bluuebunny/crossref_metadata_2025 huggingface dataset:
Telepharmacy services in acute care: Diverse needs within a large health system
Authors: Kester Kenneth A , Finck Karen M , Reehal Praveen , Reynolds Dorraine
Published: January 2022

Purpose

In this paper, we describe CommonSpirit Health’s telepharmacy service, which serves 64 hospitals in 10 states. Hospitals range in size from critical access to quaternary care centers.

Telepharmacy services in acute care may be divided into 2 primary styles: hospitals requiring after-hours support utilizing telepharmacists to bridge shifts otherwise uncovered by pharmacists and hospitals with round-the-clock onsite pharmacy services utilizing telepharmacists to enhance efficiency in processing medication orders. When providing after-hours service, telepharmacists review all medication orders. The primary goal is to provide pharmacist care at all hours. In hospitals with round-the-clock onsite pharmacy services, telepharmacists focus on efficiency of medication order review. Median turnaround times in these hospitals decreased 50% to 70% after implementing a telepharmacy service. Barriers to implementation include managing different electronic health records, variability in hospital practices, and communicating with onsite clinicians. Regular interaction with onsite leaders is a key component in overcoming these barriers. This enables the telepharmacy team to respond to hospital-specific changes and maintain competence. The service adjusts to provide additional support based on the needs of the sites. Most telepharmacists work from home. While this can present challenges, we consider it an advantage in recruitment and retention.

Conclusion

CommonSpirit Health utilizes its telepharmacy service for hospitals large and small to enhance efficiency in processing medication orders and to provide round-the-clock pharmacist care.
Rethinking Masculinities Studies
Authors: Breu Christopher
Published: January 2022

This review essay examines three new books in masculinities studies. It also provides a mapping of the field as it has changed over the past twenty years, exploring how our understanding of masculinity has changed with recent developments in trans, intersex, and queer theory and activism. How does the field change in response to changing conceptions of gender in the present? The review provides a provisional answer to this question.

Three recent books on masculinity in US culture provide an opportunity to examine how much the field of masculinities studies has kept up with changing frameworks around gender and embodiment in the present.
ABlooper: fast accurate antibody CDR loop structure prediction with accuracy estimation
Authors: Abanades Brennan , Georges Guy , Bujotzek Alexander , Deane Charlotte M
Published: January 2022

Motivation

Antibodies are a key component of the immune system and have been extensively used as biotherapeutics. Accurate knowledge of their structure is central to understanding their antigen-binding function. The key area for antigen binding and the main area of structural variation in antibodies are concentrated in the six complementarity determining regions (CDRs), with the most important for binding and most variable being the CDR-H3 loop. The sequence and structural variability of CDR-H3 make it particularly challenging to model. Recently deep learning methods have offered a step change in our ability to predict protein structures.

Results

In this work, we present ABlooper, an end-to-end equivariant deep learning-based CDR loop structure prediction tool. ABlooper rapidly predicts the structure of CDR loops with high accuracy and provides a confidence estimate for each of its predictions. On the models of the Rosetta Antibody Benchmark, ABlooper makes predictions with an average CDR-H3 RMSD of 2.49 Å, which drops to 2.05 Å when considering only its 75% most confident predictions.

Availability and implementation

https://github.com/oxpig/ABlooper.

Supplementary information

Supplementary data are available at Bioinformatics online.
EDTox: an R Shiny application to predict the endocrine disruption potential of compounds
Authors: Sakhteman Amirhossein , Ghosh Arindam , Fortino Vittorio
Published: January 2022

Purpose

Endocrine disruptors are a rising concern due to the wide array of health issues that it can cause. Although there are tools for mode of action (MoA)-based prediction of endocrine disruption (e.g. QSAR Toolbox and iSafeRat), none of them is based on toxicogenomics data. Here, we present EDTox, an R Shiny application enabling users to explore and use a computational method that we have recently published to identify and prioritize endocrine disrupting (ED) chemicals based on toxicogenomic data. The EDTox pipeline utilizes previously trained toxicogenomic-driven classifiers to make predictions on new untested compounds by using their molecular initiating events. Furthermore, the proposed R Shiny app allows users to extend the prediction systems by training and adding new classifiers based on new available toxicogenomic data. This functionality helps users to explore the ED potential of chemicals in new, untested exposure scenarios.

