bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma
Authors: Allen Pamela B. , Savas Hatice , Evens Andrew M. , Advani Ranjana H. , Palmer Brett , Pro Barbara , Karmali Reem , Mou Eric , Bearden Jeffrey , Dillehay Gary , Bayer Robert A. , Eisner Robert M. , Chmiel Joan S. , O’Shea Kaitlyn , Gordon Leo I. , Winter Jane N. 
Published: September 2020

Abstract
Pembrolizumab, a humanized IgG4 monoclonal antibody targeting programmed death-1 protein, has demonstrated efficacy in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the complete metabolic response (CMR) rate and safety of pembrolizumab monotherapy in newly diagnosed cHL, we conducted a multicenter, single-arm, phase 2 investigator-initiated trial of sequential pembrolizumab and doxorubicin, vinblastine, and dacarbazine (AVD) chemotherapy. Patients ≥18 years of age with untreated, early, unfavorable, or advanced-stage disease were eligible for treatment. Thirty patients (early unfavorable stage, n = 12; advanced stage, n = 18) were treated with 3 cycles of pembrolizumab monotherapy followed by AVD for 4 to 6 cycles, depending on stage and bulk. Twelve had either large mediastinal masses or bulky disease (&gt;10 cm). After pembrolizumab monotherapy, 11 patients (37%) demonstrated CMRs, and an additional 7 of 28 (25%) patients with quantifiable positron emission tomography computed tomography scans had &gt;90% reduction in metabolic tumor volume. All patients achieved CMR after 2 cycles of AVD and maintained their responses at the end of treatment. With a median follow-up of 22.5 months (range, 14.2-30.6) there were no changes in therapy, progressions, or deaths. No patients received consolidation radiotherapy, including those with bulky disease. Therapy was well tolerated. The most common immune-related adverse events were grade 1 rash (n = 6) and grade 2 infusion reactions (n = 4). One patient had reversible grade 4 transaminitis and a second had reversible Bell’s palsy. Brief pembrolizumab monotherapy followed by AVD was both highly effective and safe in patients with newly diagnosed cHL, including those with bulky disease. This trial was registered at www.clinicaltrials.gov as #NCT03226249.
Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: a case series
Authors: Weber Andrew G. , Chau Alice S. , Egeblad Mikala , Barnes Betsy J. , Janowitz Tobias 
Published: September 2020

Abstract
Background
Mechanically ventilated patients with COVID-19 have a mortality of 24–53%, in part due to distal mucopurulent secretions interfering with ventilation. DNA from neutrophil extracellular traps (NETs) contribute to the viscosity of mucopurulent secretions and NETs are found in the serum of COVID-19 patients. Dornase alfa is recombinant human DNase 1 and is used to digest DNA in mucoid sputum. Here, we report a single-center case series where dornase alfa was co-administered with albuterol through an in-line nebulizer system.

Methods
Demographic and clinical data were collected from the electronic medical records of five mechanically ventilated patients with COVID-19—including three requiring veno-venous extracorporeal membrane oxygenation—treated with nebulized in-line endotracheal dornase alfa and albuterol, between March 31 and April 24, 2020. Data on tolerability and response were analyzed.

Results
The fraction of inspired oxygen requirements was reduced for all five patients after initiating dornase alfa administration. All patients were successfully extubated, discharged from hospital and remain alive. No drug-associated toxicities were identified.

Conclusions
Results suggest that dornase alfa will be well-tolerated by patients with severe COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and several have been recently registered.
Selection for feed efficiency using the social effects animal model in growing Duroc pigs: evaluation by simulation
Authors: Herrera-Cáceres William , Sánchez Juan Pablo 
Published: September 2020

Abstract
Background
Traits recorded on animals that are raised in groups can be analysed with the social effects animal model (SAM). For multiple traits, this model specifies the genetic correlation structure more completely than the animal model (AM). Our hypothesis was that by using the SAM for genetic evaluation of average daily gain (ADG) and backfat thickness (BF), a high rate of improvement in feed conversion ratio (FCR) might be achieved, since unfavourable genetic correlations between ADG and BF reported in a Duroc pig line could be partially avoided. We estimated genetic and non-genetic correlations between BF, ADG and FCR on 1144 pigs using Bayesian methods considering the SAM; and responses to selection indexes that combine estimates of indirect (IGE) and direct (DGE) genetic effects for ADG and BF by stochastic simulation.

