bluuebunny/crossref_metadata_2025_split huggingface dataset:
International Center-Level Variation in Utilization of Completion Lymph Node Dissection and Adjuvant Systemic Therapy for Sentinel Lymph Node-Positive Melanoma at Major Referral Centers
Authors: Broman Kristy K. , Hughes Tasha M. , Bredbeck Brooke C. , Sun James , Kirichenko Dennis , Carr Michael J. , Sharma Avinash , Bartlett Edmund K. , Nijhuis Amanda A.G. , Thompson John F. , Hieken Tina J. , Kottschade Lisa , Downs Jennifer , Gyorki David E. , Stahlie Emma , van Akkooi Alexander , Ollila David W. , O’shea Kristin , Song Yun , Karakousis Giorgos , Moncrieff Marc , Nobes Jenny , Vetto John , Han Dale , Hotz Meghan , Farma Jeffrey M. , Deneve Jeremiah L. , Fleming Martin D. , Perez Matthew , Baecher Kirsten , Lowe Michael , Bagge Roger Olofsson , Mattsson Jan , Lee Ann Y. , Berman Russell S. , Chai Harvey , Kroon Hidde M. , Teras Juri , Teras Roland M. , Farrow Norma E. , Beasley Georgia M. , Hui Jane Yuet Ching , Been Lukas , Kruijff Schelto , Sinco Brandy , Sarnaik Amod A. , Sondak Vernon K. , Zager Jonathan S. , Dossett Lesly A. ,   for the International High Risk Melanoma Consortium
Published: January 2022

Objective:
The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma.

Summary Background Data:
Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization.

Methods:
We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics.

Results:
Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients.

Conclusions:
There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.
Who was wearing a mask in 2021? Update on gender-, age-, and location-related differences during the COVID-19 pandemic
Authors: Haischer Michael H. , Beilfuss Rachel N. , Hart Meggie Rose , Opielinski Lauren , Schmit Emma , Wrucke David , Zhao Helena , Uhrich Toni D. , Hunter Sandra K. 
Published: January 2022

AbstractPrevious observational work from 2020 demonstrated gender-, age-, and location-related differences in mask-wearing behavior, despite the efficacy and public health messaging that emphasized face coverings in combatting the spread of COVID-19. In 2021, COVID-19 vaccinations and a corresponding change in public health policy became new considerations in deciding personal protective behaviors. To provide an update on mask wearers and resistors approximately one year after our initial study, we observed shoppers (n = 6,118) entering retail stores using the same experimental methodology. Approximately 26% of individuals wore a mask. Mask wearing has decreased across demographic groups compared to 2020. Aligning with previous findings, females were ∼1.5x more likely to be observed wearing a mask than males, and the odds of observing a shopper wearing a mask in a suburban or urban area was far greater than at rural stores (∼5.7x and ∼3.3x, respectively). Gender and location are confirmed to be significant and stable factors that impact mask-wearing behavior in the United States during the COVID-19 pandemic. The impact of age on mask wearing was heavily reduced compared to 2020, potentially due to the availability of COVID-19 vaccines and change in mask guidance for vaccinated individuals.
Predicting the Degree of Distracted Driving Based on fNIRS Functional Connectivity: A Pilot Study
Authors: Ogihara Takahiko , Tanioka Kensuke , Hiroyasu Tomoyuki , Hiwa Satoru 
Published: January 2022