Availability and implementation

This tool is available as web application (www.edtox.fi) and stand-alone software on GitHub and Zenodo (https://doi.org/10.5281/zenodo.5817093).

Supplementary information

Supplementary data are available at Bioinformatics online.
DeepUMQA: ultrafast shape recognition-based protein model quality assessment using deep learning
Authors: Guo Sai-Sai , Liu Jun , Zhou Xiao-Gen , Zhang Gui-Jun
Published: January 2022

Motivation

Protein model quality assessment is a key component of protein structure prediction. In recent research, the voxelization feature was used to characterize the local structural information of residues, but it may be insufficient for describing residue-level topological information. Design features that can further reflect residue-level topology when combined with deep learning methods are therefore crucial to improve the performance of model quality assessment.

Results

We developed a deep-learning method, DeepUMQA, based on Ultrafast Shape Recognition (USR) for the residue-level single-model quality assessment. In the framework of the deep residual neural network, the residue-level USR feature was introduced to describe the topological relationship between the residue and overall structure by calculating the first moment of a set of residue distance sets and then combined with 1D, 2D and voxelization features to assess the quality of the model. Experimental results on the CASP13, CASP14 test datasets and CAMEO blind test show that USR could supplement the voxelization features to comprehensively characterize residue structure information and significantly improve model assessment accuracy. The performance of DeepUMQA ranks among the top during the state-of-the-art single-model quality assessment methods, including ProQ2, ProQ3, ProQ3D, Ornate, VoroMQA, ProteinGCN, ResNetQA, QDeep, GraphQA, ModFOLD6, ModFOLD7, ModFOLD8, QMEAN3, QMEANDisCo3 and DeepAccNet.

Availability and implementation

The DeepUMQA server is freely available at http://zhanglab-bioinf.com/DeepUMQA/.

Supplementary information

Supplementary data are available at Bioinformatics online.
fastANCOM: a fast method for analysis of compositions of microbiomes
Authors: Zhou Chao , Wang Huimin , Zhao Hongyu , Wang Tao
Published: January 2022

Analysis of compositions of microbiomes (ANCOM) compares the absolute abundances of microbes between two or more ecosystems using relative abundances in specimens derived from these ecosystems. Despite its impressive performance, there are two drawbacks to ANCOM. First, with K microbes it requires fitting K(K−1)/2 models for log-ratios of counts, and so can be computationally intensive. Second, it does not output P-values for microbes detected as differentially abundant. We propose a fast implementation of ANCOM, fastANCOM, that fits only K models for log-transformed counts. fastANCOM provides P-values to declare statistical significance and outputs log fold changes of abundance between groups. We demonstrate that fastANCOM compares favorably with existing differential abundance testing methods in terms of running time, false discovery rate and power.

Availability and implementation

fastANCOM is available at https://github.com/ZRChao/fastANCOM.

Supplementary information

Supplementary data are available at Bioinformatics online.
CELSR2, a new player in motor neuron axon growth and regeneration
Authors: Petrova Veselina , Hakim Sara
Published: January 2022

This scientific commentary refers to ‘Inactivating Celsr2 promotes motor axon fasciculation and regeneration in mouse and human’ by Wen et al. (https://doi.org/10.1093/brain/awab317).
Abnormal neurite density and orientation dispersion in frontal lobe link to elevated hyperactive/impulsive behaviours in young adults with traumatic brain injury
Authors: Cao Meng , Luo Yuyang , Wu Ziyan , Wu Kai , Li Xiaobo
Published: January 2022