Results
Estimates of the ratio of the variance of DGE to the phenotypic variance were 0.31, 0.39 and 0.25 and those of the total genetic variance to the phenotypic variance were 0.63, 0.74 and 0.93 for ADG, BF and FCR, respectively. In spite of this, when the SAM was used to generate data and for the genetic evaluations, the average economic response was worse than that obtained when BV predictions from the AM were considered. The achieved economic response was due to a direct reduction in BF and not to an improvement in FCR.

Conclusions
Our results show that although social genetic effects play an important role in the traits studied, their proper consideration in pig breeding programs to improve FCR indirectly is still difficult. The correlations between IGE and DGE that could help to overcome the unfavourable genetic correlations between DGE did not reach sufficiently high magnitudes; also, the genetic parameters estimates from the SAM have large errors. These two factors penalize the average response under the SAM compared to the AM.
Hypercluster: a flexible tool for parallelized unsupervised clustering optimization
Authors: Blumenberg Lili , Ruggles Kelly V. 
Published: September 2020

Abstract
Background
Unsupervised clustering is a common and exceptionally useful tool for large biological datasets. However, clustering requires upfront algorithm and hyperparameter selection, which can introduce bias into the final clustering labels. It is therefore advisable to obtain a range of clustering results from multiple models and hyperparameters, which can be cumbersome and slow.

Results
We present hypercluster, a python package and SnakeMake pipeline for flexible and parallelized clustering evaluation and selection. Users can efficiently evaluate a huge range of clustering results from multiple models and hyperparameters to identify an optimal model.

Conclusions
Hypercluster improves ease of use, robustness and reproducibility for unsupervised clustering application for high throughput biology. Hypercluster is available on pip and bioconda; installation, documentation and example workflows can be found at: https://github.com/ruggleslab/hypercluster.
Transcriptome characterization of BPG axis and expression profiles of ovarian steroidogenesis-related genes in the Japanese sardine
Authors: Nyuji Mitsuo , Hongo Yuki , Yoneda Michio , Nakamura Masahiro 
Published: September 2020

AbstractBackgroundThe clupeoid fishes are ecologically and commercially important fish species worldwide that exhibit a high level of population fluctuation, accompanied by alteration of reproductive traits. However, knowledge about their reproductive physiology in order to understand mechanisms underlying such population dynamics is limited. The endocrine system along with the brain–pituitary–gonadal (BPG) axis is critical for regulating reproduction. The aims of this study were to provide transcript data and genes related to the BPG axis, and to characterize the expression profiles of ovarian steroidogenesis-related genes in the Japanese sardine (Sardinops melanostictus, Clupeidae).ResultsRNA sequencing was performed using the sardine brain, pituitary, and gonad in both sexes. A total of 290,119 contigs were obtained and 115,173 non-redundant ORFs were annotated. The genes differentially expressed between ovary and testis were strongly associated with GO terms related to gamete production. The tissue-specific profile of the abundance of transcripts was characterized for the major regulators in the BPG axis, such as gonadotropin-releasing hormone, gonadotropin, and steroidogenic enzyme. By comparing between ovary and testis, out of eight different 17β-hydroxysteroid dehydrogenase (Hsd17b) genes identified, higherhsd17b7expression was found in testis, whereas higher expression ofhsd17b8,hsd17b10,hsd17b12a, andhsd17b12bwas found in ovary. The cDNAs encoding key endocrine factors in the ovarian steroidogenic pathway were cloned, sequenced, and quantitatively assayed. In the pituitary,follicle-stimulating hormone betapeaked during vitellogenesis, whileluteinizing hormone betapeaked at the completion of vitellogenesis. In the ovary,follicle-stimulating hormone receptorandluteinizing hormone receptorwere upregulated from mid- to late phase of vitellogenesis. Furthermore, three steroidogenic enzyme genes (cyp11a1,cyp17a1, andcyp19a1a) gradually increased their expression during ovarian development, accompanying a rise in serum estradiol-17β, while3β-hydroxysteroid dehydrogenaseandsteroidogenic acute regulatory proteindid not change significantly.ConclusionsThis is the first report of deep RNA sequencing analysis of Japanese sardine, in which many key genes involved in the BPG axis were identified. Expression profiles of ovarian steroidogenesis-related genes provide a molecular basis of the physiological processes underlying ovarian development in the sardine. Our study will be a valuable resource for clarifying the molecular biology of clupeoid fishes.
Differential expression in leaves of Saccharum genotypes contrasting in biomass production provides evidence of genes involved in carbon partitioning
Authors: Correr Fernando Henrique , Hosaka Guilherme Kenichi , Barreto Fernanda Zatti , Valadão Isabella Barros , Balsalobre Thiago Willian Almeida , Furtado Agnelo , Henry Robert James , Carneiro Monalisa Sampaio , Margarido Gabriel Rodrigues Alves 
Published: September 2020

