bluuebunny/crossref_metadata_2025_split huggingface dataset:
A longitudinal study of changes in new dental graduates' engagement with evidence-based practice during their transition to professional practice
Authors: Al-Yaseen Waraf , Nanjappa Sucharita , Jindal-Snape Divya , Innes Nicola 
Published: February 2022

AbstractIntroduction Clinicians' use, interpretation and application of evidence in everyday practice is fundamental to their delivery of appropriate, contemporary, high-quality dentistry. Little is known about whether new dental graduates' (NDGs') perspectives and use of evidence-based practice (EBP) change when they enter professional practice.Aim To explore changes in NDGs' perception of EBP for: self-efficacy; knowledge of EBP principles; attitudes; confidence in appraisal skills; and frequency of accessing evidence.Methods Two pre-validated instruments: knowledge, attitude, confidence and accessing EBP resources, EBP confidence scale, and clinical scenarios. NDGs from one dental school completed the questionnaire upon graduation (R1) and six to nine months into vocational dental training (R2).Results Response rates of R1 were 34 (52%) and R2, 21 (62% of R1, 32% overall). Between R1 and R2, knowledge (median [25th-75th percentiles]: R1 = 4 [2.5-4]; R2 = 3 [2.8-3], p = 0.07), self-efficacy (R1 = 645 [587-782]; R2 = 630 [550-690], p = 0.8) and scores related to knowledge of gold standards were comparable. However, attitude (R1 = 38 [34-39], R2 = 27 [25-30]), confidence in appraisal skills (R1 = 16 [14-20], R2 = 11[8-16]) and frequency of accessing evidence (R1 = 26 [22-28]; R2 = 18 [16-19]) all showed statistically significant reductions.Conclusion After six months in professional practice, NDGs showed statistically significant reductions in the value they place on EBP, their EBP-related skills and their use of reliable evidence sources. There were no differences in their 'self-efficacy' knowledge of EBP principles.
Combining p53 mRNA nanotherapy with immune checkpoint blockade reprograms the immune microenvironment for effective cancer therapy
Authors: Xiao Yuling , Chen Jiang , Zhou Hui , Zeng Xiaodong , Ruan Zhiping , Pu Zhangya , Jiang Xingya , Matsui Aya , Zhu Lingling , Amoozgar Zohreh , Chen Dean Shuailin , Han Xiangfei , Duda Dan G. , Shi Jinjun 
Published: February 2022

AbstractImmunotherapy with immune checkpoint blockade (ICB) has shown limited benefits in hepatocellular carcinoma (HCC) and other cancers, mediated in part by the immunosuppressive tumor microenvironment (TME). As p53 loss of function may play a role in immunosuppression, we herein examine the effects of restoring p53 expression on the immune TME and ICB efficacy. We develop and optimize a CXCR4-targeted mRNA nanoparticle platform to effectively induce p53 expression in HCC models. Using p53-null orthotopic and ectopic models of murine HCC, we find that combining CXCR4-targeted p53 mRNA nanoparticles with anti-PD-1 therapy effectively induces global reprogramming of cellular and molecular components of the immune TME. This effect results in improved anti-tumor effects compared to anti-PD-1 therapy or therapeutic p53 expression alone. Thus, our findings demonstrate the reversal of immunosuppression in HCC by a p53 mRNA nanomedicine when combined with ICB and support the implementation of this strategy for cancer treatment.
Immune signature of acute pharyngitis in a Streptococcus pyogenes human challenge trial
Authors: Anderson Jeremy , Imran Samira , Frost Hannah R. , Azzopardi Kristy I. , Jalali Sedigheh , Novakovic Boris , Osowicki Joshua , Steer Andrew C. , Licciardi Paul V. , Pellicci Daniel G. 
Published: February 2022

