bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addressing Measurement Error in Random Forests Using Quantitative Bias Analysis
Authors: Jiang Tammy , Gradus Jaimie L , Lash Timothy L , Fox Matthew P 
Published: January 2021

Abstract
Although variables are often measured with error, the impact of measurement error on machine-learning predictions is seldom quantified. The purpose of this study was to assess the impact of measurement error on the performance of random-forest models and variable importance. First, we assessed the impact of misclassification (i.e., measurement error of categorical variables) of predictors on random-forest model performance (e.g., accuracy, sensitivity) and variable importance (mean decrease in accuracy) using data from the National Comorbidity Survey Replication (2001–2003). Second, we created simulated data sets in which we knew the true model performance and variable importance measures and could verify that quantitative bias analysis was recovering the truth in misclassified versions of the data sets. Our findings showed that measurement error in the data used to construct random forests can distort model performance and variable importance measures and that bias analysis can recover the correct results. This study highlights the utility of applying quantitative bias analysis in machine learning to quantify the impact of measurement error on study results.
A natural product phillygenin suppresses osteosarcoma growth and metastasis by regulating the SHP-1/JAK2/STAT3 signaling
Authors: Ding Xiaomin , Lu Danqing , Fan Jianbo 
Published: January 2021

ABSTRACT
Osteosarcoma represents one of the most devastating cancers due to its high metastatic potency and fatality. Osteosarcoma is insensitive to traditional chemotherapy. Identification of a small molecule that blocks osteosarcoma progression has been a challenge in drug development. Phillygenin, a plant-derived tetrahydrofurofuran lignin, has shown to suppress cancer cell growth and inflammatory response. However, how phillygenin plays functional roles in osteosarcoma has remained unveiled. In this study, we showed that phillygenin inhibited osteosarcoma cell growth and motility in vitro. Further mechanistic studies indicated that phillygenin blocked STAT3 signaling pathway. Phillygenin led to significant downregulation of Janus kinase 2 and upregulation of Src homology region 2 domain-containing phosphatase 1. Gene products of STAT3 regulating cell survival and invasion were also inhibited by phillygenin. Therefore, our studies provided the first evidence that phillygenin repressed osteosarcoma progression by interfering STAT3 signaling pathway. Phillygenin is a potential candidate in osteosarcoma therapy.
Application of heavy-ion-beam irradiation to breeding large rotifer
Authors: Tsuneizumi Kazuhide , Yamada Mieko , Kim Hee-Jin , Ichida Hiroyuki , Ichinose Katsunori , Sakakura Yoshitaka , Suga Koushirou , Hagiwara Atsushi , Kawata Miki , Katayama Takashi , Tezuka Nobuhiro , Kobayashi Takanori , Koiso Masahiko , Abe Tomoko 
Published: January 2021

ABSTRACTIn larviculture facilities, rotifers are generally used as an initial food source, while a proper size of live feeds to connect rotifer and Artemia associated with fish larval growth is needed. The improper management of feed size and density induces mass mortality and abnormal development of fish larvae. To improve the survival and growth of target larvae, this study applied carbon and argon heavy-ion-beam irradiation in mutation breeding to select rotifer mutants with larger lorica sizes. The optimal irradiation conditions of heavy-ion beam were determined with lethality, reproductivity, mutant frequency, and morphometric characteristics. Among 56 large mutants, TYC78, TYC176, and TYA41 also showed active population growth. In conclusion, (1) heavy-ion-beam irradiation was defined as an efficient tool for mutagenesis of rotifers and (2) the aforementioned 3 lines that have larger lorica length and active population growth may be used as a countermeasure of live feed size gap during fish larviculcure.
SCAN-ATAC-Sim: a scalable and efficient method for simulating single-cell ATAC-seq data from bulk-tissue experiments
Authors: Chen Zhanlin , Zhang Jing , Liu Jason , Zhang Zixuan , Zhu Jiangqi , Lee Donghoon , Xu Min , Gerstein Mark 
Published: January 2021

