bluuebunny/crossref_metadata_2025_split huggingface dataset:
Facing the challenge of polypharmacy when prescribing for older people with cardiovascular disease. A review by the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy
Authors: Tamargo Juan , Kjeldsen Keld Per , Delpón Eva , Semb Anne Grete , Cerbai Elisabetta , Dobrev Dobromir , Savarese Gianluigi , Sulzgruber Patrick , Rosano Giuseppe , Borghi Claudio , Wassmann Sven , Torp-Pedersen Christian Tobias , Agewall Stefan , Drexel Heinz , Baumgartner Iris , Lewis Basil , Ceconi Claudio , Kaski Juan Carlos , Niessner Alexander 
Published: January 2022

AbstractPopulation ageing has resulted in an increasing number of older people living with chronic diseases (multimorbidity) requiring five or more medications daily (polypharmacy). Ageing produces important changes in the cardiovascular system and represents the most potent single cardiovascular risk factor. Cardiovascular diseases (CVDs) constitute the greatest burden for older people, their caregivers, and healthcare systems.Cardiovascular pharmacotherapy in older people is complex because age-related changes in body composition, organ function, homeostatic mechanisms, and comorbidities modify the pharmacokinetic and pharmacodynamic properties of many commonly used cardiovascular and non-cardiovascular drugs. Additionally, polypharmacy increases the risk of adverse drug reactions and drug interactions, which in turn can lead to increased morbi-mortality and healthcare costs. Unfortunately, evidence of drug efficacy and safety in older people with multimorbidity and polypharmacy is limited because these individuals are frequently underrepresented/excluded from clinical trials. Moreover, clinical guidelines are largely written with a single-disease focus and only occasionally address the issue of coordination of care, when and how to discontinue treatments, if required, or how to prioritize recommendations for patients with multimorbidity and polypharmacy.This review analyses the main challenges confronting healthcare professionals when prescribing in older people with CVD, multimorbidity, and polypharmacy. Our goal is to provide information that can contribute to improving drug prescribing, efficacy, and safety, as well as drug adherence and clinical outcomes.
Beta blockers and long-term outcome after coronary artery bypass grafting: a nationwide observational study
Authors: Lindgren Martin , Nielsen Susanne J , Björklund Erik , Pivodic Aldina , Perrotta Sossio , Hansson Emma C , Jeppsson Anders , Martinsson Andreas 
Published: January 2022

Abstract

Aims
Beta blockers are associated with improved outcomes for selected patients with cardiovascular disease. We assessed long-term utilization of beta blockers after coronary artery bypass grafting (CABG) and its association with outcome.

Methods and results
All 35 184 patients in Sweden who underwent first-time isolated CABG between 1 January 2006 and 31 December 2017 and were followed for at least 6 months were included in a nationwide observational study. Multivariable Cox regression models using time-updated data on dispensed prescriptions were used to assess associations between different types of beta blockers and outcomes. The primary outcome was major adverse cardiovascular events (MACEs), a composite of all-cause mortality, stroke, and myocardial infarction (MI). Subgroup analyses were performed in patients with and without previous MI, heart failure, and reduced left ventricular ejection fraction (LVEF). Median follow-up was 5.2 years (range 0–11). At baseline, 33 159 (94.2%) patients were dispensed beta blockers, 30 563 (92.2%) of which were cardioselective beta blockers. After 10 years, the dispensing of cardioselective beta blockers had declined to 73.7% of all patients. Ongoing treatment with cardioselective beta blockers was associated with a slight reduction in MACEs [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.89–0.98, P = 0.0063]. The reduction was largely driven by a reduced risk of MI (HR 0.83, 95% CI 0.75–0.92, P = 0.0003), while there was no significant reduction in all-cause mortality (HR 0.99, 95% CI 0.93–1.05) and stroke (HR 0.96, 95% CI 0.87–1.05). The reduced risk for MI was consistent in all the investigated subgroups.

Conclusion
Ongoing treatment with cardioselective beta blockers after CABG is associated with a reduction in MACEs, mainly because of reduced long-term risk for MI. The association between cardioselective beta blockers and MI was consistent in patients with and patients without previous MI, heart failure, atrial fibrillation, or reduced LVEF.
Dipping pattern and short-term blood pressure variability are stronger predictors of cardiovascular events than average 24-h blood pressure in young hypertensive subjects
Authors: Palatini Paolo , Reboldi Gianpaolo , Saladini Francesca , Angeli Fabio , Mos Lucio , Rattazzi Marcello , Vriz Olga , Verdecchia Paolo 
Published: January 2022

Abstract

Aims
The role of increased blood pressure (BP) variability and a blunted day-night BP drop is still being debated, particularly in young hypertensive subjects. We investigated the contribution of BP variability and day-night BP changes combined to cardiovascular events in initially untreated young hypertensive individuals.