AbstractBackgroundThe development of biomass crops aims to meet industrial yield demands, in order to optimize profitability and sustainability. Achieving these goals in an energy crop like sugarcane relies on breeding for sucrose accumulation, fiber content and stalk number. To expand the understanding of the biological pathways related to these traits, we evaluated gene expression of two groups of genotypes contrasting in biomass composition.ResultsFirst visible dewlap leaves were collected from 12 genotypes, six per group, to perform RNA-Seq. We found a high number of differentially expressed genes, showing how hybridization in a complex polyploid system caused extensive modifications in genome functioning. We found evidence that differences in transposition and defense related genes may arise due to the complex nature of the polyploidSaccharumgenomes. Genotypes within both biomass groups showed substantial variability in genes involved in photosynthesis. However, most genes coding for photosystem components or those coding forphosphoenolpyruvate carboxylases(PEPCs) were upregulated in the high biomass group.Sucrose synthase(SuSy) coding genes were upregulated in the low biomass group, showing that this enzyme class can be involved with sucrose synthesis in leaves, similarly tosucrose phosphate synthase(SPS) andsucrose phosphate phosphatase(SPP). Genes in pathways related to biosynthesis of cell wall components andexpansinscoding genes showed low average expression levels and were mostly upregulated in the high biomass group.ConclusionsTogether, these results show differences in carbohydrate synthesis and carbon partitioning in the source tissue of distinct phenotypic groups. Our data from sugarcane leaves revealed how hybridization in a complex polyploid system resulted in noticeably different transcriptomic profiles between contrasting genotypes.
Oral microbial profile variation during canine ligature-induced peri-implantitis development
Authors: Qiao Shichong , Wu Dongle , Wang Mengge , Qian Shujiao , Zhu Yu , Shi Junyu , Wei Yongjun , Lai Hongchang 
Published: September 2020

Abstract
Background
Dental implants have become well-established in oral rehabilitation for fully or partially edentulous patients. However, peri-implantitis often leads to the failure of dental implants. The aim of this study was to understand the core microbiome associated with peri-implantitis and evaluate potential peri-implantitis pathogens based on canine peri-implantitis model.

Results
In this study, three beagle dogs were used to build peri-implantitis models with ligature-induced strategy. The peri-implant sulcular fluids were collected at four different phases based on disease severity during the peri-implantitis development. Microbial compositions during peri-implantitis development were monitored and evaluated. The microbes were presented with operational taxonomic unit (OTU) classified at 97% identity of the high-throughput 16S rRNA gene fragments. Microbial diversity and richness varied during peri-implantitis. At the phylum-level, Firmicutes decreased and Bacteroides increased during peri-implantitis development. At the genus-level, Peptostreptococcus decreased and Porphyromonas increased, suggesting peri-implantitis pathogens might be assigned to these two genera. Further species-level and co-occurrence network analyses identified several potential keystone species during peri-implantitis development, and some OTUs were potential peri-implantitis pathogens.