AbstractDistracted driving is one of the main causes of traffic accidents. By predicting the attentional state of drivers, it is possible to prevent distractions and promote safe driving. In this study, we developed a model that could predict the degree of distracted driving based on brain activity. Changes in oxyhemoglobin concentrations were measured in drivers while driving a real car using functional near-infrared spectroscopy (fNIRS). A regression model was constructed for each participant using functional connectivity as an explanatory variable and break reaction time to random beeps while driving as an objective variable. As a result, we were able to construct a prediction model for 11 of the 12 participants. Furthermore, the regression model with the highest prediction accuracy for each participant was analyzed to gain a better understanding of the neural basis of distracted driving. The 11 models were classified into five clusters by hierarchical clustering based on their functional connectivity edges used in each cluster. The results showed that the combinations of the dorsal attention network (DAN)-sensory motor network (SMN) and DAN-ventral attention network (VAN) connections were common in all clusters and that these networks were essential to predict the degree of distraction in complex multitask driving. They also confirmed the existence of multiple types of prediction models with different within- and between-network connectivity patterns. These results indicate that it is possible to predict the degree of distracted driving based on the brain activity of the driver during actual driving. These results are expected to contribute to the development of safe driving systems and elucidation of the neural basis of distracted driving.
Analysis of Fatality Impact and Seroprevalence Surveys in a Community Sustaining a SARS-CoV-2 Superspreading Event
Authors: Richter Enrico , Liebl Dominik , Schulte Bianca , Lehmann Nils , Fuhrmann Christine , Jöckel Karl-Heinz , Ioannidis John P.A. , Streeck Hendrik 
Published: January 2022

AbstractThere is ongoing debate on the COVID-19 infection fatality rate (IFR) and the impact of COVID-19 on overall population mortality. Here, we addressed these issues in a community in Germany with a major superspreader event analyzing deaths over time as well as auditing death certificates in the community.18 deaths that occurred within the first 6 months of the pandemic in the community had a positive test for SARS-CoV-2. Six out of 18 SARS-CoV-2+ deaths had non-COVID-19 related causes of death (COD). Individuals with confirmed infection and COVID-19 COD typically died of respiratory failure (75%) and tended to have fewer reported comorbidities (p=0.029). Duration between first confirmed infection and death was negatively associated to COVID-19 being COD (p=0.04). Repeated seroprevalence essays on an original sample of 587 individuals in three visits showed modest increases in seroprevalence over time, and substantial seroreversion (30% [27/90] (95% CI: [20.5%; 39.5%])). IFR estimates accordingly varied depending on COVID-19 death attribution and seroprevalence caveats. Careful ascertainment and audit of COVID-19 deaths are important in understanding the impact of the pandemic.
Using quantitative magnetic resonance imaging to track cerebral alterations in multiple sclerosis brain: a longitudinal study
Authors: Vandeleene Nora , Guillemin Camille , Dauby Solène , Requier Florence , Charonitis Maëlle , Chylinski Daphne , Balteau Evelyne , Maquet Pierre , Lommers Emilie , Phillips Christophe 
Published: January 2022

AbstractQuantitative MRI quantifies tissue microstructural properties and supports the characterization of cerebral tissue damages. With an MPM protocol, 4 parameter maps are constructed: MTsat, PD, R1 and R2*, reflecting tissue physical properties associated with iron and myelin contents. Thus, qMRI is a good candidate for in vivo monitoring of cerebral damage and repair mechanisms related to MS. Here, we used qMRI to investigate the longitudinal microstructural changes in MS brain.Seventeen MS patients (age 25-65, 11 RRMS) were scanned on a 3T MRI, in two sessions separated with a median of 30 months, and the parameters evolution was evaluated within several tissue classes: NAWM, NACGM and NADGM, as well as focal WM lesions. An individual annual rate of change for each qMRI parameter was computed, and its correlation to clinical status was evaluated. For WM plaques, three areas were defined, and a GLMM tested the effect of area, time points, and their interaction on each median qMRI parameter value.Patients with a better clinical evolution, i.e., clinically stable or improving state, showed positive annual rate of change in MTsat and R2* within NAWM and NACGM, suggesting repair mechanisms in terms of increased myelin content and/or axonal density as well as edema/inflammation resorption. When examining WM lesions, qMRI parameters within surrounding NAWM showed microstructural modifications, even before any focal lesion is visible on conventional FLAIR MRI.The results illustrate the benefit of multiple qMRI data in monitoring subtle changes within normal appearing brain tissues and plaque dynamics in relation with tissue repair or disease progression.Key pointsPatients with a better clinical evolution showed microstructural improvement in term of MTsat and R2* increase in their normal appearing tissue, suggesting repair mechanisms.Using qMRI allows to detect modifications in tissue microstructure in normal appearing tissues surrounding lesions several months before they are visible on conventional MRI.
Comparison of total and neutralizing SARS-CoV-2 spike antibodies against omicron and other variants in paired samples after two or three doses of mRNA vaccine
Authors: Debes Amanda K. , Xiao Shaoming , Egbert Emily R. , Caturegli Patrizio , Sitaras Ioannis , Pekosz Andrew , Milstone Aaron M. 
Published: January 2022

