Aicha 
Published: May 2021

AbstractSARS-Cov-2 is not to be introduced anymore. The global pandemic that originated more than a year ago in Wuhan, China has claimed thousands of lives. Since the arrival of this plague, face mask has become part of our dressing code. The focus of this study is to design, develop and evaluate a COVID-19 fatality rate classifier at the county level. The proposed model predicts fatality rate as low, moderate, or high. This will help government and decision makers to improve mitigation strategy and provide measures to reduce the spread of the disease. Tourists and travelers will also find the work useful in planning of trips. Dataset used in the experiment contained imbalanced fatality levels. Therefore, class imbalance was offset using SMOTE. Evaluation of the proposed model was based on precision, F1 score, accuracy, and ROC curve. Five learning algorithms were trained and evaluated. Experimental results showed the Bagging model has the best performance.
A facile immunopeptidomics workflow for capturing the HLA-I ligandome with PEAKS XPro
Authors: Hoffman Kyle S. , Shan Baozhen , Krieger Jonathan R. 
Published: May 2021

AbstractIdentifying antigens displayed specifically on tumour cell surfaces by human leukocyte antigen (HLA) proteins is important for the development of immunotherapies and cancer vaccines. The difficulty in capturing an HLA ligandome stems from the fact that many HLA ligands are derived from splicing events or contain mutations, hindering their identification in a standard database search. To address this challenge, we developed an immunopeptidomics workflow with PEAKS XPro that uses de novo sequencing to uncover such peptides and identifies mutations for neoantigen discovery. We demonstrate the utility of this workflow by re-analyzing HLA-I ligandome datasets and reveal a vast diversity in peptide sequences among clones derived from a colorectal cancer tumour. Over 8000 peptides predicted to bind HLA-I molecules were identified by de novo sequencing only (not found in the UniProt database) and make up over 50% of identified peptides from each sample. Lastly, tumour-specific mutations and consensus sequence motif characteristics are defined. This workflow is widely applicable to any immunopeptidomic mass spectrometry dataset and does not require custom database generation for neoantigen discovery.
Heterozygous variants in KCNC2 cause a broad spectrum of epilepsy phenotypes associated with characteristic functional alterations
Authors: Schwarz Niklas , Seiffert Simone , Pendziwiat Manuela , Rademacher Annika , Brünger Tobias , Hedrich Ulrike B.S. , Augustijn Paul B , Baier Hartmut , Bayat Allan , Bisulli Francesca , Buono Russell J , Bruria Ben Zeev , Doyle Michael G , Guerrini Renzo , Heimer Gali , Iacomino Michele , Kearney Hugh , Klein Karl Martin , Kousiappa Ioanna , Kunz Wolfram S. , Lerche Holger , Licchetta Laura , Lohmann Ebba , Minardi Raffaella , McDonald Marie , Montgomery Sarah , Mulahasanovic Lejla , Oegema Renske , Ortal Barel , Papacostas Savvas S. , Ragona Francesca , Granata Tiziana , Reif Philipp S. , Rosenow Felix , Rothschild Annick , Scudieri Paolo , Striano Pasquale , Tinuper Paolo , Tanteles George A. , Vetro Annalisa , Zahnert Felix , Zara Federico , Lal Dennis , May Patrick , Muhle Hiltrud , Helbig Ingo , Weber Yvonne 
Published: May 2021

AbstractBackgroundKCNC2 encodes a member of the shaw-related voltage-gated potassium channel family (KV3.2), which are important for sustained high-frequency firing and optimized energy efficiency of action potentials in the brain.MethodsIndividuals with KCNC2 variants detected by exome sequencing were selected for clinical, further genetic and functional analysis. The cases were referred through clinical and research collaborations in our study. Four de novo variants were examined electrophysiologically in Xenopus laevis oocytes.ResultsWe identified novel KCNC2 variants in 27 patients with various forms of epilepsy. Functional analysis demonstrated gain-of-function in severe and loss-of-function in milder phenotypes as the underlying pathomechanisms with specific response to valproic acid.ConclusionThese findings implicate KCNC2 as a novel causative gene for epilepsy emphasizing the critical role of KV3.2 in the regulation of brain excitability with an interesting genotype-phenotype correlation and a potential concept for precision medicine.
T-cell and antibody immunity after COVID-19 mRNA vaccines in healthy and immunocompromised subjects-An exploratory study
Authors: Sindhi Rakesh , Ashokkumar Chethan , Spishock Brianna , Saunders Maggie , Mabasa Angelo , Sethi Pradeep , Reddy Ashok , Nibhanupudy Bobby 
Published: May 2021