AbstractStreptococcus pyogenescauses at least 750 million infections and more than 500,000 deaths each year. No vaccine is currently available forS. pyogenesand the use of human challenge models offer unique and exciting opportunities to interrogate the immune response to infectious diseases. Here, we use high-dimensional flow cytometric analysis and multiplex cytokine and chemokine assays to study serial blood and saliva samples collected during the early immune response in human participants following challenge withS. pyogenes. We find an immune signature of experimental human pharyngitis characterised by: 1) elevation of serum IL-1Ra, IL-6, IFN-γ, IP-10 and IL-18; 2) increases in peripheral blood innate dendritic cell and monocyte populations; 3) reduced circulation of B cells and CD4+ T cell subsets (Th1, Th17, Treg, TFH) during the acute phase; and 4) activation of unconventional T cell subsets, γδTCR + Vδ2+ T cells and MAIT cells. These findings demonstrate thatS. pyogenesinfection generates a robust early immune response, which may be important for host protection. Together, these data will help advance research to establish correlates of immune protection and focus the evaluation of vaccines.
Dynamic Runx1 chromatin boundaries affect gene expression in hematopoietic development
Authors: Owens Dominic D. G. , Anselmi Giorgio , Oudelaar A. Marieke , Downes Damien J. , Cavallo Alessandro , Harman Joe R. , Schwessinger Ron , Bucakci Akin , Greder Lucas , de Ornellas Sara , Jeziorska Danuta , Telenius Jelena , Hughes Jim R. , de Bruijn Marella F. T. R. 
Published: February 2022

AbstractThe transcription factor RUNX1 is a critical regulator of developmental hematopoiesis and is frequently disrupted in leukemia. Runx1 is a large, complex gene that is expressed from two alternative promoters under the spatiotemporal control of multiple hematopoietic enhancers. To dissect the dynamic regulation of Runx1 in hematopoietic development, we analyzed its three-dimensional chromatin conformation in mouse embryonic stem cell (ESC) differentiation cultures. Runx1 resides in a 1.1 Mb topologically associating domain (TAD) demarcated by convergent CTCF motifs. As ESCs differentiate to mesoderm, chromatin accessibility, Runx1 enhancer-promoter (E-P) interactions, and CTCF-CTCF interactions increase in the TAD, along with initiation of Runx1 expression from the P2 promoter. Differentiation to hematopoietic progenitor cells is associated with the formation of tissue-specific sub-TADs over Runx1, a shift in E-P interactions, P1 promoter demethylation, and robust expression from both Runx1 promoters. Deletion of promoter-proximal CTCF sites at the sub-TAD boundaries has no obvious effects on E-P interactions but leads to partial loss of domain structure, mildly affects gene expression, and delays hematopoietic development. Together, our analysis of gene regulation at a large multi-promoter developmental gene reveals that dynamic sub-TAD chromatin boundaries play a role in establishing TAD structure and coordinated gene expression.
UINMF performs mosaic integration of single-cell multi-omic datasets using nonnegative matrix factorization
Authors: Kriebel April R. , Welch Joshua D. 
Published: February 2022

AbstractSingle-cell genomic technologies provide an unprecedented opportunity to define molecular cell types in a data-driven fashion, but present unique data integration challenges. Many analyses require “mosaic integration”, including both features shared across datasets and features exclusive to a single experiment. Previous computational integration approaches require that the input matrices share the same number of either genes or cells, and thus can use only shared features. To address this limitation, we derive a nonnegative matrix factorization algorithm for integrating single-cell datasets containing both shared and unshared features. The key advance is incorporating an additional metagene matrix that allows unshared features to inform the factorization. We demonstrate that incorporating unshared features significantly improves integration of single-cell RNA-seq, spatial transcriptomic, SNARE-seq, and cross-species datasets. We have incorporated the UINMF algorithm into the open-source LIGER R package (https://github.com/welch-lab/liger).
Broadly binding and functional antibodies and persisting memory B cells elicited by HIV vaccine PDPHV
Authors: Wang Shixia , Yates Nicole L. , Pollara Justin , Voronin Yegor , Stanfield-Oakley Sherry , Han Dong , Hu Guangnan , Li Wei , Ferrari Guido , Tomaras Georgia D. , Lu Shan 
Published: February 2022