AbstractRecognizing that anti-SARS-CoV-2 antibody levels wane over time following the 2-dose SARS-CoV-2 mRNA series, the FDA approved a booster dose for people greater than 12 years old. Limited data exist on whether a booster dose of the mRNA vaccine results in greater antibody protection than the primary series. We examined total and neutralizing antibodies to the spike protein of SARS-CoV-2, and neutralizing antibodies against Washington-1 (WA-1) and variants of concern (VOC) including Beta, Delta and Omicron in a longitudinal cohort. Healthcare workers (HWs) were included in the analysis if serum was collected 1) within 14-44 days post-dose2 of an mRNA SARS-CoV-2 vaccine (Timepoint 1, TP1), or 2) at least 8 months post-dose2 (Timepoint 2, TP2), or 3) within 14-44 days following mRNA booster (Timepoint 3, TP3). HWs with prior covid-positive PCR were excluded. We found that there is little to no neutralizing capability following a 2-dose mRNA vaccine series against the omicron variant, and neutralizing capacity to any variant strain tested has been lost by 8-months post two-dose vaccination series. However, the mRNA booster series eliminates the immune escape observed by the omicron variant with the two-dose series. Neutralizing titers were significantly higher for all variants post-boost compared to the titers post two-dose series. The longitudinal nature of our cohort facilitated the analysis of paired samples pre and post boost, showing a greater than 15-fold increase in neutralization against omicron post-boost in these paired samples. An mRNA booster dose provides greater quantity and quality of antibodies compared to a two-dose regimen and is critical to provide any protection against the omicron variant.
Phenome-wide association study of loci harboring de novo tandem repeat mutations in UK Biobank exomes
Authors: Wendt Frank R , Pathak Gita A , Polimanti Renato 
Published: January 2022

ABSTRACTBackgroundTandem repeats (TRs) are a major source of variation in the human genome under-investigated by large-scale genetic studies. When present in coding regions, TRs may have large effects on protein structure and function contributing to health and disease.MethodsIn a family-based design of 39 European ancestry trios from the UK Biobank (UKB), the GangSTR and MonSTR methods were used to identify de novo TRs in whole-exome sequences. TRs were annotated for association with gene expression and gene set enrichment. The loci harboring de novo TRs were investigated in a phenome-wide association study in up to 148,607 unrelated UKB participants of European descent. Linear and logistic regression included age, sex, sex×age, age2, sex×age2, and ten within-ancestry principal components as covariates. TR loci were fine-mapped to identify likely causal associations.ResultsThere were 427 mutated TRs with a trend towards expansions versus contractions (χ2=5.46, df=1, P=0.019). These TRs were enriched for targets of the tumor suppressor microRNA-184 (21.1-fold, P=4.30×10−5). There were 123 TR-phenotype associations with posterior probabilities>0.95. These were related to body structure, cognition, and cardiovascular, metabolic, psychiatric, and respiratory outcomes. The most significant was between NCOA6-[GT]N and “ease of skin tanning” (beta=0.069, se=0.003, P=1.51×10−155). There were several loci with large likely causal effects on tissue microstructure, including the association of FAN1-[TG]N with carotid intima-media thickness (mean thickness: beta=5.22, se=1.08, P=1.22×10−6; maximum thickness: beta=6.44, se=1.32, P=1.12×10−6.ConclusionsCombined with the TR de novo mutational background characterized herein, TR-phenotype associations contribute clear and testable hypotheses of dose-dependent TR implications linking genetic variation and protein structure with health and disease outcomes.
mRNA vaccine boosting enhances antibody responses against SARS-CoV-2 Omicron variant in patients with antibody deficiency syndromes
Authors: Zimmerman Ofer , Altman Doss Alexa Michelle , Kaplonek Paulina , VanBlargan Laura A. , Liang Chieh-Yu , Chen Rita E. , Monroy Jennifer Marie , Wedner H. James , Kulczycki Anthony , Mantia Tarisa L. , O’Shaughnessy Caitlin C. , Davis-Adams Hannah G. , Bertera Harry L. , Adams Lucas J. , Raju Saravanan , Zhao Fang R. , Rigell Christopher J. , Biason Dy Tiffany , Kau Andrew L. , Ren Zhen , Turner Jackson , O’Halloran Jane A. , Presti Rachel M. , Fremont Daved H , Kendall Peggy L. , Ellebedy Ali H. , Alter Galit , Diamond Michael S. 
Published: January 2022

