bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between obstructive sleep apnea and sleep spindles in middle-aged and older men: a community-based cohort study
Authors: Parker Jesse L , Melaku Yohannes Adama , D’Rozario Angela L , Wittert Gary A , Martin Sean A , Catcheside Peter G , Lechat Bastien , Teare Alison J , Adams Robert J , Appleton Sarah L , Vakulin Andrew 
Published: December 2021

Abstract

Study Objectives
Sleep spindles show morphological changes in obstructive sleep apnea (OSA). However, previous small studies have limited generalizability, leaving associations between OSA severity measures and spindle metrics uncertain. This study examined cross-sectional associations between OSA severity measures and spindle metrics among a large population-based sample of men.

Methods
Community-dwelling men with no previous OSA diagnosis underwent home-based polysomnography. All-night EEG (F4-M1) recordings were processed for artifacts and spindle events identified using previously validated algorithms. Spindle metrics of interest included frequency (Hz), amplitude (µV2), overall density (11–16 Hz), slow density (11–13 Hz), and fast density (13–16 Hz) (number/minute). Multivariable linear regression models controlling for demographic, biomedical, and behavioral confounders were used to examine cross-sectional associations between OSA severity measures and spindle metrics.

Results
In adjusted analyses, higher apnea-hypopnea index (AHI/h, as a continuous variable) and percentage total sleep time with oxygen saturation &lt;90% (TST90) were associated with decreased slow spindle density (AHI, B = −0.003, p = 0.032; TST90, B = −0.004, p = 0.047) but increased frequency (AHI, B = 0.002, p = 0.009; TST90, B = 0.002, p = 0.043). Higher TST90 was also associated with greater spindle amplitude (N2 sleep, B = 0.04, p = 0.011; N3 sleep, B = 0.11, p &lt; 0.001). Furthermore, higher arousal index was associated with greater spindle amplitude during N2 sleep (B = 0.31, p &lt; 0.001) but decreased overall density (B = −1.27, p = 0.030) and fast density (B = −4.36, p = 0.028) during N3 sleep.

Conclusions
Among this large population-based sample of men, OSA severity measures were independently associated with spindle abnormalities. Further population studies are needed to determine associations between spindle metrics and functional outcomes.
The preparation phase in the multiphase optimization strategy (MOST): a systematic review and introduction of a reporting checklist
Authors: Landoll Ryan R , Vargas Sara E , Samardzic Kristen B , Clark Madison F , Guastaferro Kate 
Published: December 2021

Abstract
Multicomponent behavioral interventions developed using the multiphase optimization strategy (MOST) framework offer important advantages over alternative intervention development models by focusing on outcomes within constraints relevant for effective dissemination. MOST consists of three phases: preparation, optimization, and evaluation. The preparation phase is critical to establishing the foundation for the optimization and evaluation phases; thus, detailed reporting is critical to enhancing rigor and reproducibility. A systematic review of published research using the MOST framework was conducted. A structured framework was used to describe and summarize the use of MOST terminology (i.e., preparation phase and optimization objective) and the presentation of preparation work, the conceptual model, and the optimization. Fifty-eight articles were reviewed and the majority focused on either describing the methodology or presenting results of an optimization trial (n = 38, 66%). Although almost all articles identified intervention components (96%), there was considerable variability in the degree to which authors fully described other elements of MOST. In particular, there was less consistency in use of MOST terminology. Reporting on the MOST preparation phase is varied, and there is a need for increased focus on explicit articulation of key design elements and rationale of the preparation phase. The proposed checklist for reporting MOST studies would significantly advance the use of this emerging methodology and improve implementation and dissemination of MOST. Accurate reporting is essential to reproducibility and rigor of scientific trials as it ensures future research fully understands not only the methodology, but the rationale for intervention and optimization decisions.
Waiting for the Doctor: Managing Time and Emotion in the British National Health Service, 1948–80
Authors: Moore Martin D 
Published: December 2021