AbstractSince publishing our original reports on the safety and immunogenicity of a polyvalent DNA prime-protein boost HIV vaccine (PDPHV) which elicited high titer antibody responses with broad specificity, neutralizing activities to multiple HIV-1 subtypes, as well as poly-functional T cell responses, accumulated findings from other HIV vaccine studies indicated the important roles of Ig isotype distribution, Fc medicated functions and the persistence of memory immune responses which were not studied in previous PDPHV related reports. The current report provides further detailed characterization of these parameters in human volunteers receiving the PDPHV regimen. Antibody responses were assessed using IgG isotype and gp70-V1V2-binding ELISAs, peptide arrays, and antibody-dependent cellular cytotoxicity (ADCC) assays. B cell ELISPOT was used to detect gp120-specific memory B cells. Our results showed that the gp120-specific antibodies were primarily of the IgG1 isotype. HIV-1 envelope protein variable regions V1 and V2 were actively targeted by the antibodies as determined by specific binding to both peptide and V1V2-carrying scaffolds. The antibodies showed potent and broad ADCC responses. Finally, the B cell ELISPOT analysis demonstrated persistence of gp120-specific memory B cells for at least 6 months after the last dose. These data indicate that broadly reactive binding Abs and ADCC responses as well as durable gp120-specific memory B cells were elicited by the polyvalent heterologous prime-boost vaccination regimens and showed great promise as a candidate HIV vaccine.
UK daily meteorology, air quality, and pollen measurements for 2016–2019, with estimates for missing data
Authors: Reani Manuele , Lowe Douglas , Gledson Ann , Topping David , Jay Caroline 
Published: February 2022

AbstractIn recent years, quantifying the impacts of detrimental air quality has become a global priority for researchers and policy makers. At present, the systems and methodologies supporting the collection and manipulation of this data are difficult to access. To support studies quantifying the interplay between common gaseous and particulate pollutants with meteorology and biological particles, this paper presents a comprehensive data-set containing daily air quality readings from the Automatic Urban and Rural Network, and pollen and weather data from Met Office monitoring stations, in the years 2016 to 2019 inclusive, for the United Kingdom. We describe (1) the sources from which the data were collected, (2) the methods used for the data cleaning process and (3) how issues related to missing values and sparse regional coverage were addressed. The resulting data-set is designed to be used ‘as is’ by those using air quality data for research; we also describe and provide open access to the methods used for curating the data to allow modification of or addition to the data-set.
Joint modeling of time to diabetic retinopathy and change in fasting blood sugar among type 2 diabetic patients, Northwest Ethiopia
Authors: Kebede Sewnet Adem , Tessema Zemenu Tadesse , Balcha Shitaye Alemu , Ayele Tadesse Awoke 
Published: February 2022

AbstractThis study aimed to assess changes in fasting blood sugar (FBS) levels, time to diabetic retinopathy (DR) and its predictors among type 2 diabetes patients in Ethiopia. An institution-based retrospective follow-up study was conducted at the University of Gondar Comprehensive Specialized Hospital. The linear mixed effect model and Cox proportional hazard models were fitted separately, and later, the two models were fitted jointly using R software. Variables with apvalue < 0.05 were considered significant predictors in the adjusted analysis. The incidence rate of DR was 2 per 100-person year of observation with a median follow-up time of 90.8 months (IQR 63.4). The current value and rate of change in FBS level were significant predictors of time to DR (AHR = 1.35; 95% CI 1.12–1.63) and (AHR = 1.70; 95% CI 1.21–2.39), respectively. Hypertension (AHR = 2.49; 95% CI 1.32–4.66), taking > 1 antidiabetic oral agent (AHR = 4.90; 95% CI 1.07–20.0) and more than 10 years duration (AHR = 0.17, 95% CI 0.06–0.46) were predictors of time to DR. This study revealed that the current value of FBS and the rate of FBS change were significantly associated with the time to DR.
Cell biological analysis reveals an essential role for Pfcerli2 in erythrocyte invasion by malaria parasites
Authors: Liffner Benjamin , Balbin Juan Miguel , Shami Gerald J. , Siddiqui Ghizal , Strauss Jan , Frölich Sonja , Heinemann Gary K. , Edwards Ella May , Alder Arne , Wichers Jan Stephan , Creek Darren J. , Tilley Leann , Dixon Matthew W. A. , Gilberger Tim-Wolf , Wilson Danny W. 
Published: February 2022

AbstractMerozoite invasion of host red blood cells (RBCs) is essential for survival of the human malaria parasite Plasmodium falciparum. Proteins involved with RBC binding and invasion are secreted from dual-club shaped organelles at the apical tip of the merozoite called the rhoptries. Here we characterise P. falciparum Cytosolically Exposed Rhoptry Leaflet Interacting protein 2 (PfCERLI2), as a rhoptry bulb protein that is essential for merozoite invasion. Phylogenetic analyses show that cerli2 arose through an ancestral gene duplication of cerli1. We show that PfCERLI2 is essential for blood-stage growth and localises to the cytosolic face of the rhoptry bulb. Inducible knockdown of PfCERLI2 led to a proportion of merozoites failing to invade and was associated with elongation of the rhoptry organelle during merozoite development and inhibition of rhoptry antigen processing. These findings identify PfCERLI2 as a protein that has key roles in rhoptry biology during merozoite invasion.
Prof. Nicolaus Friedreich und die Neuroanatomie der Pyramidenbahn
Authors: Suwa Beato 
Published: February 2022