Abstract

Summary
scATAC-seq is a powerful approach for characterizing cell-type-specific regulatory landscapes. However, it is difficult to benchmark the performance of various scATAC-seq analysis techniques (such as clustering and deconvolution) without having a priori a known set of gold-standard cell types. To simulate scATAC-seq experiments with known cell-type labels, we introduce an efficient and scalable scATAC-seq simulation method (SCAN-ATAC-Sim) that down-samples bulk ATAC-seq data (e.g. from representative cell lines or tissues). Our protocol uses a consistent but tunable signal-to-noise ratio across cell types in a scATAC-seq simulation for integrating bulk experiments with different levels of background noise, and it independently samples twice without replacement to account for the diploid genome. Because it uses an efficient weighted reservoir sampling algorithm and is highly parallelizable with OpenMP, our implementation in C++ allows millions of cells to be simulated in less than an hour on a laptop computer.

Availability and implementation
SCAN-ATAC-Sim is available at scan-atac-sim.gersteinlab.org.

Supplementary information
Supplementary data are available at Bioinformatics online.
Divergence in life history and behaviour between hybridizing Phymata ambush bugs (Heteroptera: Reduviidae)
Authors: Punzalan David , Fang Julia T , Chen William , Rowe Locke 
Published: January 2021

Abstract
Life-history variation plays a central role in evolutionary and ecological processes and might be especially pertinent to divergence in closely related species. We investigated differences in life history in a pair of parapatric species of ambush bugs (Phymata) and a putative hybrid population. Despite the evidence of gene flow among these species, we found clear divergence between these parapatric populations for a suite of juvenile and adult life-history traits, including components of fitness. The higher latitude species was also less active, suggestive of potential divergence in dispersal. Increased melanism was correlated with longevity in one species, although it was unclear whether this relationship was causal. Observed differences in the life history between species were consistent with expectations of high-latitude species putting a premium on early or rapid development and increased reproductive rates. However, these results were not consistent with ‘pace-of-life syndromes’ at the species level. Individuals from the putative hybrid zone exhibited intermediate values for most traits, although they had slower development and reduced mobility, consistent with some previous work suggesting natural selection via hybrid breakdown.
Nestling, but not adult male, barn swallows emit short calls in noisy environments
Authors: Hasegawa Masaru , Arai Emi , Nakamura Masahiko 
Published: January 2021

AbstractSome, but not all, animals cope with anthropogenic noise by changing the structure of their acoustic signals, possibly due to two interrelated factors: the design of the acoustic signals and the intrinsic biological state. Here, using the barn swallow (Hirundo rustica) that breed solitarily along streets, we studied male enticement calls and nestling food-begging calls in relation to ambient noise. The former calls are structurally quite similar to the latter, perhaps functioning as a sensory trap to exploit female parental care for nestlings. This provides a unique opportunity to study whether intrinsic biological state (i.e. developmental stage, here), virtually independent of acoustic design, matters in acoustic adaptation to anthropogenic noise. We found that the syllable length of nestling food-begging calls, but not of male enticement calls, decreased with increasing local noise levels within populations. The syllable lengths of the father’s enticement calls and those of the nestling’s food-begging calls were positively related, which explains why male enticement calls as well as nestling food-begging calls had shorter syllables in a noisy urban population compared to those in a quiet rural population. The current findings indicate that the intrinsic biological state of two acoustically similar sounds explains their differential relationships with ambient noise.
Left ventricular tamponade- pathophysiology determines the therapeutic approach: a case series
Authors: Kumar Barun , Kodliwadmath Ashwin , Singh Anupam , Upadhyay Amar , Darbari Anshuman , Duggal Bhanu 
Published: January 2021

Abstract

Background
Left ventricular (LV) tamponade is rare. LV tamponade can occur in cases of a loculated pericardial effusion overlying the LV and in cases of circumferential pericardial effusions in patients with severe pulmonary arterial hypertension (PAH). Both causes of LV tamponade share the common feature of not presenting with the classical features of cardiac tamponade. However, the therapeutic approach of the two is different.