Traumatic brain injury is a major public health concern. A significant proportion of individuals experience post-traumatic brain injury behavioural impairments, especially in attention and inhibitory control domains. Traditional diffusion-weighted MRI techniques, such as diffusion tensor imaging, have provided tools to assess white matter structural disruptions reflecting the long-term brain tissue alterations associated with traumatic brain injury. The recently developed neurite orientation dispersion and density imaging is a more advanced diffusion MRI modality, which provides more refined characterization of brain tissue microstructures by assessing the neurite orientation dispersion and neurite density properties. In this study, neurite orientation dispersion and density imaging data from 44 young adults with chronic traumatic brain injury (who had no prior-injury diagnoses of any sub-presentation of attention deficits/hyperactivity disorder or experience of severe inattentive and/or hyperactive behaviours) and 45 group-matched normal controls were investigated, to assess the post-injury morphometrical and microstructural brain alterations and their relationships with the behavioural outcomes. Maps of fractional anisotropy, neurite orientation dispersion index and neurite density index were calculated. Vertex-wise and voxel-wise analyses were conducted for grey matter and white matter, respectively. Post hoc region-of-interest-based analyses were also performed. Compared to the controls, the group of traumatic brain injury showed significantly increased orientation dispersion index and significantly decreased neurite density index in various grey matter regions, as well as significantly decreased orientation dispersion index in several white matter regions. Brain–behavioural association analyses indicated that the reduced neurite density index of the left precentral gyrus and the reduced orientation dispersion index of the left superior longitudinal fasciculus were significantly associated with elevated hyperactive/impulsive symptoms in the patients with traumatic brain injury. These findings suggest that post-injury chronical neurite intracellular volume and angular distribution anomalies in the frontal lobe, practically the precentral area, can significantly contribute to the onset of hyperactive/impulsive behaviours in young adults with traumatic brain injury.
Mucosal-associated invariant T cells are activated in an interleukin-18-dependent manner in Epstein–Barr virus-associated T/natural killer cell lymphoproliferative diseases
Authors: Ishikawa Yuriko , Yamada Masaki , Wada Naomi , Takahashi Etsuko , Imadome Ken-Ichi
Published: January 2022

Mucosal-associated invariant T (MAIT) cells are a type of innate immune cells that protect against some infections. However, the involvement of MAIT cells in Epstein–Barr virus-associated T/natural killer cell lymphoproliferative diseases (EBV-T/NK-LPD) is unclear. In this study, we found that MAIT cells were highly activated in the blood of patients with EBV-T/NK-LPD. MAIT cell activation levels correlated with disease severity and plasma IL-18 levels. Stimulation of healthy peripheral blood mononuclear cells with EBV resulted in activation of MAIT cells, and this activation level was enhanced by exogenous IL-18. MAIT cells stimulated by IL-18 might thus be involved in the immunopathogenesis of EBV-T/NK-LPD.
Intrinsic dynamics and topography of sensory input systems
Authors: Çatal Yasir , Gomez-Pilar Javier , Northoff Georg
Published: January 2022

The brain is continuously bombarded by external stimuli, which are processed in different input systems. The intrinsic features of these sensory input systems remain yet unclear. Investigating topography and dynamics of input systems is the goal of our study in order to better understand the intrinsic features that shape their neural processing. Using a functional magnetic resonance imaging dataset, we measured neural topography and dynamics of the input systems during rest and task states. Neural dynamics were probed by scale-free activity, measured with the power-law exponent (PLE), as well as by order/disorder as measured with sample entropy (SampEn). Our main findings during both rest and task states are: 1) differences in neural dynamics (PLE, SampEn) between regions within each of the three sensory input systems 2) differences in topography and dynamics among the three input systems; 3) PLE and SampEn correlate and, as demonstrated in simulation, show non-linear relationship in the critical range of PLE; 4) scale-free activity during rest mediates the transition of SampEn from rest to task as probed in a mediation model. We conclude that the sensory input systems are characterized by their intrinsic topographic and dynamic organization which, through scale-free activity, modulates their input processing.
Hyperexcitable and immature-like neuronal activity in the auditory cortex of adult rats lacking the language-linked CNTNAP2 gene
Authors: Scott Kaela E , Mann Rajkamalpreet S , Schormans Ashley L , Schmid Susanne , Allman Brian L
Published: January 2022

The contactin-associated protein-like 2 gene, CNTNAP2, is a highly penetrant risk gene thought to play a role in the genetic etiology of language-related disorders, such as autism spectrum disorder and developmental language disorder. Despite its candidacy for influencing language development, few preclinical studies have examined the role of CNTNAP2 in auditory processing. Using in vivo and in vitro electrophysiological recordings in a rat model with translational validity, we report that a loss of the Cntnap2 gene function caused immature-like cortical evoked potentials, delayed multiunit response latencies to acoustic stimuli, impaired temporal processing, and led to a pattern of hyperexcitability in both multiunit and single cell recordings in adulthood. These collective results provide direct evidence that a constitutive loss of Cntnap2 gene function in rats can cause auditory processing impairments similar to those seen in language-related human disorders, indicating that its contribution in maintaining cortical neuron excitability may underlie the cortical activity alterations observed in Cntnap2−/− rats.
Low-intensity focused ultrasound stimulation reverses social avoidance behavior in mice experiencing social defeat stress
Authors: Wang Yimeng , Bai Yang , Xiao Xi , Wang Ling , Wei Ganjiang , Guo Mingkun , Song Xizi , Tian Yutao , Ming Dong , Yang Jiajia , Zheng Chenguang
Published: January 2022