Abstract
This article examines patients’ and doctors’ emotional and psychological entanglements with the development of appointment systems in British general practice between the 1948 and 1980. Waiting, especially in the form of the queue, has been subject to recent historical analyses. However, the focus has often been on negative emotional responses, on how waiting has been politicized, and on the disciplinary power of the waiting room. Frameworks of rationalization and discipline have also dominated historical and sociological assessments of temporal regulation, and especially the rise of standardized, ordered, clock and calendar time that appointments embodied. Though productive, focusing too closely on these processes in relation to time and waiting risks underplaying the complex affective life of regulatory technologies, for both their operators and their subjects. By focusing tightly on how myriad, often contradictory, responses to appointment systems operated within the setting of post-war general practice, this article looks to place such emotional and psychological relations in historical context. In so doing, it develops recent work on the emotional history of the National Health Service and, by extension, of the diverse affective and temporal modes of the British welfare state.
Cost and cost-effectiveness of dolutegravir-based antiretroviral regimens: an economic evaluation of a clinical trial
Authors: Jamieson Lise , Serenata Celicia , Makhubele Lebogang , Sokhela Simiso , Mashabane Nkuli , Akpomiemie Godspower , Johnson Leigh F. , Venter Willem D.F. , Meyer-Rath Gesine 
Published: December 2021

Background:
HIV programmes world-wide currently make decisions regarding new antiretroviral therapy (ART) regimens with less side-effects and higher resistance barriers, which may improve adherence and viral suppression. Economic evaluation helps inform these decisions.

Methods:
We conducted an economic evaluation of three ART regimens included in the ADVANCE trial from the provider's perspective: tenofovir alafenamide (TAF)/emtricitabine (FTC)+dolutegravir (DTG) and tenofovir disoproxil fumarate (TDF)/FTC+DTG, compared with TDF/FTC/efavirenz (EFV). We used top–down and bottom–up cost analysis with resource utilization based on trial data and adjusted to emulate routine care. We estimated the cost-effectiveness of each regimen as cost per person virally suppressed or retained and per life-year saved, at 48 and 96 weeks.

Results:
Though the DTG-based trial arms were 2% more costly than TDF/FTC/EFV, both had slightly lower cost-per-outcome ($9783 and $9929/patient virally suppressed for TDF/FTC+DTG and TAF/FTC+DTG, respectively) than TDF/FTC/EFV ($10 365). The trial cost per additional virally suppressed patient, compared with TDF/FTC/EFV, was lower in the TDF/FTC+DTG arm ($2967) compared with TAF/FTC+DTG ($3430). In routine care, cost per virally suppressed patient was estimated as similar between TDF/FTC+DTG ($426) and TDF/FTC/EFV ($424) but more costly under TAF/FTC+DTG. Similar results were seen in the cost per additional person retained across scenarios. When modelled over 20 years, TDF/FTC+DTG was more cost-effective than TAF/FTC+DTG ($10 341 vs $41 958/life-year saved).

Conclusion:
TDF/FTC+DTG had similar costs per outcome as TDF/FTC/EFV in the routine care scenario but TDF/FTC+DTG was more cost-effective when modelled over 20 years.
AImmune: a new blood-based machine learning approach to improving immune profiling analysis on COVID-19 patients
Authors: Han Runpeng Harris , Zhang Xi Tom 
Published: December 2021