AbstractBackgroundIn recent studies, up to half of immunocompromised (IC) subject populations fail to develop antibodies after COVID-19 vaccination.Purpose and MethodsHere, we explore whether T-cells which respond to the spike (S) antigenic sequence and its less conserved S1, and the conserved S2 component are present in serial samples before and after each dose of mRNA1273 or BNT162b2 vaccines in 20 healthy immunocompetent subjects. Single samples from 7 vaccinated IC subjects were also tested. Simultaneously, we measured IgG antibodies to the receptor binding domain (RBD) of S1, and anti-S IgG, and frequencies of monocytic CD14+HLA-DR-(M-MDSC) and polymorphonuclear CD14-CD15+CD11b+ (PMN-MDSC) myeloid-derived suppressor cells.ResultsIn healthy subjects, S1-, S2-, and S-reactive CD4 and CD8 T-cell frequencies showed a numeric but not statistically significant decrease after the first vaccine dose and were accompanied by increased MDSC frequencies (p<0.05). After the second dose, S2-and S-reactive CD4 and CD8 cells and MDSC approached pre-vaccination levels. In healthy subjects, a) S1-reactive CD8 frequencies were significantly higher after the second dose compared with pre-vaccination levels (p=0.015), b) anti-RBD and anti-S IgG were present in all after the second dose. Among seven IC subjects, anti-RBD and anti-S IgG were absent in 4 and 3 subjects, respectively. S1-reactive CD8 cells were identified in 2 of 4 anti-RBD negative subjects. S-reactive CD4 or CD8 cells were identified in all three anti-S negative subjects.ConclusionsIn healthy immunocompetent subjects, mRNA vaccines induce antibodies to the spike antigenic sequences and augment CD8 cells reactive to the S1 spike sequence, which is more specific for the SARS-CoV-2 virus. In this exploratory cohort of vaccinated immunocompromised subjects, S1-reactive CD8 cells can be detected in some who are negative for RBD antibody, and S-reactive T-cells are present in all who are negative for spike antibody.
Domiciliary high-flow nasal cannula oxygen therapy for stable hypercapnic COPD patients: a prospective, multicenter, open-label, randomized controlled trial
Authors: Nagata Kazuma , Horie Takeo , Chohnabayashi Naohiko , Jinta Torahiko , Tsugitomi Ryosuke , Shiraki Akira , Tokioka Fumiaki , Kadowaki Toru , Watanabe Akira , Fukui Motonari , Kitajima Takamasa , Sato Susumu , Tsuda Toru , Kishimoto Nobuhito , Kita Hideo , Mori Yoshihiro , Nakayama Masayuki , Tsuboi Tomomasa , Yoshida Makoto , Hataji Osamu , Fuke Satoshi , Kagajo Michiko , Nishine Hiroki , Kobayashi Hiroyasu , Nakamura Hiroyuki , Okuda Miyuki , Tachibana Sayaka , Takata Shohei , Osoreda Hisayuki , Minami Kenichi , Nishimura Takashi , Ishida Tadashi , Terada Jiro , Takeuchi Naoko , Kohashi Yasuo , Inoue Hiromasa , Nakagawa Yoko , Kikuchi Takashi , Tomii Keisuke ,   FLOCOP study investigators
Published: May 2021