ZUSAMMENFASSUNGHemiparesen zählen in der Neurologie noch immer zu einer der häufigsten und wichtigsten Symptome, z. B. in Folge eines Insultes, aber auch in Folge einer Rückenmarksschädigung (z. B. Brown-Sequard-Syndrom). Diese Arbeit zur Medizingeschichte beschäftigt sich mit der Aufklärung der neuroanatomischen Korrelate von Hemiparesen und Folgen anderer Schädigungen der Pyramidenbahn gegen Ende des 19. Jahrhunderts, ausgehend von einem kürzlich archivierten handgeschriebenen Fragment einer Abschrift des „Excerptenbuches“ vom berühmten Pathologen Nicolaus Friedreich aus Heidelberg. Innovative und aufwendige Tiermodelle, aber vor allem auch die Verbesserungen der Möglichkeiten der Lichtmikroskopie führten in dieser Zeit zu einem explosionsartigen Zuwachs an Wissen auf dem Gebiet der Neuroanatomie.
The Impact of “COVID-19” and “Webinar Pandemic” on Plastic Surgery Practice in Teaching Institutes and Resident Training—A Multicentric Perspective
Authors: Tripathy Satyaswarup , Mohapatra Devi Prasad , Sahu Ranjit Kumar , Mohsina Subair , Sharma Ramesh Kumar , Khan Subhendu , Renu Sharda , Singh Chandra Kunwari , Nair Suraj R. , Koliath Shijina , Pathan Imran 
Published: February 2022

AbstractIntroduction The study was carried out to quantify the changes induced by the pandemic in plastic surgery practice and training and to study the impact of the webinars on plastic surgery education from a residents’ perspective.Methods In this multicentric study, the number and type of surgeries, cause of injuries, and their regional variation during the coronavirus disease 2019 (COVID-19) period (February–September 2020) were compared with pre–COVID-19 time. An online survey on the impact of webinars was conducted for plastic surgery trainees across the country.Results There was a significant reduction in total number of surgeries (p = 0.003). The procedures for hand (p = 0.156), faciomaxillary injuries (p = 0.25), and replantations (p = 0.46) were comparable; there was a significant reduction in combined orthopedic-plastic-surgical procedures (p = 0.009) during the pandemic. There was a significant reduction in road accidents (p = 0.007) and suicidal injuries (p = 0.002) and increase in assault (p = 0.03) and domestic accidents (p = 0.01) during the COVID-19 period.A usefulness score of >8 was given for the webinars by 68.7% residents. There was no significant difference in perception of utility when correlated with the academic program at their institutes (p = 0.109); 92% opined webinars should continue in post-COVID times.Conclusion There was a drastic reduction in number of elective and emergency procedures during the COVID-19 time, negatively affecting resident training program. Majority of residents felt that webinars could prove a useful adjunct to training in formal training program in post-COVID-19 scenario.
Hernia and Abdominal Wall Reconstruction for the Colorectal Surgeon
Authors: Buxey Kenneth 
Published: February 2022

AbstractHernia remains a challenge for the colorectal surgeon both in regard to prevention of hernia, that is a common entity following colorectal surgery and in managing hernia which is often made more challenging by the co-existence of a significant colorectal-specific problem. This review outlines the extent of hernia as a problem for the colorectal surgeon and highlights contemporary approaches to dealing with patients who require both colorectal and complex hernia surgery.
A Broad Safety Assessment of the Recombinant Herpes Zoster Vaccine
Authors: Yih W Katherine , Kulldorff Martin , Dashevsky Inna , Maro Judith C 
Published: February 2022