The excitatory neurons of the medial prefrontal cortex (mPFC) respond to social stimuli. However, little is known about how the neural activity is altered during social avoidance, and whether it could act as a target of low-intensity focused ultrasound stimulation (LIFUS) to rescue social deficits. The present study aimed to investigate the mechanisms of neuronal activities and inflammatory responses underlying the effect of LIFUS on social avoidance. We found that chronic LIFUS stimulation can effectively improve social avoidance in the defeated mice. Calcium imaging recordings by fiber photometry in the defeated mice showed inhibited ensemble activity during social behaviors. LIFUS instantaneously triggered the mPFC neuronal activities, and chronic LIFUS significantly enhanced their neuronal excitation related to social interactions. We further found that the excessive activation of microglial cells and the overexpression of the inflammation signaling, i.e. Toll-like receptors(TLR4)/nuclear factor-kappaB(NF-КB), in mPFC were significantly inhibited by LIFUS. These results suggest that the LIFUS may inhibit social avoidance behavior by reducing activation of the inflammatory response, increasing neuronal excitation, and protecting the integrity of the neuronal structure in the mPFC. Our findings raised the possibility of LIFUS being applied as novel neuromodulation for social avoidance treatment in neuropsychiatric diseases.
The convergence and divergence of episodic and semantic functions across lateral parietal cortex
Authors: Humphreys Gina F , Jung JeYoung , Lambon Ralph Matthew A
Published: January 2022

Decades of research have highlighted the importance of lateral parietal cortex (LPC) across a myriad of cognitive domains. Yet, the underlying function of LPC remains unclear. Two domains that have emphasized LPC involvement are semantic memory and episodic memory retrieval. From each domain, sophisticated functional models have been proposed, as well as the more domain-general assumption that LPC is engaged by any form of internally directed cognition (episodic/semantic retrieval being examples). Here we used a combination of functional magnetic resonance imaging, functional connectivity, and diffusion tensor imaging white-matter connectivity to show that (i) ventral LPC (angular gyrus [AG]) was positively engaged during episodic retrieval but disengaged during semantic memory retrieval and (ii) activity negatively varied with task difficulty in the semantic task whereas episodic activation was independent of difficulty. In contrast, dorsal LPC (intraparietal sulcus) showed domain general activation that was positively correlated with task difficulty. Finally, (iii) a dorsal–ventral and anterior–posterior gradient of functional and structural connectivity was found across the AG (e.g. mid-AG connected with episodic retrieval). We propose a unifying model in which LPC as a whole might share a common underlying neurocomputation (multimodal buffering) with variations in the emergent cognitive functions across subregions arising from differences in the underlying connectivity.
Modeling the Impact of Vaccination Strategies for Nursing Homes in the Context of Increased Severe Acute Respiratory Syndrome Coronavirus 2 Community Transmission and Variants
Authors: Holmdahl Inga , Kahn Rebecca , Slifka Kara Jacobs , Dooling Kathleen , Slayton Rachel B
Published: January 2022

Using an agent-based model, we examined the impact of community prevalence, the Delta variant, staff vaccination coverage, and booster vaccines for residents on outbreak dynamics in nursing homes. Increased staff coverage and high booster vaccine effectiveness leads to fewer infections, but cumulative incidence is highly dependent on community transmission.
Epidemiology of native kidney disease in Flanders: results from the FCGG kidney biopsy registry
Authors: Laurens Wim , Deleersnijder Dries , Dendooven Amélie , Lerut Evelyne , De Vriese An S , Dejagere Tom , Helbert Mark , Hellemans Rachel , Koshy Priyanka , Maes Bart , Pipeleers Lissa , Van Craenenbroeck Amaryllis H , Van Laecke Steven , Vande Walle Johan , Coutteneye Marie M , De Meester Johan , Sprangers Ben ,   The FCGG collaborative group, De Vriese An , De Rycke Anja , Bogaert Anne-Marie , Woestenburg Annemie , Denys Bart , Maes Bart , Peeters Domien , Vanbelleghem Hilde , Donck Jan , Scharpé Johan , De Clippeleir Nele , Vanparys Joris , Meyvis Karen , Vandepitte Kurt , Reyns Liza-Maria , Verresen Luc , Decupere Marc , Helbert Mark , Zeegers Miranda , Neirynck Nathalie , Bernaert Pascale , Dejagere Tom , Lemahieu Wim , Sprangers Ben , Pipeleers Lissa , Hellemans Rachel , Van Laecke Steven , Levtchenko Elena , Karamaria Sevasti , Van Hoeck Koen , Trouet Dominique , Mauel Reiner , Dendooven Amélie , Hoorens Anne , Van Dorpe Jo , Praet Marleen , Geers Caroline , Lerut Evelyne , Koshy Priyanka , Roskams Tania , Aydin Selda , Siozopoulou Vasiliki , Schelfhout Anne-Marie , De Raeve Hendrik , Steenkiste Edwin , Dedeurwaerdere Francesca , Dalle Ignace , Cokelaere Kristof , Deloose Stijn , De Paepe Pascale , Van Eyken Peter
Published: January 2022