ABSTRACTBackgroundThe effectiveness of the domiciliary use of high-flow nasal cannula oxygen therapy (HFNC) in patients with chronic hypercapnic respiratory failure due to chronic obstructive pulmonary disease (COPD) remains controversial.ObjectivesTo investigate the efficacy and safety of domiciliary HFNC use in stable hypercapnic COPD patients.MethodsThis multicenter, open-label, randomized controlled trial enrolled patients with stable hypercapnic COPD. Over 52 weeks, we compared long-term oxygen therapy (LTOT) alone versus domiciliary HFNC plus LTOT (HFNC/LTOT). The primary endpoint was the frequency of moderate/severe COPD exacerbations. We also compared changes from baseline levels in arterial blood gas, SpO2, pulmonary function, health-related quality of life (HRQOL), and a six-minute walk test.ResultsWe enrolled 104 patients in total; from these, we removed mismatching patients and then assigned 49 and 50 patients to HFNC/LTOT and LTOT groups, respectively, for safety analysis; 47 and 46 patients for HFNC/LTOT and LTOT groups, respectively, for efficacy analysis. Thirty-seven (79%) and 41 patients (89%) in HFNC/LTOT and LTOT, respectively, completed the final evaluation. HFNC significantly reduced the frequency of COPD exacerbations and prolonged the duration without moderate or severe COPD exacerbations over the 52-week study period (p = 0.002, p = 0.032, respectively). The adjusted odds ratios (95% confidence intervals [CIs]) of the frequency of COPD exacerbations in LTOT against HFNC/LTOT was 2.85 (1.48, 5.47). The median survival time (95% CI) to the first COPD exacerbation with moderate or severe for the LTOT group was 25 weeks (14.1, 47.4); however, the HFNC/LTOT group did not reach the median survival time. HFNC also caused statistically significant differences (p < 0.05) in the SpO2, FVC (%FVC), and FEV1 (%FEV1); however, these improvements were transient. There were no other improvements in arterial blood gas, pulmonary function, HRQOL, or six-minute walk test parameters. In addition, no safety concerns were identified for HFNC.ConclusionsHFNC may be a reasonable therapeutic choice in stable hypercapnic COPD patients with a history of exacerbations.Trial registration number: UMIN000028581, NCT03282019 (http://www.umin/ac.jp, https://clinicaltrials.gov/)
Persistent clotting protein pathology in Long COVID/ Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin
Authors: Pretorius Etheresia , Vlok Mare , Venter Chantelle , Bezuidenhout Johannes A. , Laubscher Gert Jacobus , Steenkamp Janami , Kell Douglas B. 
Published: May 2021

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by acute clinical pathologies, including various coagulopathies that may be accompanied by hypercoagulation and platelet hyperactivation. Recently, a new COVID-19 phenotype has been noted in patients after they have ostensibly recovered from acute COVID-19 symptoms. This new syndrome is commonly termed Long COVID/Post-Acute Sequelae of COVID-19 (PASC). Here we refer to it as Long COVID/PASC. Lingering symptoms persist for as much as 6 months (or longer) after acute infection, where COVID-19 survivors complain of recurring fatigue or muscle weakness, being out of breath, sleep difficulties, and anxiety or depression. Given that blood clots can block microcapillaries and thereby inhibit oxygen exchange, we here investigate if the lingering symptoms that individuals with Long COVID/PASC manifest might be due to the presence of persistent circulating plasma clots that are resistant to fibrinolysis. We use techniques including proteomics and fluorescence microscopy to study plasma samples from healthy individuals, individuals with Type 2 Diabetes Mellitus (T2DM), with acute COVID-19, and those with Long COVID/PASC symptoms. We show that plasma samples from Long COVID/PASC still contain large anomalous (amyloid) deposits. We also show that these anomalous deposits in both acute COVID-19 and Long COVID/PASC plasma samples are resistant to fibrinolysis (compared to plasma from controls and T2DM), even after trypsinisation. After a second trypsinization, the persistent pellet deposits were solubilized. We detected various inflammatory molecules that are substantially increased in both the supernatant and trapped in the solubilized pellet deposits of acute COVID-19 and Long COVID/PASC, versus the equivalent volume of fully digested fluid of the control samples. Of particular interest was a substantial increase in α(2)-antiplasmin (α2AP), various fibrinogen chains, as well as Serum Amyloid A (SAA) that were trapped in the solubilized fibrinolytic-resistant pellet deposits. Clotting pathologies in both acute COVID-19 infection and in Long COVID/PASC might therefore benefit from following a regime of continued anticlotting therapy to support the fibrinolytic system function.
BODY MASS INDEX TRAJECTORY BEFORE DEATH IN COMMUNITY-DWELLING OLDER ADULTS. POPULATION-BASED COHORT STUDY
Authors: Pai Hari V , Gulliford Martin C 
Published: May 2021