Abstract
The recombinant herpes zoster vaccine (RZV), approved as a 2-dose series in the United States in October 2017, has proven highly effective and generally safe. However, a small risk of Guillain-Barré syndrome after vaccination was identified after approval, and questions remain about other possible adverse events. This data-mining study assessed RZV safety in the United States using the self-controlled tree-temporal scan statistic, scanning data on thousands of diagnoses recorded during follow-up to detect any statistically unusual temporal clustering of cases within a large hierarchy of diagnoses. IBM MarketScan data on commercially insured persons at least 50 years of age receiving RZV between January 1, 2018, and May 5, 2020, were used, including 56 days of follow-up; 1,014,329 doses were included. Statistically significant clustering was found within a few days of vaccination for unspecified adverse effects, complications, or reactions to immunization or other medical substances/care; fever; unspecified allergy; syncope/collapse; cellulitis; myalgia; and dizziness/giddiness. These findings are consistent with the known safety profile of this and other injected vaccines. No cluster of Guillain-Barré syndrome was detected, possibly due to insufficient sample size. This signal-detection method has now been applied to 5 vaccines, with consistently plausible results, and seems a promising addition to vaccine-safety evaluation methods.
Perfluoroalkyl substances influence DNA methylation in school-age children highly exposed through drinking water contaminated from firefighting foam: a cohort study in Ronneby, Sweden
Authors: Xu Yiyi , Lindh Christian H , Fletcher Tony , Jakobsson Kristina , Engström Karin 
Published: February 2022

AbstractPerfluoroalkyl substances (PFASs) are widespread synthetic substances with various adverse health effects. A potential mechanism of toxicity for PFASs is via epigenetic changes, such as DNA methylation. Previous studies have evaluated associations between PFAS exposure and DNA methylation among newborns and adults. However, no study has evaluated how PFASs influence DNA methylation among children of school age. In this exploratory study with school-age children exposed to PFASs through drinking water highly contaminated from firefighting foams, we aimed to investigate whether exposure to PFASs was associated with alteration in DNA methylation and epigenetic age acceleration. Sixty-three children aged 7–11 years from the Ronneby Biomarker Cohort (Sweden) were included. The children were either controls with only background exposure (n = 32; perfluorooctane sulfonic acid: median 2.8 and range 1–5 ng/ml) or those exposed to very high levels of PFASs (n = 31; perfluorooctane sulfonic acid: median 295 and range 190–464 ng/ml). These two groups were matched on sex, age, and body mass index. Genome-wide methylation of whole-blood DNA was analyzed using the Infinium MethylationEPIC BeadChip kit. Epigenetic age acceleration was derived from the DNA methylation data. Twelve differentially methylated positions and seven differentially methylated regions were found when comparing the high-exposure group to the control group. There were no differences in epigenetic age acceleration between these two groups (P = 0.66). We found that PFAS exposure was associated with DNA methylation at specific genomic positions and regions in children at school age, which may indicate a possible mechanism for linking PFAS exposure to health effects.
Pre-intervention left ventricular mechanical dispersion is increased in patients in need for pacemaker after TAVI
Authors: Kaya E , Klaeboe LG , Aaberge L , Haugaa KH , Edvardsen T , Skulstad H 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background and Purpose
Transcatheter Aortic Valve Implantation (TAVI) is an effective therapy for patients with severe aortic stenosis. Complete atrioventricular block (AVB) that requires permanent pacemaker treatment is a common complication of TAVI and it is reported in up to one fifth of patients. Prediction of this complication could be important. Global longitudinal strain (GLS) and left ventricular mechanical dispersion (LVMD) by speckle tracking echocardiography (STE) are novel techniques that detect subtle changes in myocardial function and are related to myocardial fibrosis. Thus, we aimed to investigate the association between LVMD and AVB development after TAVI.

Methods
We retrospectively screened 168 consecutive patients after TAVI. Patients with abnormal ECG and changed conduction pre- and post-TAVI were excluded. Data from the remaining 61 patients were compared to the group of 16 patients in need for a permanent pacemaker. Baseline echocardiograms recorded before TAVI were used to assess GLS and LVMD by STE (Figure).

Results
Of the 77 patients analysed, 60% were female (82 ± 7 years old). The mean GLS values were -16.8 ± 4.2% and -16.9 ± 3.7% in AVB and no AVB groups, respectively (p = 0.9). The mean LVMD was 60 ± 19 ms in AVB group and 50 ± 16 ms in no-AVB group (p = 0.04). (Table)

Conclusion
LVMD was increased in patients who developed TAVI-induced complete AVB, while GLS could not differentiate between post-procedural normal and abnormal electrical conduction. This finding may be important to identify myocardial properties associated with complete AVB after TAVI. Abstract Table Abstract Figure