Methods and results
We selected 1794 subjects aged ≤45 years from the HARVEST and the PIUMA studies, two long-term observational studies in subjects with hypertension. The outcome was a composite pool of non-fatal myocardial infarction or stroke, heart failure needing hospitalization, death from cardiovascular causes, and myocardial or limb revascularization procedures. During an 11.3-year follow-up, 140 cardiovascular events were accrued. A multivariable Cox model which included BP variability and non-dipping was more informative (Akaike Information Criterion = 1536.9) than the model which included average of 24-h BP (Akaike Information Criterion = 1553.6). A higher hazard ratio (HR) was observed for non-dipping [HR 2.22; 95% confidence interval (CI): 1.55–3.17; P &lt; 0.0001] and for high BP variability (HR 1.84; 95% CI: 1.26–2.65; P = 0.0015) than for high average 24-h BP (HR 1.58; 95% CI: 1.07–2.33; P = 0.020). When average 24-h ambulatory BP was included in a nested model, the −2log likelihood decreased from 1524.9 to 1519.3, and there was a tendency for an interactive effect between 24-h BP and non-dipping on risk of cardiovascular events (P = 0.092).

Conclusion
In young hypertensive individuals, prognostic models including BP variability and non-dipping pattern provide better information than models with average 24-h ambulatory BP alone. More consideration should be given to BP variability and the day-night BP pattern beyond the average 24-h ambulatory BP in young hypertensive subjects.
Epicardial fat and atrial fibrillation: the perils of atrial failure
Authors: Poggi Andrea Lorenzo , Gaborit Bénédicte , Schindler Thomas Hellmut , Liberale Luca , Montecucco Fabrizio , Carbone Federico 
Published: January 2022

Abstract
Obesity is a heterogeneous condition, characterized by different phenotypes and for which the classical assessment with body mass index may underestimate the real impact on cardiovascular (CV) disease burden. An epidemiological link between obesity and atrial fibrillation (AF) has been clearly demonstrated and becomes even more tight when ectopic (i.e. epicardial) fat deposition is considered. Due to anatomical and functional features, a tight paracrine cross-talk exists between epicardial adipose tissue (EAT) and myocardium, including the left atrium (LA). Alongside—and even without—mechanical atrial stretch, the dysfunctional EAT may determine a pro-inflammatory environment in the surrounding myocardial tissue. This evidence has provided a new intriguing pathophysiological link with AF, which in turn is no longer considered a single entity but rather the final stage of atrial remodelling. This maladaptive process would indeed include structural, electric, and autonomic derangement that ultimately leads to overt disease. Here, we update how dysfunctional EAT would orchestrate LA remodelling. Maladaptive changes sustained by dysfunctional EAT are driven by a pro-inflammatory and pro-fibrotic secretome that alters the sinoatrial microenvironment. Structural (e.g. fibro-fatty infiltration) and cellular (e.g. mitochondrial uncoupling, sarcoplasmic reticulum fragmentation, and cellular protein quantity/localization) changes then determine an electrophysiological remodelling that also involves the autonomic nervous system. Finally, we summarize how EAT dysfunction may fit with the standard guidelines for AF. Lastly, we focus on the potential benefit of weight loss and different classes of CV drugs on EAT dysfunction, LA remodelling, and ultimately AF onset and recurrence.
A ribosomal operon database and MegaBLAST settings for strain-level resolution of microbiomes
Authors: Kerkhof Lee J , Roth Pierce A , Deshpande Samir V , Bernhards R Cory , Liem Alvin T , Hill Jessica M , Häggblom Max M , Webster Nicole S , Ibironke Olufunmilola , Mirzoyan Seda , Polashock James J , Sullivan Raymond F 
Published: January 2022

