bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced Cognitive Burden and Increased Focus
Authors: Pfoh Elizabeth R. , Hong Sandra , Baranek Laura , Rothberg Michael B. , Beinkampen Sarah , Misra-Hebert Anita D. , Rehm Susan J. , Sikon Andrea L. 
Published: January 2022

Background:
Understanding how medical scribes impact care delivery can inform decision-makers who must balance the cost of hiring scribes with their contribution to alleviating clinician burden.

Objective:
The objective of this study was to understand how scribes impacted provider efficiency and satisfaction.

Design:
This was mixed-methods study.

Participants:
Internal and family medicine clinicians were included.

Measures:
We administered structured surveys and conducted unstructured interviews with clinicians who adopted scribes. We collected average days to close charts and quantity of after-hours clinical work in the 6 months before and after implementation using electronic health record data. We conducted a difference in difference (DID) analysis using a multilevel Poisson regression.

Results:
Three themes emerged from the interviews: (1) charting time is less after training; (2) clinicians wanted to continue working with scribes; and (3) scribes did not reduce the overall inbox burden. In the 6-month survey, 76% of clinicians endorsed that working with a scribe improved work satisfaction versus 50% at 1 month. After implementation, days to chart closure decreased [DID=0.38 fewer days; 95% confidence interval (CI): −0.61, −0.15] the average minutes worked after hours on clinic days decreased (DID=−11.5 min/d; 95% CI: −13.1, −9.9) as did minutes worked on nonclinical days (DID=−24.9 min/d; 95% CI: −28.1, −21.7).

Conclusions:
Working with scribes was associated with reduced time to close charts and reduced time using the electronic health record, markers of efficiency. Increased satisfaction accrued once scribes had experience.
Physical Versus Digital Orthognathic Surgical Planning
Authors: Ghanem Amr A. , Hamad Omar A. , Almukhtar Anas M. , Sleem Heba A. 
Published: January 2022

Objective:
Orthognathic occlusal repositioning wafers could be constructed virtually and 3D printed. This paper assessed the accuracy of a suggested virtual model to the conventionally established Glasgow model surgery.

Design:
Prospective study of the orthognathic surgery models digitally.

Participants:
Seven patients who received bi-maxillary orthognathic surgeries for correction of dentofacial deformities.

Methods:
The patients were clinically assessed and their cone beam cmputerized tomography (CBCT) studied. Model surgery of each patient was performed conventionally using face-bow and semi-adjustable articulator. Same plan was executed virtually using Mimics (Materialise, Leuven, Belgium) and 3Matic (Materialise, Leuven, Belgium). Conventionally fabricated acrylic wafers as well as 3D printed wafers were CBCT scanned with the casts reflecting the archived repositioning dictated by the wafers. Paired sample t test was performed to compare accuracy between intermediate and final occlusal repositioning wafers within conventional and virtual technique groups.

Results:
The mean deviation in intermediate wafer group was 0.64 ± 0.33 mm; whereas the mean deviation in final wafer group was 0.53 ± 0.10 mm. Paired sample t test showed that there was no statistically significant difference in mean deviation between both groups (P = 0.403).

Conclusions:
This virtual surgical wafer achieves a similar level of accuracy to the conventional Glasgow model surgery.
Temporary hold of mycophenolate boosts SARS-CoV-2 vaccination-specific humoral and cellular immunity in kidney transplant recipients
Authors: Schrezenmeier Eva , Rincon-Arevalo Hector , Jens Annika , Stefanski Ana-Luisa , Hammett Charlotte , Osmanodja Bilgin , Koch Nadine , Zukunft Bianca , Beck Julia , Oellerich Michael , Pross Vanessa , Stahl Carolin , Choi Mira , Bachmann Friederike , Liefeldt Lutz , Glander Petra , Schütz Ekkehard , Bornemann-Kolatzki Kirsten , López del Moral Covadonga , Schrezenmeier Hubert , Ludwig Carolin , Jahrsdörfer Bernd , Eckardt Kai-Uwe , Lachmann Nils , Kotsch Katja , Dörner Thomas , Halleck Fabian , Sattler Arne , Budde Klemens 
Published: January 2022

AbstractTransplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from autoimmune patients suggest that temporary MPA hold might significantly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine during temporary (5 weeks) MPA hold to 29 kidney transplant recipients, who had not mounted a humoral immune-response to previous vaccinations. Seroconversion until day 32 after vaccination was observed in 76% of patients, associated with acquisition of virus neutralizing capacity. Interestingly, 21/25 (84%) CNI-treated patients responded, but only 1/4 Belatacept-treated patients. In line with humoral responses, counts and relative frequencies of spike receptor binding domain (RBD) specific B cells were significantly increased on day 7 after vaccination, with an increase in RBD specific CD27++CD38+ plasmablasts. Whereas overall proportions of spike-reactive CD4+ T cells remained unaltered after the fourth dose, frequencies were positively correlated with specific IgG levels. Importantly, antigen-specific proliferating Ki67+ and in vivo activated PD1+ T cells significantly increased after re-vaccination during MPA hold, whereas cytokine production and memory differentiation remained unaffected. In summary, MPA hold was safe and augmented all arms of immunity during booster vaccination, suggesting its implementation in vaccination protocols for clinically stable transplant recipients.
Effect of Ozone on Allergic Airway Inflammation
Authors: Arjomandi Mehrdad , Wong Hofer , Tenney Rachel , Holland Nina , Balmes John R. 
Published: January 2022

ABSTRACTBackgroundExposure to O3 has been associated with increased risk of exacerbations of asthma, but the underlying mechanisms are not well studied. We hypothesized that O3 exposure would enhance airway inflammatory responses to allergen and the GSTM1 null genotype would modulate this enhancement.ProceduresIn a cross-over design, 10 asthmatic subjects (50% with GSTM1 null genotype) who had specific sensitization to Dermatophagoides pteronyssinus (DP) were exposed to 160 ppb O3 or filtered air (FA) control for 4 h with intermittent exercise on two separate days at least three weeks apart. 20 h post-exposure, endobronchial challenge with DP allergen, and sham normal saline (NS) instillation, were performed in two separate lung lobes. Six h later, a second bronchoscopy was performed to collect bronchoalveolar lavage (BAL) fluid from the DP- and NS-challenged lobes for analyses of cellular and biochemical markers of inflammation. Multiple variable regression was used to compare cell and cytokine responses across the four exposure groups (FA-NS, O3-NS, FA-DP, O3-DP). Effect modification by GSTM1 genotype was assessed in stratified regressions.Main FindingsBAL eosinophil and lymphocyte counts were increased in segments challenged with DP compared to segments that received sham challenges (p<0.01). DP challenge compared to sham challenge also caused a significant increase in BAL concentrations of the Th2 cytokines IL-4, IL-5, IL-10, and IL-13 (p<0.03 for all comparisons). O3 exposure did not significantly affect BAL cells or cytokine levels although BAL neutrophil count with DP challenge was non-significantly higher after O3 compared to after FA exposure (p<0.11). Compared to GSTM1-present subjects, GSTM1-null subjects had significantly reduced inflammatory responses including lower eosinophil (p<0.041) and IL-4 (p<0.014) responses to DP challenge after O3 exposure.ConclusionsO3 appears to have mixed effects on allergen-induced airway inflammation. While O3 did not cause a clear differential effect on airway cellular or cytokine responses to allergen challenge, those responses did appear to be modulated by the antioxidant enzyme, GSTM1, as evident by the attenuation of airway inflammatory responses to allergen after O3 exposure in the absence of the gene.HIGHLIGHTSOzone may increase risk of asthma exacerbation but the exact mechanisms are not clear.Susceptibility to ozone-induced airway inflammation may be associated with GSTM1 genotype.Ozone may enhance allergen-induced airway recruitment of neutrophils.The GSTM1 null mutation may decrease both eosinophil and cytokine allergic airway responses after O3 exposure.
Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses
Authors: Dosil Sara G. , López-Cobo Sheila , Rodríguez-Galán Ana , Fernández-Delgado Irene , Ramirez-Huesca Marta , Milán-Rois Paula , Castellanos Milagros , Somoza Álvaro , Gómez Manuel José , Reyburn Hugh T. , Valés-Gómez Mar , Sánchez-Madrid Francisco , Fernández-Messina Lola 
Published: January 2022