ABSTRACTPatients with primary antibody deficiency syndromes (PAD) have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed PAD patients after SARS-CoV-2 vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, FcγR binding, and neutralizing activities. Immunoglobulin replacement products had low anti-spike and receptor binding domain (RBD) titers and neutralizing activity. In COVID-19-naive PAD patients, anti-spike and RBD titers increased after mRNA vaccination but decreased to pre-immunization levels by 90 days. Patients vaccinated after SARS-CoV-2 infection developed higher responses comparable to healthy donors. Most vaccinated PAD patients had serum neutralizing antibody titers above an estimated correlate of protection against ancestral SARS-CoV-2 and Delta virus but not against Omicron virus, although this was improved by boosting. Thus, currently used immunoglobulin replacement products likely have limited protective activity, and immunization and boosting of PAD patients with mRNA vaccines should confer at least short-term immunity against SARS-CoV-2 variants, including Omicron.
On health effects of resveratrol in wine. A bibliometric view based on papers having achieved a high citation impact within the scientific discourse
Authors: Haunschild Robin , Marx Werner 
Published: January 2022

AbstractWe analyzed 3344 publications that are concerned with the health-related effects of resveratrol that occurs in wine and grapes. We found that the publication activity increased until 2010 and decreased slightly afterwards. The most frequent author keywords were classified into six groups: (1) beverages-related keywords, (2) compounds-related keywords, (3) diseases-related keywords, (4) effects-related keywords, (5) mechanisms-related keywords, and (6) broader keywords. By means of reference publication year spectroscopy, we analyzed and discussed the most frequently cited references (i.e., key papers) within the publication set. A rather large portion of the key papers takes a positive attitude and reports about health effects of resveratrol, although limited data in humans preclude drawing unambiguous conclusions on the health-related benefits of resveratrol. From our analysis, we could not identify specific publications that provide a distinct change of direction of the ongoing scientific discourse. Moderate red wine consumption seems to have the potential of being health promoting, whereas excessive alcohol consumption can induce liver cirrhosis and cancer.
Interventions designed to improve vaccination uptake: Scoping review of systematic reviews and meta-analyses - (version 1)
Authors: Heneghan CJ , Plüddemann A , Spencer EA , Brassey J , Rosca EC , Onakpoya IJ , Evans DH , Conly JM , Jefferson T 
Published: January 2022