Case summary
Here, we report two cases of LV tamponade. The first patient was a case of post-mitral valve replacement who presented with loculated posterior pericardial effusion with LV tamponade. Due to the loculated and posterior nature of the effusion, his pericardial fluid was drained from the axilla by echocardiographic and fluoroscopic guidance. The second patient presented with features of severe PAH with a circumferential pericardial effusion and LV tamponade. Due to the circumferential nature of the effusion, the pericardiocentesis was performed from the subxiphoid route.

Discussion
The pathophysiology of LV tamponade must be determined accurately before performing pericardiocentesis. Left ventricular tamponade in patients with severe PAH and non-loculated circumferential effusion can be drained from the subxiphoid route, while LV tamponade due to loculated effusion overlying LV must be drained by echocardiographic and fluoroscopic guidance from the axilla.
Functional brain isolation technique for stroke prevention in thoracic endovascular aortic repair
Authors: Tsuda Kazumasa , Washiyama Naoki , Takahashi Daisuke , Shiiya Norihiko 
Published: January 2021

Abstract
To prevent embolic stroke during thoracic endovascular aortic repair, we have adopted the brain isolation technique since June 2014 in 9 selected high-risk patients (9/134: 6.7%) having ulcerated or protruding atheromas within the proximal aorta. Cardiopulmonary bypass was used to prevent aortic atheromas from entering the brain. We used a heparin-coated closed-loop cardiopulmonary bypass system incorporating a soft reservoir bag with 1 mg/kg heparin to minimize the disadvantages of extracorporeal circulation. The bypass graft (right axillary-left carotid-left axillary) was used as an arterial inflow in patients undergoing zone-1 landing (n = 8), while peripheral cannulation into 3 brachiocephalic arteries was employed in the remaining patient. Initial pump flow was set at 1.3 l/min/m2, and native cardiac output was reduced by adjusting the reservoir bag volume. Aortography was performed to confirm non-visualization of the arch vessels before catheter manipulation. There was no mortality and 1 solitary left cerebellar infarction.
The association of migration with multiple tobacco product use among male adults in 15 low- and middle-income countries
Authors: Chen Daniel Tzu-Hsuan , Millett Christopher , Filippidis Filippos T 
Published: January 2021

Abstract
Little is known about the impact of migration on tobacco use patterns among men in low- and middle-income countries (LMICs). This study aims to explore the association between migration and tobacco use among men in LMICs. We used multilevel regression models to analyze data of 154 425 men from 15 countries from the latest wave of the Demographic and Health Survey. Results showed higher risk of single tobacco product use [relative risk ratio (RRR) = 1.22; 95% confidence interval (CI): 1.19–1.26], but importantly of dual (RR = 1.41, 95% CI: 1.36–1.49) and poly-tobacco use (RR = 1.71, 95% CI: 1.57–1.86) among migrant men compared with non-migrants.
Is COVID-19 lockdown associated with vitamin D deficiency?
Authors: Lippi Giuseppe , Ferrari Anna , Targher Giovanni 
Published: January 2021

Abstract
All vitamin D tests carried out for outpatients aged 18 years or older during the last 3 years at an Italian University Hospital was reviewed. The serum vitamin D concentrations measured since the Italian coronavirus diseases 2019 (COVID-19) lockdown to present did not significantly differ from the previous 2 years (78 vs. 77 nmol/l; P = 0.277), whilst the prevalence of vitamin D deficiency was found to be even marginally lower in 2020 (16.0% vs. 17.9%; P = 0.003). These results suggest that vitamin D deficiency in our province has not increased during the Italian COVID-19 outbreak or in correspondence with the nationwide lockdown.
TheTreponema denticolaDgcA protein (TDE0125) is a functional diguanylate cyclase
Authors: Patel Dhara T , O'Bier Nathaniel S , Schuler Edward J A , Marconi Richard T 
Published: January 2021