AbstractCurrent methods to characterize microbial communities generally employ sequencing of the 16S rRNA gene (&lt;500 bp) with high accuracy (∼99%) but limited phylogenetic resolution. However, long-read sequencing now allows for the profiling of near-full-length ribosomal operons (16S-ITS-23S rRNA genes) on platforms such as the Oxford Nanopore MinION. Here, we describe an rRNA operon database with &gt;300 ,000 entries, representing &gt;10 ,000 prokaryotic species and ∼ 150, 000 strains. Additionally, BLAST parameters were identified for strain-level resolution using in silico mutated, mock rRNA operon sequences (70–95% identity) from four bacterial phyla and two members of the Euryarchaeota, mimicking MinION reads. MegaBLAST settings were determined that required &lt;3 s per read on a Mac Mini with strain-level resolution for sequences with &gt;84% identity. These settings were tested on rRNA operon libraries from the human respiratory tract, farm/forest soils and marine sponges ( n = 1, 322, 818 reads for all sample sets). Most rRNA operon reads in this data set yielded best BLAST hits (95 ± 8%). However, only 38–82% of library reads were compatible with strain-level resolution, reflecting the dominance of human/biomedical-associated prokaryotic entries in the database. Since the MinION and the Mac Mini are both portable, this study demonstrates the possibility of rapid strain-level microbiome analysis in the field.
Genome-scale modeling of yeast metabolism: retrospectives and perspectives
Authors: Chen Yu , Li Feiran , Nielsen Jens 
Published: January 2022

Abstract
Yeasts have been widely used for production of bread, beer and wine, as well as for production of bioethanol, but they have also been designed as cell factories to produce various chemicals, advanced biofuels and recombinant proteins. To systematically understand and rationally engineer yeast metabolism, genome-scale metabolic models (GEMs) have been reconstructed for the model yeast Saccharomyces cerevisiae and nonconventional yeasts. Here, we review the historical development of yeast GEMs together with their recent applications, including metabolic flux prediction, cell factory design, culture condition optimization and multi-yeast comparative analysis. Furthermore, we present an emerging effort, namely the integration of proteome constraints into yeast GEMs, resulting in models with improved performance. At last, we discuss challenges and perspectives on the development of yeast GEMs and the integration of proteome constraints.
ATP Synthase K+- and H+-fluxes Drive ATP Synthesis and Enable Mitochondrial K+-“Uniporter” Function: II. Ion and ATP Synthase Flux Regulation
Authors: Juhaszova Magdalena , Kobrinsky Evgeny , Zorov Dmitry B , Nuss H Bradley , Yaniv Yael , Fishbein Kenneth W , de Cabo Rafael , Montoliu Lluis , Gabelli Sandra B , Aon Miguel A , Cortassa Sonia , Sollott Steven J 
Published: January 2022

AbstractWe demonstrated that ATP synthase serves the functions of a primary mitochondrial K+ “uniporter,” i.e., the primary way for K+ to enter mitochondria. This K+ entry is proportional to ATP synthesis, regulating matrix volume and energy supply-vs-demand matching. We show that ATP synthase can be upregulated by endogenous survival-related proteins via IF1. We identified a conserved BH3-like domain of IF1 which overlaps its “minimal inhibitory domain” that binds to the β-subunit of F1. Bcl-xL and Mcl-1 possess a BH3-binding-groove that can engage IF1 and exert effects, requiring this interaction, comparable to diazoxide to augment ATP synthase's H+ and K+ flux and ATP synthesis. Bcl-xL and Mcl-1, but not Bcl-2, serve as endogenous regulatory ligands of ATP synthase via interaction with IF1 at this BH3-like domain, to increase its chemo-mechanical efficiency, enabling its function as the recruitable mitochondrial KATP-channel that can limit ischemia-reperfusion injury. Using Bayesian phylogenetic analysis to examine potential bacterial IF1-progenitors, we found that IF1 is likely an ancient (∼2 Gya) Bcl-family member that evolved from primordial bacteria resident in eukaryotes, corresponding to their putative emergence as symbiotic mitochondria, and functioning to prevent their parasitic ATP consumption inside the host cell.
Chromosome-Scale Genome Assembly of Gilia yorkii Enables Genetic Mapping of Floral Traits in an Interspecies Cross
Authors: Jarvis David E , Maughan Peter J , DeTemple Joseph , Mosquera Veronica , Li Zheng , Barker Michael S , Johnson Leigh A , Whipple Clinton J 
Published: January 2022