Conclusion
In summary, canine peri-implantitis models help to identify several potential keystone peri-implantitis associated species. The canine model can give insight into human peri-implantitis associated microbiota.
C-reactive protein for prediction of atrial fibrillation recurrence after catheter ablation
Authors: Meyre Pascal B. , Sticherling Christian , Spies Florian , Aeschbacher Stefanie , Blum Steffen , Voellmin Gian , Madaffari Antonio , Conen David , Osswald Stefan , Kühne Michael , Knecht Sven 
Published: September 2020

Abstract
Background
Inflammation plays an important role in the initiation and progression of atrial fibrillation (AF), but data about the relationship between subclinical inflammation and recurrence of AF after catheter ablation remains poorly studied. We aimed to assess whether plasma levels of C-reactive protein (CRP) are associated with long-term AF recurrence following catheter ablation.

Methods
Prior to the intervention, plasma CRP concentrations were measured in patients who underwent first catheter ablation for AF. AF recurrence was evaluated after 12 months and defined as any AF episode longer than 30 s recorded on either 12-lead electrocardiogram, 24-h Holter or 7-day Holter monitoring. Multivariable adjusted Cox models were constructed to examine the association of CRP levels and AF recurrence.

Results
Of the 711 patients (mean age: 61 years, 25% women) included in this study, 247 patients (35%) experienced AF recurrence after ablation. Patients who were in the highest CRP quartile had a higher rate of recurrent AF compared to those who were in the lowest quartile (53.4 vs. 33.1% at 1 year of follow-up; P = 0.004). The adjusted hazard ratios (aHR) of recurrent AF across increasing quartiles of CRP were 1.0 (reference), 1.26 (95% confidence interval [CI], 0.86–1.84), 1.15 (95% CI, 0.78–1.70) and 1.60 (95% CI, 1.10–2.34) (P trend = 0.015). A similar effect was observed when CRP was analyzed as continuous variable (aHR per unit increase, 1.21; 95% CI, 1.05–1.39; P = 0.009). When a predefined CRP cut-off of 3 mg/l was applied, patients with CRP levels of 3 mg/l or above had a higher risk of AF recurrence than those with levels below (aHR, 1.44; 95% CI, 1.06–1.95; P = 0.019).

Conclusions
Increasing pre-interventional CRP levels are associated with a higher risk of AF recurrence in patients undergoing catheter ablation for AF.

Trail registration
ClinicalTrials.gov identifier, NCT03718364.
Value of the platelet-to-lymphocyte ratio in the prediction of left ventricular thrombus in anterior ST-elevation myocardial infarction with left ventricular dysfunction
Authors: Zhang Qian , Si Daoyuan , Zhang Zhongfan , Wang Chengbing , Zheng Haikuo , Li Shouping , Huang Shijian , Zhang Wenqi 
Published: September 2020

Abstract
Background
The predictors of left ventricular thrombus (LVT) formation are not well defined in the contemporary era, especially in those patients at high risk. We aimed to evaluate whether the platelet/lymphocyte ratio (PLR) is valuable in the determination of LVT formation in patients with anterior ST-elevation myocardial infarction (STEMI) and left ventricular (LV) dysfunction.

Methods
The LVT group (n = 46) was identified from anterior STEMI patients with LV dysfunction who were treated with primary percutaneous coronary intervention (PCI) from January 2017 to December 2019 at the China-Japan Union Hospital of Jilin University. The no-LVT group (n = 92) were also selected from the same batch of patients and were age- and sex-matched to the patients with LVT. The PLR was determined at admission and was calculated as the ratio of the platelet count to the lymphocyte count using the complete blood count. The presence of LVT was determined by echocardiography.

Results
The PLR were significantly higher in patients with LVT than in no-LVT group (p = 0.001). In a receiver operator characteristic curve (ROC) analysis, using a cut-off value of 118.07 (AUC 0.673, 95% CI: 0.574–0.771, P = 0.001), the PLR could independently predict the occurrence of LVT. Multivariate analysis showed that an increased PLR (OR = 1.011, 95% CI: 1.004–1.018, P = 0.002), the presence of a left ventricular aneurysm (OR = 46.350, 95% CI: 5.659–379.615, P < 0.001) and increased DTBT (OR = 1.005, 95% CI: 1.001–1.009, P = 0.012) were independent predictors of LVT formation.