ABSTRACTNatural killer (NK) cells recognise and kill target cells undergoing different types of stress. NK cells are also capable of modulating immune responses. In particular, they regulate T cell functions. Small RNA next-generation sequencing of resting and activated NK cells and their secreted EVs led to the identification of a specific repertoire of NK-EV-associated microRNAs and their post-transcriptional modifications signature. Several microRNAs of NK-EVs, namely miR-10b-5p, miR-92a-3p and miR-155-5p, specifically target molecules involved in Th1 responses. NK-EVs promote the downregulation of GATA-3 mRNA in CD4+T cells and subsequent T-bet de-repression that leads to Th1 polarization and IFN-γ and IL-2 production. NK-EVs also have an effect on monocyte and moDCs function, driving their activation and increased presentation and co-stimulatory functions. Nanoparticle-delivered NK-EV microRNAs partially recapitulate NK-EV effectsin vivo. Our results provide new insights on the immunomodulatory roles of NK-EVs that may help to improve their use as immunotherapeutic tools.
Consensus on COVID-19 vaccination in pediatric oncohematological patients, on behalf of infectious working group of Italian Association of Pediatric Hematology Oncology
Authors: Cesaro Simone , Muggeo Paola , Zama Daniele , Cellini Monica , Perruccio Katia , Colombini Antonella , Carraro Francesca , Petris Mariagrazia , Petroni Valeria , Mascarin Maurizio , Baccelli Francesco , Soncini Elena , Mura Rosamaria , Laspina Milena , Decembrino Nunzia , Burnelli Roberta , Frenos Stefano , Castagnola Elio , Faraci Maura , Meazza Cristina , Barzaghi Federica , D’Amico Maria Rosaria , Capasso Maria , Calore Elisabetta , Ziino Ottavio , Barone Angelica , Compagno Francesca , Luti Laura , Galaverna Federica , De Santis Raffaella , Brescia Letizia , Meneghello Linda , Petrone Angelamaria , Giurici Nagua , Schumacher Fabian , Mercolini Federico 
Published: January 2022

AbstractVaccines represent the best tool to prevent the severity course and fatal consequences of pandemic by new Coronavirus 2019 infection (SARS-CoV-2). Considering the limited data on vaccination of pediatric oncohematological patients, we develop a Consensus document to support the Italian pediatric hematological oncological (AIEOP) centers in a scientifically correct communication with families and patients and to promote vaccination. The topics of the Consensus were: SARS-CoV-2 infection and disease (COVID-19) in the pediatric subjects; COVID-19 vaccines (type, schedule); which and when to vaccinate; contraindications and risk of serious adverse events; rare adverse events; third dose and vaccination after COVID-19; and other general prevention measures. Using the Delphi methodology for Consensus, 21 statements and their corresponding rationale were elaborated and discussed with the representatives of 31 centers, followed by voting. AIEOP Centers showed an overall agreement on all the statements that were therefore approved.This consensus document highlights that children and adolescents affected by hematological and oncological diseases are a fragile category. Vaccination plays an important role to prevent COVID-19, to permit the regular administration of chemotherapy or other treatments, to perform control visits and hospital admissions, and to prevent treatment delays.
Mild SARS-CoV-2 infection in rhesus macaques is associated with viral control prior to antigen-specific T cell responses in tissues
Authors: Nelson Christine E. , Namasivayam Sivaranjani , Foreman Taylor W. , Kauffman Keith D. , Sakai Shunsuke , Dorosky Danielle E. , Lora Nickiana E. ,   NIAID/DIR Tuberculosis Imaging Program, Brooks Kelsie , Potter E. Lake , Roederer Mario , Sher Alan , Weiskopf Daniela , Sette Alessandro , de Wit Emmie , Hickman Heather D. , Brenchley Jason M. , Via Laura E. , Barber Daniel L. 
Published: January 2022

ABSTRACTSARS-CoV-2 primarily replicates in mucosal sites, and more information is needed about immune responses in infected tissues. We used rhesus macaques to model protective primary immune responses in tissues during mild COVID-19. Viral RNA levels were highest on days 1-2 post-infection and fell precipitously thereafter. 18F-fluorodeoxyglucose (FDG)-avid lung abnormalities and interferon (IFN)-activated myeloid cells in the bronchoalveolar lavage (BAL) were found on days ∼3-4. Virus-specific effector CD8 and CD4 T cells were detectable in the BAL and lung tissue on days ∼7-10, after viral RNA, lung inflammation, and IFN-activated myeloid cells had declined. Notably, SARS-CoV-2-specific T cells were not detectable in the nasal turbinates, salivary glands, and tonsils on day 10 post-infection. Thus, SARS-CoV-2 replication wanes in the lungs prior to T cell responses, and in the nasal and oral mucosa despite the apparent lack of Ag-specific T cells, suggesting that innate immunity efficiently restricts viral replication during mild COVID-19.ONE SENTENCE SUMMARYSARS-CoV-2 infection leads to mild, focal lung inflammation, and type I IFN activated myeloid cells that mostly resolve prior to the influx of virus-specific effector T cells or antibody responses in rhesus macaques.
Differential Peripheral Blood Glycoprotein Profiles in Symptomatic and Asymptomatic COVID-19
Authors: Pickering Chad , Zhou Bo , Xu Gege , Rice Rachel , Ramachandran Prasanna , Huang Hector , Pham Tho D. , Schapiro Jeffrey M. , Cong Xin , Chakraborty Saborni , Edwards Karlie , Reddy Srinivasa T. , Guirgis Faheem , Wang Taia T. , Serie Daniel , Lindpaintner Klaus 
Published: January 2022