Abstract
Substantial morphological variation in land plants remains inaccessible to genetic analysis because current models lack variation in important ecological and agronomic traits. The genus Gilia was historically a model for biosystematics studies and includes variation in morphological traits that are poorly understood at the genetic level. We assembled a chromosome-scale reference genome of G. yorkii and used it to investigate genome evolution in the Polemoniaceae. We performed QTL (quantitative trait loci) mapping in a G. yorkii×G. capitata interspecific population for traits related to inflorescence architecture and flower color. The genome assembly spans 2.75 Gb of the estimated 2.80-Gb genome, with 96.7% of the sequence contained in the nine largest chromosome-scale scaffolds matching the haploid chromosome number. Gilia yorkii experienced at least one round of whole-genome duplication shared with other Polemoniaceae after the eudicot paleohexaploidization event. We identified QTL linked to variation in inflorescence architecture and petal color, including a candidate for the major flower color QTL—a tandem duplication of flavanol 3′,5′-hydroxylase. Our results demonstrate the utility of Gilia as a forward genetic model for dissecting the evolution of development in plants including the causal loci underlying inflorescence architecture transitions.
Hostility Toward Baby Boomers on TikTok
Authors: Ng Reuben , Indran Nicole 
Published: January 2022

Abstract

Background and Objectives
The recent entry of the hashtag #OkBoomer into social media vernacular underscores the collective frustration of younger people with a group whose views they find increasingly incompatible with theirs. Most social media analyses in gerontology focus on the content on Twitter and Facebook, with content on TikTok virtually unexplored. Given the burgeoning popularity of TikTok among younger people, we assess the content of TikTok videos with the hashtags #OkBoomer or #Boomer to distill the undercurrents of hostility expressed by younger people toward Baby Boomers.

Research Design and Methods
We collated TikTok videos (N = 332) with the hashtags #OkBoomer or #Boomer, which received over 5.4 billion views. Both inductive and deductive approaches guided the qualitative content analysis of the videos.

Results
Five themes emerged. Most videos (79%) described “Negative Encounters with Baby Boomers” (Theme 1); 58% were about “Conflicting Values/Beliefs between Baby Boomers and Younger People” (Theme 2); 39% were about “Baby Boomers Antagonizing Younger Generations” (Theme 3); 22% of the videos made references to the “Karen Meme” (Theme 4); and 7% bemoaned the existence of a “Wealth Gap” between Baby Boomers and younger people (Theme 5).

Discussion and Implications
Findings reveal that the usage of the hashtags #OkBoomer and #Boomer is highly nuanced, at times explicitly ageist, and at others, emblematic of a phenomenon far more complex than ageism. There is a need to leverage social media as a space to foster interaction between older and younger people. Society is ultimately well served by intergenerational interaction.
A Guide to Inverse Kinematic Marker-Guided Rotoscoping Using IK Solvers
Authors: Wiseman Ashleigh L A , Demuth Oliver E , Hutchinson John R 
Published: January 2022

SynopsisX-ray Reconstruction of Moving Morphology (XROMM) permits researchers to see beneath the skin, usually to see musculoskeletal movements. These movements can be tracked and later used to provide information regarding the mechanics of movement. Here, we discuss “IK marker-guided rotoscoping”—a method that combines inverse kinematic solvers with that of traditional scientific rotoscoping methods to quickly and efficiently overlay 3D bone geometries with the X-ray shadows from XROMM data. We use a case study of three Nile crocodiles’ (Crocodylus niloticus) forelimbs and hindlimbs to evaluate this method. Within these limbs, different marker configurations were used: some configurations had six markers, others had five markers, and all forelimb data only had three markers. To evaluate IK marker-guided rotoscoping, we systematically remove markers in the six-marker configuration and then test the magnitudes of deviation in translations and rotations of the rigged setup with fewer markers versus those of the six-marker configuration. We establish that IK marker-guided rotoscoping is a suitable method for “salvaging” data that may have too few markers.
Oral levofloxacin: population pharmacokinetics model and pharmacodynamics study in bone and joint infections
Authors: Canouï Etienne , Kerneis Solen , Morand Philippe , Enser Maya , Gauzit Rémy , Eyrolle Luc , Leclerc Philippe , Contejean Adrien , Zheng Yi , Anract Philippe , Hirt Deborah , Treluyer Jean Marc , Bouazza Naim , Benaboud Sihem 
Published: January 2022

Abstract

Objectives
This study aimed at characterizing the pharmacokinetics (PK) of oral levofloxacin in adult patients in order to optimize dosing scheme and explore the PK/pharmacodynamics (PD) of levofloxacin in bone and joint infections (BJIs).

Methods
From November 2015 to December 2019, all patients hospitalized in Cochin Hospital, treated with levofloxacin and who had at least one dosage for therapeutic drug monitoring were included. PK was described using non-linear mixed-effect modelling. In a subgroup of patients with BJIs, the association between PK, MIC for the isolated pathogen and clinical outcome was investigated. Monte Carlo simulations investigated dosing regimens to achieve the PK/PD target (AUC/MIC ratio &gt;100).