AbstractA massive number of transcriptomic profiles of blood samples from COVID-19 patients has been produced since pandemic COVID-19 begins, however, these big data from primary studies have not been well integrated by machine learning approaches. Taking advantage of modern machine learning arthrograms, we integrated and collected single cell RNA-seq (scRNA-seq) data from three independent studies, identified genes potentially available for interpretation of severity, and developed a high-performance deep learning-based deconvolution model AImmune that can predict the proportion of seven different immune cells from the bulk RNA-seq results of human peripheral mononuclear cells. This novel approach which can be used for clinical blood testing of COVID-19 on the ground that previous research shows that mRNA alternations in blood-derived PBMCs may serve as a severity indicator. Assessed on real-world data sets, the AImmune model outperformed the most recognized immune profiling model CIBERSORTx. The presented study showed the results obtained by the true scRNA-seq route can be consistently reproduced through the new approach AImmune, indicating a potential replacing the costly scRNA-seq technique for the analysis of circulating blood cells for both clinical and research purposes.
Genetic architecture and genomic prediction accuracy of apple quantitative traits across environments
Authors: Jung Michaela , Keller Beat , Roth Morgane , Aranzana Maria José , Auwerkerken Annemarie , Guerra Walter , Al-Rifaï Mehdi , Lewandowski Mariusz , Sanin Nadia , Rymenants Marijn , Didelot Frédérique , Dujak Christian , Font i Forcada Carolina , Knauf Andrea , Laurens François , Studer Bruno , Muranty Hélène , Patocchi Andrea 
Published: December 2021

AbstractImplementation of genomic tools is desirable to increase the efficiency of apple breeding. The apple reference population (apple REFPOP) proved useful for rediscovering loci, estimating genomic prediction accuracy, and studying genotype by environment interactions (G×E). Here we show contrasting genetic architecture and genomic prediction accuracies for 30 quantitative traits across up to six European locations using the apple REFPOP. A total of 59 stable and 277 location-specific associations were found using GWAS, 69.2% of which are novel when compared with 41 reviewed publications. Average genomic prediction accuracies of 0.18–0.88 were estimated using single-environment univariate, single-environment multivariate, multi-environment univariate, and multi-environment multivariate models. The G×E accounted for up to 24% of the phenotypic variability. This most comprehensive genomic study in apple in terms of trait-environment combinations provided knowledge of trait biology and prediction models that can be readily applied for marker-assisted or genomic selection, thus facilitating increased breeding efficiency.
Structure and conservation of amyloid spines from the Candida albicans Als5 adhesin including similarity to human LARKS
Authors: Golan Nimrod , Perov Sergei Schwartz , Landau Meytal , Lipke Peter N. 
Published: December 2021

ABSTRACTCandida Als family adhesins mediate adhesion to biological and abiotic substrates, as well as fungal cell aggregation and fungal-bacterial co-aggregation. The activity of at least two family members, Als5 and Als1, is dependent on amyloid-like protein aggregation that is initiated by shear force. Each Als adhesin has a ∼300-residue N-terminal Ig-like/invasin region. The following 108-residue, low complexity, threonine-rich (T) domain unfolds under shear to expose a critical amyloid-forming segment 322SNGIVIVATTRTV334 at the interface between the Ig-like/invasin domain 2 and the T domain of Candida albicans Als5. Amyloid prediction programs identified six potential amyloidogenic sequences in the Ig/invasin region and three others in the T domain of C. albicans Als5. Peptides derived from four of these sequences formed fibrils that bound thioflavin T, the amyloid indicator dye, and three of these revealed atomic-resolution structures of cross-β spines. These are the first atomic-level structures for fungal adhesins. One of these segments, from the T domain, revealed kinked β-sheets, similarly to LARKS (Low-complexity, Amyloid-like, Reversible, Kinked segments) found in human functional amyloids. Based on the cross-β structures in Als proteins, we use evolutionary arguments to identify functional amyloidogenic sequences in other fungal adhesins. Thus, cross-β structures are often involved in fungal pathogenesis and potentially in antifungal therapy.ImportanceFungal adhesins form cell-to-cell bonds in biofilms. Many of the cellular interactions are dependent on formation of amyloid-like cross-β protein aggregates. Such structures are called ‘functional amyloids’ because they perform physiological activities and they are dependent on the same types of protein interactions that form the more familiar amyloid deposits in neurodegenerative diseases. We have identified sequence segments that form cross-β structures in the Als5 adhesin from the human pathogen Candida albicans. Such sequences are widespread among ALS family adhesins, including those from other human pathogens including Candida auris. Moreover, we revealed a structural similarity in a segment originating from Als5 threonine-rich low complexity region to human LARKS, pointing on a common structural motif coding for functional amyloids in different kingdoms of life.
Functional classification and validation of yeast prenylation motifs using machine learning and genetic reporters
Authors: Berger Brittany M. , Yeung Wayland , Goyal Arnav , Zhou Zhongliang , Hildebrandt Emily , Kannan Natarajan , Schmidt Walter K. 
Published: December 2021