ABSTRACTPeriodontal disease (PD) is a progressive inflammatory condition characterized by degradation of the gingival epithelium, periodontal ligament, and alveolar bone ultimately resulting in tooth loss. Treponema denticola is a keystone periopathogen that contributes to immune dysregulation and direct tissue destruction. As periodontal disease develops, T. denticola must adapt to environmental, immunological and physiochemical changes in the subgingival crevice. Treponema denticola produces bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP), an important regulatory nucleotide. While T. denticola encodes several putative diguanylate cyclases (DGCs), none have been studied and hence the biological role of c-di-GMP in oral treponemes remains largely unexplored. Here, we demonstrate that the T. denticola open reading frame, TDE0125, encodes a functional DGC designated as DgcA (Diguanylate cyclase A). The dgcA gene is universal among T. denticola isolates, highly conserved and is a stand-alone GGEEF protein with a GAF domain. Recombinant DgcA converts GTP to c-di-GMP using either manganese or magnesium under aerobic and anaerobic reaction conditions. Size exclusion chromatography revealed that DgcA exists as a homodimer and in larger oligomers. Site-directed mutagenesis of residues that define the putative inhibitory site of DgcA suggest that c-di-GMP production is allosterically regulated. This report is the first to characterize a DGC of an oral treponeme.
Pan cancer patterns of allelic imbalance from chromosomal alterations in 33 tumor types
Authors: Sivakumar Smruthy , San Lucas F Anthony , Jakubek Yasminka A , Ozcan Zuhal , Fowler Jerry , Scheet Paul 
Published: January 2021

Abstract
Somatic copy number alterations (SCNAs) serve as hallmarks of tumorigenesis and often result in deviations from one-to-one allelic ratios at heterozygous loci, leading to allelic imbalance (AI). The Cancer Genome Atlas (TCGA) reports SCNAs identified using a circular binary segmentation algorithm, providing segment mean copy number estimates from single-nucleotide polymorphism DNA microarray total intensities (log R ratio), but not allele-specific intensities (“B allele” frequencies) that inform of AI. Our approach provides more sensitive identification of SCNAs by modeling the “B allele” frequencies jointly, thereby bolstering the catalog of chromosomal alterations in this widely utilized resource. Here we present AI summaries for all 33 tumor sites in TCGA, including those induced by SCNAs and copy-neutral loss-of-heterozygosity (cnLOH). We identified AI in 94% of the tumors, higher than in previous reports. Recurrent events included deletions of 17p, 9q, 3p, amplifications of 8q, 1q, 7p, as well as mixed event types on 8p and 13q. We also observed both site-specific and pan-cancer (spanning 17p) cnLOH, patterns which have not been comprehensively characterized. The identification of such cnLOH events elucidates tumor suppressors and multi-hit pathways to carcinogenesis. We also contrast the landscapes inferred from AI- and total intensity-derived SCNAs and propose an automated procedure to improve and adjust SCNAs in TCGA for cases where high levels of aneuploidy obscured baseline intensity identification. Our findings support the exploration of additional methods for robust automated inference procedures and to aid empirical discoveries across TCGA.
Modulation of the complex regulatory network for methionine biosynthesis in fungi
Authors: Shrivastava Manjari , Feng Jinrong , Coles Mark , Clark Benjamin , Islam Amjad , Dumeaux Vanessa , Whiteway Malcolm 
Published: January 2021

Abstract
The assimilation of inorganic sulfate and the synthesis of the sulfur-containing amino acids methionine and cysteine is mediated by a multibranched biosynthetic pathway. We have investigated this circuitry in the fungal pathogen Candida albicans, which is phylogenetically intermediate between the filamentous fungi and Saccharomyces cerevisiae. In S. cerevisiae, this pathway is regulated by a collection of five transcription factors (Met4, Cbf1, Met28, and Met31/Met32), while in the filamentous fungi the pathway is controlled by a single Met4-like factor. We found that in C. albicans, the Met4 ortholog is also a core regulator of methionine biosynthesis, where it functions together with Cbf1. While C. albicans encodes this Met4 protein, a Met4 paralog designated Met28 (Orf19.7046), and a Met31 protein, deletion, and activation constructs suggest that of these proteins only Met4 is actually involved in the regulation of methionine biosynthesis. Both Met28 and Met31 are linked to other functions; Met28 appears essential, and Met32 appears implicated in the regulation of genes of central metabolism. Therefore, while S. cerevisiae and C. albicans share Cbf1 and Met4 as central elements of the methionine biosynthesis control, the other proteins that make up the circuit in S. cerevisiae are not members of the C. albicans control network, and so the S. cerevisiae circuit likely represents a recently evolved arrangement.
Effects of the domestic thyroid stimulating hormone receptor (TSHR) variant on the hypothalamic-pituitary-thyroid axis and behavior in chicken
Authors: Fallahshahroudi Amir , Johnsson Martin , Sorato Enrico , Ubhayasekera S J Kumari A , Bergquist Jonas , Altimiras Jordi , Jensen Per 
Published: January 2021