Conclusions
In acute anterior STEMI patients with LV dysfunction, an increased PLR and DTBT and the presence of an LV aneurysm were independent predictors of LVT formation. A larger prospective study is warranted to evaluate this result.

Trial registration
This study was registered (May 4, 2019) on Chinese Clinical Trial Registry (ChiCTR-DDD-17011214).
Contrasting cumulative risk and multiple individual risk models of the relationship between Adverse Childhood Experiences (ACEs) and adult health outcomes
Authors: LaNoue Marianna D. , George Brandon J. , Helitzer Deborah L. , Keith Scott W. 
Published: September 2020

Abstract
Background
A very large body of research documents relationships between self-reported Adverse Childhood Experiences (srACEs) and adult health outcomes. Despite multiple assessment tools that use the same or similar questions, there is a great deal of inconsistency in the operationalization of self-reported childhood adversity for use as a predictor variable. Alternative conceptual models are rarely used and very limited evidence directly contrasts conceptual models to each other. Also, while a cumulative numeric ‘ACE Score’ is normative, there are differences in the way it is calculated and used in statistical models. We investigated differences in model fit and performance between the cumulative ACE Score and a ‘multiple individual risk’ (MIR) model that enters individual ACE events together into prediction models. We also investigated differences that arise from the use of different strategies for coding and calculating the ACE Score.

Methods
We merged the 2011–2012 BRFSS data (N = 56,640) and analyzed 3 outcomes. We compared descriptive model fit metrics and used Vuong’s test for model selection to arrive at best fit models using the cumulative ACE Score (as both a continuous or categorical variable) and the MIR model, and then statistically compared the best fit models to each other.

Results
The multiple individual risk model was a better fit than the categorical ACE Score for the ‘lifetime history of depression’ outcome. For the outcomes of obesity and cardiac disease, the cumulative risk and multiple individual risks models were of comparable fit, but yield different and complementary inferences.

Conclusions
Additional information-rich inferences about ACE-health relationships can be obtained from including a multiple individual risk modeling strategy. Results suggest that investigators working with large srACEs data sources could empirically derive the number of items, as well as the exposure coding strategy, that are a best fit for the outcome under study. A multiple individual risk model could also be considered in addition to the cumulative risk model, potentially in place of estimation of unadjusted ACE-outcome relationships.
Performance of unanchored matching-adjusted indirect comparison (MAIC) for the evidence synthesis of single-arm trials with time-to-event outcomes
Authors: Jiang Yawen , Ni Weiyi 
Published: September 2020

Abstract
Background
The objectives of the present study were to evaluate the performance of a time-to-event data reconstruction method, to assess the bias and efficiency of unanchored matching-adjusted indirect comparison (MAIC) methods for the analysis of time-to-event outcomes, and to propose an approach to adjust the bias of unanchored MAIC when omitted confounders across trials may exist.

Methods
To evaluate the methods using a Monte Carlo approach, a thousand repetitions of simulated data sets were generated for two single-arm trials. In each repetition, researchers were assumed to have access to individual-level patient data (IPD) for one of the trials and the published Kaplan-Meier curve of another. First, we compared the raw data and the reconstructed IPD using Cox regressions to determine the performance of the data reconstruction method. Then, we evaluated alternative unanchored MAIC strategies with varying completeness of covariates for matching in terms of bias, efficiency, and confidence interval coverage. Finally, we proposed a bias factor-adjusted approach to gauge the true effects when unanchored MAIC estimates might be biased due to omitted variables.

Results
Reconstructed data sufficiently represented raw data in the sense that the difference between the raw and reconstructed data was not statistically significant over the one thousand repetitions. Also, the bias of unanchored MAIC estimates ranged from minimal to substantial as the set of covariates became less complete. More, the confidence interval estimates of unanchored MAIC were suboptimal even using the complete set of covariates. Finally, the bias factor-adjusted method we proposed substantially reduced omitted variable bias.

Conclusions
Unanchored MAIC should be used to analyze time-to-event outcomes with caution. The bias factor may be used to gauge the true treatment effect.