AbstractProtein prenylation by farnesyltransferase (FTase) is often described as the targeting of a cysteine-containing motif (CaaX) that is enriched for aliphatic amino acids at the a1 and a2 positions, while quite flexible at the X position. Prenylation prediction methods often rely on these features despite emerging evidence that FTase has broader target specificity than previously considered. Using a machine learning approach and training sets based on canonical (prenylated, proteolyzed, and carboxymethylated) and recently identified shunted motifs (prenylation only), this study aims to improve prenylation predictions with the goal of determining the full scope of prenylation potential among the 8000 possible Cxxx sequence combinations. Further, this study aims to subdivide the prenylated sequences as either shunted (i.e., uncleaved) or cleaved (i.e., canonical). Predictions were determined for Saccharomyces cerevisiae FTase and compared to results derived using currently available prenylation prediction methods. In silico predictions were further evaluated using in vivo methods coupled to two yeast reporters, the yeast mating pheromone a-factor and Hsp40 Ydj1p, that represent proteins with canonical and shunted CaaX motifs, respectively. Our machine learning based approach expands the repertoire of predicted FTase targets and provides a framework for functional classification.
Potassium effects on NCC are attenuated during inhibition of Cullin E3-ubiquitin ligases
Authors: Murali Sathish K , Little Robert , Poulsen Søren B , Ferdaus Mohammed Z , Ellison David H , McCormick James A , Fenton Robert A 
Published: December 2021

AbstractThe thiazide sensitive sodium-chloride co-transporter (NCC) plays a vital role in maintaining sodium (Na+) and potassium (K+) homeostasis. NCC activity is modulated by the with-no-lysine kinases 1 and 4 (WNK1 and WNK4), the abundance of which are controlled by the RING-type E3 ligase Cullin 3 (Cul3) and its substrate adapter Kelch-like protein 3. Dietary K+ intake has an inverse correlation with NCC activity, but the mechanism underlying this phenomenon remains to be fully elucidated. Here, we investigated the involvement of other members of the Cullin family in mediating K+ effects on NCC phosphorylation (active form) and abundance. In kidneys from mice fed diets varying in K+ content, there were negative correlations between NCC (phosphorylated and total) and active (neddylated) forms of Cullins (Cul1, 3, 4 and 5). High dietary K+ effects on phosphorylated NCC were attenuated in Cul3 mutant mice (CUL3-Het/Δ9). Short-term (30 min) and long-term (24 h) alterations in the extracellular K+ concentration did not affect Cullin neddylation levels in ex vivo renal tubules. Short-term, the ability of high extracellular K+ to decrease NCC phosphorylation was preserved in the presence of MLN4924 (pan Cullin inhibitor), but the response to low extracellular K+ was absent. Long-term, MLN4924 attenuated the effects of high extracellular K+ on NCC phosphorylation and responses to low extracellular K+ were absent. Our data suggest that in addition to Cul3, other Cullins are involved in mediating the effects of K+ on NCC phosphorylation and abundance.
Benefits of living closer to kin vary by genealogical relationship in a territorial mammal
Authors: Walmsley Sam F. , Boutin Stan , Dantzer Ben , Lane Jeffrey E. , Coltman David W. , McAdam Andrew G. 
Published: December 2021