Results
One hundred and two patients were included (199 measurements), including 32 treated for BJI. A one-compartment model with first-order absorption and elimination best described the data. Effects of estimated creatinine clearance (eCLCR) and age were significant on levofloxacin clearance. In BJI patients, no significant association was found between levofloxacin PK/microbiological parameters and either clinical outcome or adverse events. Based on our model, we proposed optimized oral levofloxacin dosing regimens according to renal function, to reach the PK/PD target AUC/MIC ratio &gt;100 for three frequent causative pathogens (Staphylococcus aureus, Enterobacterales and Pseudomonas aeruginosa).

Conclusions
Our results reinforce the need of determining the MIC and using therapeutic drug monitoring in complex infections caused by P. aeruginosa.
Partial oral antibiotic treatment of endocarditis in patients who inject drugs: a case series
Authors: Miller Kaylie , Evans Emily , Sheridan Kathleen R. , Nauriyal Varidhi , Viehman J. Alexander , Rivosecchi Ryan , Stoner Bobbi Jo , El-Dalati Sami 
Published: January 2022

Abstract

Background
Recent literature has demonstrated that partial oral antibiotic treatment of infectious endocarditis is non-inferior to IV therapy in select patients. Despite the rising incidence of injection drug use-related endocarditis, partial oral therapy has not been well studied in persons who inject drugs.

Objectives
To evaluate the rate of relapsed infection and 90 day mortality in patients with infectious endocarditis treated with partial oral antibiotic therapy.

Methods
Consecutive patients with infectious endocarditis treated with partial oral antibiotic therapy were identified by study investigators and reviewed by independent clinicians. The decision to use partial oral antibiotic therapy was made by the institution’s multidisciplinary endocarditis team.

Results
In 11 cases of infective endocarditis treated with partial oral antibiotic therapy, 9 of which were complicated by injection drug use, there were no relapsed infections with the primary organism. Five patients underwent surgical valve replacement, and the median duration of oral antibiotic therapy was 23 days. All patients survived to in-hospital discharge and 90 days post-discharge. Ten patients followed up with an infectious diseases provider after discharge.

Conclusions
These data add to existing literature demonstrating non-inferior outcomes with partial oral antibiotic treatment when compared with IV antibiotic treatment alone in patients with endocarditis, including persons who inject drugs.
A systematic review of the impacts of oral tetracycline class antibiotics on antimicrobial resistance in normal human flora
Authors: Truong Robinson , Tang Vincent , Grennan Troy , Tan Darrell H. S. 
Published: January 2022

Abstract

Objectives
There is interest in doxycycline as prophylaxis against sexually transmitted infections (STIs), but concern about antimicrobial resistance (AMR). We conducted a systematic review (CRD42021273301) of the impact of oral tetracycline-class antibiotics on AMR in normal flora.

Methods
We searched MEDLINE, EMBASE, the Cochrane Library (1940–2021) and conference proceedings (2014–21) for randomized controlled trials in adults comparing daily oral tetracycline-class antibiotics to non-tetracycline controls. The primary outcome was AMR to tetracyclines; secondary outcomes included resistance to non-tetracyclines. Data were inappropriate for meta-analysis, so we analysed findings descriptively.

Results
Our search yielded 6265 abstracts of which 7 articles fulfilled inclusion criteria. Most were at moderate/high risk of bias, generally due to inadequate methodologic reporting. Studies used doxycycline, tetracycline, oxytetracycline or minocycline for 2–18 weeks. Most observed an increased burden of tetracycline resistance, including in subgingival (n = 3 studies), gastrointestinal (n = 2) and upper respiratory tract (n = 1) flora; one study of skin flora found no change in tetracycline-resistant Propionibacterium species after 18 weeks of oxytetracycline/minocycline. Four studies reassessed AMR at 2–50 weeks post-intervention and reported varying degrees of resistance. Three articles reported on the prevalence of non-tetracycline AMR after doxycycline prophylaxis, of which one found a transient increase among gastrointestinal Escherichia coli; the other two showed no difference from control.

Conclusions
Although the effects are modest and transient, limited data from small prospective studies may suggest that oral tetracyclines for 2–18 weeks increase resistance in subgingival, gastrointestinal and upper respiratory tract flora. STI prophylaxis trials should include AMR in commensal bacteria as study outcomes.