Abstract
Domestic chickens are less fearful, have a faster sexual development, grow bigger, and lay more eggs than their primary ancestor, the red junglefowl. Several candidate genetic variants selected during domestication have been identified, but only a few studies have directly linked them with distinct phenotypic traits. Notably, a variant of the thyroid stimulating hormone receptor (TSHR) gene has been under strong positive selection over the past millennium, but it’s function and mechanisms of action are still largely unresolved. We therefore assessed the abundance of the domestic TSHR variant and possible genomic selection signatures in an extensive data set comprising multiple commercial and village chicken populations as well as wild-living extant members of the genus Gallus. Furthermore, by mean of extensive backcrossing we introgressed the wild-type TSHR variant from red junglefowl into domestic White Leghorn chickens and investigated gene expression, hormone levels, cold adaptation, and behavior in chickens possessing either the wild-type or domestic TSHR variant. While the domestic TSHR was the most common variant in all studied domestic populations and in one of two red junglefowl population, it was not detected in the other Gallus species. Functionally, the individuals with the domestic TSHR variant had a lower expression of the TSHR in the hypothalamus and marginally higher in the thyroid gland than wild-type TSHR individuals. Expression of TSHB and DIO2, two regulators of sexual maturity and reproduction in birds, was higher in the pituitary gland of the domestic-variant chickens. Furthermore, the domestic variant was associated with higher activity in the open field test. Our findings confirm that the spread of the domestic TSHR variant is limited to domesticated chickens, and to a lesser extent, their wild counterpart, the red junglefowl. Furthermore, we showed that effects of genetic variability in TSHR mirror key differences in gene expression and behavior previously described between the red junglefowl and domestic chicken.
Fall Risk-Increasing Drugs, Polypharmacy, and Falls Among Low-Income Community-Dwelling Older Adults
Authors: Ie Kenya , Chou Eric , Boyce Richard D , Albert Steven M 
Published: January 2021

Abstract

Background and Objectives
Medication exposure is a potential risk factor for falls and subsequent death and functional decline among older adults. However, controversy remains on the best way to assess medication exposure and which approach best predicts falls. The objective of the current study was to examine the association between different measures of medication exposure and falls risk among community-dwelling older adults.

Research Design and Methods
This retrospective cohort study was conducted using Falls Free PA program data and a linked prescription claims data from Pennsylvania’s Pharmaceutical Assistance Contract for the Elderly program. Participants were community-dwelling older adults living in Pennsylvania, United States. Three measures of medication exposure were assessed: (a) total number of regular medications (polypharmacy); (b) counts of potentially inappropriate medications derived from current prescription guidance tools (Fall Risk-Increasing Drugs [FRIDs], Beers Criteria); and (c) medication burden indices based on pharmacologic mechanisms (Anticholinergic Cognitive Burden, Drug Burden Index) all derived from claims data. The associations between the different medication risk measures and self-reported falls incidence were examined with univariate and multivariable negative binomial regression models to estimate incidence rate ratios (IRRs).

Results
Overall 343 older adults were included and there were 236 months with falls during 2,316 activity-adjusted person-months (10.2 falls per 100 activity-adjusted person-months). Of the 6 measures of medication risk assessed in multivariate models, only the use of 2 or more FRIDs (adjusted IRR 1.67 [95% CI: 1.04–2.68]) independently predicted falls risk. Among the 13 FRID drug classes, the only FRID class associated with an increased fall risk was antidepressants.

Discussion and Implications
The presence of multiple FRIDs in a prescription is an independent risk factor for falls, even in older adults with few medications. Further investigation is required to examine whether deprescribing focused on FRIDs effectively prevents falls among this population.