AbstractWhile cooperative interactions among kin are a key building block in the societies of group-living species, their importance for species with more variable social environments is unclear. North American red squirrels (Tamiasciurus hudsonicus) defend individual territories in dynamic neighbourhoods and are known to benefit from living among familiar conspecifics, but not relatives. However, kin-directed behaviours may be restricted to specific genealogical relationships or strongly mediated by geographic distance, masking their influence at broader scales. Using distance between territories as a proxy for the ability of individuals to interact, we estimated the influence of primary kin (parents, offspring, siblings) on the annual survival and reproductive success of red squirrels. This approach revealed associations between fitness and access to kin, but only for certain genealogical relationships and fitness components. For example, females had enhanced annual survival when living closer to their daughters, though the reverse was not true. Most surprising was the finding that males had higher annual reproductive success when living closer to their father, suggesting possible recognition and cooperation among fathers and sons. Together, these findings point to unexpected nuance in the fitness consequences of kinship dynamics for a species that is territorial and largely solitary.
Endogenous giant viruses contribute to intraspecies genomic variability in the model green alga Chlamydomonas reinhardtii
Authors: Moniruzzaman Mohammad , Aylward Frank O. 
Published: December 2021

AbstractChlamydomonas reinhardtii is an important eukaryotic alga that has been studied as a model organism for decades. Despite extensive history as a model system, phylogenetic and genetic characteristics of viruses infecting this alga have remained elusive. We analyzed high-throughput genome sequence data of C. reinhardtii field isolates, and in six we discovered sequences belonging to endogenous giant viruses that reach up to several hundred kilobases in length. In addition, we have also discovered the entire genome of a closely related giant virus that is endogenized within the genome of Chlamydomonas incerta, the closest sequenced phylogenetic relatives of C. reinhardtii. Endogenous giant viruses add hundreds of new gene families to the host strains, highlighting their contribution to the pangenome dynamics and inter-strain genomic variability of C. reinhardtii. Our findings suggest that the endogenization of giant viruses can have important implications for structuring the population dynamics and ecology of protists in the environment.
Retinoid-X Receptor Agonists Increase Thyroid Hormone Competence in Lower Jaw Remodeling of Pre-Metamorphic Xenopus laevis tadpoles
Authors: Mengeling Brenda J. , Vetter Lara F. , Furlow J. David 
Published: December 2021

AbstractThyroid hormone (TH) signaling plays critical roles during vertebrate development, including regulation of skeletal and cartilage growth. TH acts through its receptors (TRs), nuclear hormone receptors (NRs) that heterodimerize with Retinoid-X receptors (RXRs), to regulate gene expression. A defining difference between NR signaling during development compared to in adult tissues, is competence, the ability of the organism to respond to an endocrine signal. Amphibian metamorphosis, especially in Xenopus laevis, the African clawed frog, is a well-established in vivo model for studying the mechanisms of TH action during development. Previously, we’ve used one-week post-fertilization X. laevis tadpoles, which are only partially competent to TH, to show that in the tail, which is naturally refractive to exogenous T3 at this stage, RXR agonists increase TH competence, and that RXR antagonism inhibits the TH response. Here, we focused on the jaw that undergoes dramatic TH-mediated remodeling during metamorphosis in order to support new feeding and breathing styles. We used a battery of approaches in one-week-old tadpoles, including quantitative morphology, differential gene expression and whole mount cell proliferation assays, to show that both pharmacologic (bexarotene) and environmental (tributyltin) RXR agonists potentiated TH-induced responses but were inactive in the absence of TH; and the RXR antagonist UVI 3003 inhibited TH action. At this young age, the lower jaw has not developed to the point that T3-induced changes produce an adult-like jaw morphology, and we found that increasing TH competence with RXR agonists did not give us a more natural-metamorphic phenotype, even though Bex and TBT significantly potentiated cellular proliferation and the TH induction of runx2, a transcription factor critical for developing cartilage and bone. Prominent targets of RXR-mediated TH potentiation were members of the matrix metalloprotease family, suggesting that RXR potentiation may emphasize pathways responsible for rapid changes during development.