ABSTRACTBackground and objectiveBoth low and high body mass index (BMI) have been associated with greater mortality in older adults. This study evaluated the trajectory of BMI in the final years of life.DesignPopulation-based cohort study.SettingCommunity-dwelling adults in the English Longitudinal Study of Ageing between 1998 and 2012.MeasurementsBody mass index, years before death and all-cause mortality. Analyses were adjusted for age, gender, educational level, housing tenure and social class.ResultsData were analysed for 16,924 participants with 31,857 BMI records; mean age at study start, 61.6 (SD 10.9) years; mean BMI, 27.5 (4.7) Kg/m2. There were 3,686 participants (4,794 BMI records) who died and 13,238 participants (27,063 BMI records) who were alive at last follow-up. Mean BMI increased with age to 60-69 years but then declined, but the age-related decline was more rapid in decedents. At ages 80-89 years, mean BMI in decedents was 26.1 (4.7) compared with 27.1 (4.4) Kg/m2 in survivors. After adjusting for age and covariates, mean BMI declined in the five years before death. From 9 to 5 years before death or end of study, adjusted mean BMI was 0.51 (95% confidence interval 0.24 to 0.78) Kg/m2 lower for decedents than survivors; and from four to zero years before death, 1.55 (1.26 to 1.84) Kg/m2 lower in decedents.ConclusionsIn community-dwelling older adults, mean body mass index enters an accelerating decline during five years before death. Reverse causation may account for the association of lower BMI with mortality.
Perceptions of and obstacles to SARS-CoV-2 vaccination among adults in Lebanon: a cross-sectional online survey
Authors: Abou-Arraj Nadeem E. , Maddah Diana , Buhamdan Vanessa , Abbas Roua , Jawad Nadine , Karaki Fatima , Alami Nael H. , Geldsetzer Pascal 
Published: May 2021

ABSTRACTThe COVID-19 pandemic is an additional burden on Lebanon’s stressed population, fragmented healthcare system, and political, economic, and refugee crises. Understanding the population’s intentions to vaccinate, and perceptions of and obstacles to SARS-CoV-2 vaccination, can inform Lebanon’s vaccination efforts. We performed a cross-sectional study from 29 Jan 2021 to 11 Mar 2021 using an online questionnaire in Arabic via convenience “snowball” sampling to assess the perceptions of adults residing in Lebanon. 1,185 adults participated in the survey. % [95% CI: 43.2%-49.0%] of survey participants intended to take the SARS-CoV-2 vaccine when available to them, 19.0% [16.8%-21.4%] indicated that they would not, and 34.0% [31.3%-36.8%] were unsure. The most common reasons for hesitancy were concerns about safety, limited testing, side effects, and efficacy. Vaccine hesitancy appears to be high in Lebanon. Disseminating clear, consistent, evidence-based safety and efficacy information on vaccines may help reduce vaccine hesitancy, especially among the large proportion of adults who appear to be unsure about (rather than opposed to) vaccination.
Multi-omics analysis reveals the impact of microbiota on host metabolism in hepatic steatosis
Authors: Zeybel Mujdat , Arif Muhammad , Li Xiangyu , Altay Ozlem , Shi Mengnan , Akyildiz Murat , Saglam Burcin , Gonenli Mehmet Gokhan , Yigit Buket , Ulukan Burge , Ural Dilek , Shoaie Saeed , Turkez Hasan , Nielsen Jens , Zhang Cheng , Uhlén Mathias , Borén Jan , Mardinoglu Adil 
Published: May 2021

AbstractNon-alcoholic fatty liver disease (NAFLD) is a complex disease involving alterations in multiple biological processes regulated by the interactions between obesity, genetic background and environmental factors including the microbiome. To decipher hepatic steatosis (HS) pathogenesis by excluding critical confounding factors including genetic variants, obesity and diabetes, we characterized 56 heterogeneous NAFLD patients by generating multi-omics data including oral and gut metagenomics as well as plasma metabolomics and inflammatory proteomics data. We explored the dysbiosis in the oral and gut microbiome and revealed host-microbiome interactions based on global metabolic and inflammatory processes. We integrated this multi-omics data using the biological network and identified HS’s key features using multi-omics data. We finally predicted HS using these key features and validated our findings in a validation dataset, where we characterized 22 subjects with varying degree of HS.Significance statementThe oral and gut microbiota alterations have been linked to NAFLD. There is a lack of data on multi-omics characteristics of hepatic steatosis by exclusion of major confounding factors of obesity and metabolic syndrome. We observed that the oral and gut microbiota remodelling starts at early stages of the NAFLD spectrum, independent of obesity and metabolic syndrome. Our analysis suggested that the bacterial diversity is correlated with multi-omics signatures in NAFLD and our predictive model created based on multi-omics variables can successfully predict hepatic steatosis. The components of the multi-omics signatures may serve as biomarkers and can be pharmaceutically targeted. Future clinical trials with microbiota manipulation could consider intervention at early stages of NAFLD.