Background

The Flemish Collaborative Glomerulonephritis Group (FCGG) registry is the first population-based native kidney biopsy registry in Flanders, Belgium. In this first analysis, we report on patient demographics, frequency distribution and incidence rate of biopsied kidney disease in adults in Flanders.

Methods

From January 2017 to December 2019, a total of 2054 adult first native kidney biopsies were included. A ‘double diagnostic coding’ strategy was used, in which every biopsy sample received a histopathological and final clinical diagnosis. Frequency distribution and incidence rate of both diagnoses were reported and compared with other European registries.

Results

The median age at biopsy was 61.1 years (interquartile range, 46.1–71.7); male patients were more prevalent (62.1%) and biopsy incidence rate was 129.3 per million persons per year. Immunoglobulin A nephropathy was the most frequently diagnosed kidney disease (355 biopsies, 17.3% of total) with a similar frequency as in previously published European registries. The frequency of tubulointerstitial nephritis (220 biopsies, 10.7%) and diabetic kidney disease (154 biopsies, 7.5%) was remarkably higher, which may be attributed to changes in disease incidence as well as biopsy practices. Discordances between histopathological and final clinical diagnoses were noted and indicate areas for improvement in diagnostic coding systems.

Conclusions

The FCGG registry, with its ‘double diagnostic coding’ strategy, provides useful population-based epidemiological data on a large Western European population and allows subgroup selection for future research.
The Role of Wind and Semiochemicals in Mediating Switching Behavior in the Southern Pine Beetle (Coleoptera: Curculionidae: Scolytinae)
Authors: Sullivan Brian T , Brownie Cavell
Published: January 2022

Aggressive bark beetles colonize and kill healthy conifers through pheromone-mediated mass aggregation. In several species, the focal point of aggregation moves progressively from mass-attacked ‘focus trees’ to adjacent, unattacked ‘recipient trees’, resulting in infestation growth. This process, termed ‘switching’, is hypothesized to be mediated in whole or in part by antiaggregation pheromones released by beetles as colonization intensifies on a focus tree. We tested this hypothesis with the southern pine beetle, Dendroctonus frontalis Zimmermann (Coleoptera: Curculionidae: Scolytinae), by using a windvane apparatus that maintained an unbaited, black, cylindrical trap (surrogate for a recipient tree) continuously 4 m downwind from an identical trap baited with synthetic aggregation attractant (surrogate for a focus tree). In two of three replicated trials, addition of pheromone components with antiaggregation activity, endo-brevicomin or verbenone, to the upwind trap caused a significant but small (<15%) increase in the proportion of beetles caught in the downwind trap. In one of two trials with endo-brevicomin, this shift was associated with a significant reduction in catches in the downwind trap and an overall reduction in catches of beetles by the trap pair. This suggests that an inhibitor-induced increase in landings on the recipient relative to the focus tree may be countered by the radial effects of the inhibitor, which at sufficiently high release may reduce responses to both the focus and recipient tree. We discuss spatial factors that might govern the role of antiaggregation pheromones in stimulating infestation growth as well as additional factors that likely govern switching behavior.
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

Population 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

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

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 < 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

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

Current methods to characterize microbial communities generally employ sequencing of the 16S rRNA gene (<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 >300 ,000 entries, representing >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 <3 s per read on a Mac Mini with strain-level resolution for sequences with >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

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

We 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

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

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

Synopsis

X-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

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 >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 >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

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

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.