AbstractGlycosylation is the most common form of post-translational modification of proteins, critically affecting their structure and function. Using liquid chromatography and mass spectrometry for high-resolution site-specific quantification of glycopeptides coupled with high-throughput artificial intelligence-powered data processing, we analyzed differential protein glyco-isoform distributions of 597 abundant serum glycopeptides and non-glycosylated peptides in 50 individuals who had been seriously ill with COVID-19 and in 22 individuals who had recovered after an asymptomatic course of COVID-19. As additional comparison reference phenotypes, we included 12 individuals with a history of infection with a common cold coronavirus, 16 patients with bacterial sepsis, and 15 healthy subjects without history of coronavirus exposure. We found statistically significant differences, at FDR<0.05, for normalized abundances of 374 of the 597 peptides and glycopeptides interrogated, between symptomatic and asymptomatic COVID-19 patients. Similar statistically significant differences were seen when comparing symptomatic COVID-19 patients to healthy controls (350 differentially abundant peptides and glycopeptides) and common cold coronavirus seropositive subjects (353 differentially abundant peptides and glycopeptides). Among healthy controls and sepsis patients, 326 peptides and glycopeptides were found to be differentially abundant, of which 277 overlapped with biomarkers that showed differential expression between symptomatic COVID-19 cases and healthy controls. Among symptomatic COVID-19 cases and sepsis patients, 101 glycopeptide and peptide biomarkers were found to be statistically significantly abundant. Using both supervised and unsupervised machine learning techniques, we found specific glycoprotein profiles to be strongly predictive of symptomatic COVID-19 infection. LASSO-regularized multivariable logistic regression and K-means clustering yielded accuracies of 100% in an independent test set and of 96% overall, respectively. Our findings are consistent with the interpretation that a majority of glycoprotein modifications observed which are shared among symptomatic COVID-19 and sepsis patients likely represent a generic consequence of a severe systemic immune and inflammatory state. However, there are glyco-isoform changes that are specific and particular to severe COVID-19 infection. These may be representative of either COVID-19-specific consequences or of susceptibility to or predisposition for a severe course of the disease. Our findings support the potential value of glycoproteomic biomarkers in the biomedical understanding, and, potentially, the clinical management of serious acute infectious conditions.
Innate and adaptive immune defects associated with lower SARS-CoV-2 BNT162b2 mRNA vaccine response in elderly people
Authors: Vitallé Joana , Pérez-Gómez Alberto , Ostos Francisco José , Gasca-Capote Carmen , Jiménez-León María Reyes , Bachiller Sara , Rivas-Jeremías Inmaculada , del Mar Silva-Sánchez Maria , Ruiz-Mateos Anabel , López-Cortes Luis Fernando , Rafii-El-Idrissi Benhnia Mohammed , Ruiz-Mateos Ezequiel 
Published: January 2022

SUMMARYThe immune factors associated with impaired SARS-CoV-2 vaccine response in the elderly are mostly unknown. We studied old and young people vaccinated with SARS-CoV-2 BNT162b2 mRNA before and after the first and second dose. Aging was associated with a lower anti-RBD IgG levels and a decreased magnitude and polyfunctionality of SARS-CoV-2 specific T cell response. The dramatic decrease in thymic function in the elderly, which fueled alteration in T cell homeostasis, and lower CD161+ T cell levels were associated with decreased T cell response two months after vaccination. Additionally, a deficient dendritic cell (DC) homing, activation and Toll like receptor (TLR)-mediated function, along with a proinflammatory functional profile in monocytes, were observed in the elderly, which was also related to lower specific T cell response after vaccination. These findings might be relevant for the improvement of the current vaccination strategies and for the development of new vaccine prototypes.
Genome-wide Association Study of Pulmonary Function in Europeans and Africans from the UK Biobank Identifies Distinct Variants
Authors: Sinkala Musalula , Elsheikh Samar S. M. , Mbiyavanga Mamana , Cullinan Joshua , Mulder Nicola J. 
Published: January 2022