ABSTRACTBackgroundResources to ensure high vaccination uptake differ widely across countries, but the best use of these precious resources is unclear. To better meet immunization programmes’ a pressing need to understand what works, particularly in low-resource settings, the World Health Organization commissioned a scoping view.MethodsWe conducted a scoping review of interventions designed to increase vaccination uptake, including systematic reviews and meta-analyses of interventional studies. We searched the following electronic databases: MEDLINE, Cochrane Database of Systematic Reviews, EMBASE, Epistemonikos, Google Scholar, LILACs and TRIP database until 01 July 2021 and hand-searched the reference lists of included articles. We included systematic reviews if they summarized studies with quantitative data on the impact on vaccine uptake for any age group. To assess review quality, we used a modified AMSTAR score. To evaluate the quality of the evidence in included reviews, we used the Grading of Recommendations Assessment, Development and Evaluation (GRADE).ResultsThe final analysis set included 107 full-text reviews. Publication of reviews increased markedly over time, from seven reviews in 2010 to 38 reviews filtered in 2021. We conducted quality assessments for 72 reviews (132 outcomes). Based on the AMSTAR criteria, 40 included reviews (56%) received a quality rating of good, while the remaining 32 (44%) were of moderate quality. Only 13 reviews summarized data primarily for low- and middle-income countries (LMIC). The interventions were commonly multi-component, educational or reminder interventions; the description of intervention components was suboptimal and heterogeneous across most reviews. Effect estimates were available for 73 outcomes; in 52 (71%) of these, interventions led to statistically significant higher vaccine uptake compared with controls.ConclusionsThe literature has a large number of relevant systematic reviews on interventions to increase vaccine uptake, with an increased publication rate over time. However, problems with the definitions and the current reporting of vaccine uptake evidence make it difficult to determine what works best in low-resource settings.
A phenome-wide association study identifies effects of copy number variation of VNTRs and multicopy genes on multiple human traits
Authors: Garg Paras , Jadhav Bharati , Lee William , Rodriguez Oscar L. , Martin-Trujillo Alejandro , Sharp Andrew J. 
Published: January 2022

AbstractThe human genome contains tens of thousands of large tandem repeats and hundreds of genes that show common and highly variable copy number changes. Due to their large size and repetitive nature, these Variable Number Tandem Repeats (VNTRs) and multicopy genes are generally recalcitrant to standard genotyping approaches, and as a result this class of variation is poorly characterized. However, several recent studies have demonstrated that copy number variation of VNTRs can modify local gene expression, epigenetics and human traits, indicating that many have a functional role. Here, using read depth from whole genome sequencing to profile copy number, we report results of a phenome-wide association study (PheWAS) of VNTRs and multicopy genes in a discovery cohort of ∼35,000 samples, identifying 32 traits associated with copy number of 38 VNTRs and multicopy genes at 1% FDR. We replicated many of these signals in an independent cohort, and observed that VNTRs showing trait associations were significantly enriched for expression QTLs with nearby genes, providing strong support for our results. Fine-mapping studies indicated that in the majority (∼90%) of cases, the VNTR and multicopy genes we identified represent the causal variants underlying the observed associations. Furthermore, several lie in regions where prior SNV-based GWAS have failed to identify any significant associations with these traits. Our study indicates that copy number of VNTRs and multicopy genes contributes to diverse human traits, and suggests that complex structural variants potentially explain some of the so-called “missing heritability” of SNV-based GWAS.
Sex differences, cross-ancestry generalizability, and noise-smoking interactions in the polygenic architecture of hearing loss in adults
Authors: De Angelis Flavio , Zeleznik Oana A. , Wendt Frank R. , Pathak Gita A. , Tylee Daniel S. , De Lillo Antonella , Koller Dora , Cabrera-Mendoza Brenda , Clifford Royce E , Maihofer Adam X. , Nievergelt Caroline M. , Curhan Gary C. , Curhan Sharon G. , Polimanti Renato 
Published: January 2022

AbstractWe conducted a comprehensive genome-wide investigation of hearing loss (HL) in 748,668 adult participants of the UK Biobank, the Nurses’ Health Studies (I and II), the Health Professionals Follow-up Study, and the Million Veteran Program. We identified 54 risk loci and characterized HL polygenic architecture, exploring sex differences, polygenic risk across ancestries, tissue-specific transcriptomic regulation, cause-effect relationships with genetically-correlated traits, and gene interactions with HL environmental risk factors. Our transcriptomic regulation analysis highlighted the potential role of the central nervous system in HL pathogenesis. This was supported by the multivariate interaction analysis that showed how genes involved in brain development interact with sex, noise pollution, and tobacco smoking in relation to their HL associations. Additionally, the genetically-informed causal inference analysis showed that HL is linked to many physical and mental health outcomes. These results provide many novel insights into the complex biology and epidemiology of HL in adults.