AbstractPulmonary function is an indicator of well-being, and pulmonary pathologies are the third major cause of death worldwide. FEV1, FVC, and PEF are quantitively used to assess pulmonary function. We conducted a genome-wide association analysis of pulmonary function in 383,471 individuals of European and 5,978 African descent represented in the UK Biobank. Here, we report 817 variants in Europeans and 3 in Africans associated (p-values < 5 × 10−8) with three pulmonary function parameters; FEV1, FVC and PEF. In addition to 377 variants in Europeans previously reported to be associated with phenotypes related to pulmonary function, we identified 330 novel loci, including an ISX intergenic variant rs369476290 on chromosome 22 in Africans and a KDM2A intron variant rs12790261 on chromosome 11 in Europeans. Remarkably, we find no shared variants among Africans and Europeans. Enrichment analyses of variants separately for each ancestry background revealed significant enrichment for terms related to pulmonary phenotypes in Europeans but not Africans. Further analysis of studies of pulmonary phenotypes revealed individuals of European background are disproportionally overrepresented in datasets compared to Africans, with the gap widening over the past five years. Our findings offer a better understanding of the different variants that modify pulmonary function in Africans and Europeans, a significant finding for future GWAS studies and medicine.
BNT162b2 post-exposure-prophylaxis against COVID-19
Authors: Shmuelian Zohar , Warszawer Yehuda , Or Omri , Arbel-Alon Sagit , Giladi Hilla , Tsadok Meytal Avgil , Cohen Roy , Shefer Galit , Maruotti Antonello , Lasinio Giovanna Jona , Galun Eithan 
Published: January 2022

AbstractBackgroundDuring the COVID-19 pandemic, post-exposure-prophylaxis is not a practice. Following exposure, only patient isolation is imposed. Moreover, no therapeutic prevention approach is applied. We asked whether evidence exists for reduced mortality rate following post-exposure-prophylaxis.MethodsTo estimate the effectiveness of post-exposure-prophylaxis, we obtained data from the Israeli Ministry of Health (MoH) registry. The study population consisted of Israeli residents aged 12 years and older, identified for the first time as PCR-positive for SARS-CoV-2, between December 20th, 2020 (the beginning of the vaccination campaign) and October 7th, 2021. We compared “recently injected” patients - that proved PCR-positive on the same day or on one of the five consecutive days after first vaccination (representing an unintended post-exposure-prophylaxis), to unvaccinated control group.ResultsAmong Israeli residents identified PCR-positive for SARS-CoV-2, 11,690 were found positive on the day they received their first vaccine injection (BNT162b2) or on one of the 5 days thereafter. In patients over 65 years, 143 deaths occurred among 1413 recently injected (10.12%) compared to 280 deaths among the 1413 unvaccinated (19.82%), odd ratio (OR) 0.46 (95% confidence interval (CI), 0.36 to 0.57; P<0.001). The most significant reduction in the death toll was observed among the 55 to 64 age group, with 8 deaths occurring among the 1322 recently injected (0.61%) compared to 43 deaths among the 1322 unvaccinated control (3.25%), OR 0.18 (95% CI, 0.07 to 0.39; P<0.001).ConclusionPost-exposure-prophylaxis is effective against death in COVID-19 infection.Israeli MoH Registry NumberHMO-0372-20
Multi-omics reveals principles of gene regulation and pervasive non-productive transcription in the human cytomegalovirus genome
Authors: Jürges Christopher Sebastian , Lodha Manivel , Khanh Le-Trilling Vu Thuy , Bhandare Pranjali , Wolf Elmar , Zimmermann Albert , Trilling Mirko , Prusty Bhupesh , Dölken Lars , Erhard Florian 
Published: January 2022

AbstractFor decades, human cytomegalovirus (HCMV) was thought to express ≈200 viral proteins during lytic infection. In recent years, systems biology approaches uncovered hundreds of additional viral gene products and suggested thousands of viral sites of transcription initiation. Despite all available data, the molecular mechanisms of HCMV gene regulation remain poorly understood. Here, we provide a unifying model of productive HCMV gene expression employing transcription start site profiling combined with metabolic RNA labeling as well as integrative computational analysis of previously published big data. This approach defined the expression of >2,600 high confidence viral transcripts and explained the complex kinetics of viral protein expression by cumulative effects of translation of incoming virion-associated RNA, multiple transcription start sites with distinct kinetics per viral open reading frame, and differences in viral protein stability. Most importantly, we identify pervasive transcription of transient RNAs as a common feature of this large DNA virus with its human host.