bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanistic Considerations and Pharmacokinetic Implications on Concomitant Drug Administration During CytoSorb Therapy
Authors: Scheier Joerg , Nelson Peter J. , Schneider Antoine , Colombier Sébastien , Kindgen-Milles Detlef , Deliargyris Efthymios N. , Nolin Thomas D. 
Published: May 2022

OBJECTIVE:
The CytoSorb hemoadsorption device (CytoSorbents Inc, Monmouth Junction, NJ) is increasingly used in many critical disease states. The potential impact on the pharmacokinetic (PK) of concomitantly administered drugs must be considered in clinical practice. The current review summarizes relevant mechanistic principles, available preclinical and clinical data, and provides general guidance for the management of concomitant drug administration during CytoSorb therapy.

DATA SOURCES:
Detailed search strategy using the PubMed and OVID MEDLINE databases, as well as presented congress abstracts for studies on drug removal by the CytoSorb device.

STUDY SELECTION:
Human, animal, and bench-top studies with PK or drug-removal data during CytoSorb therapy were selected for inclusion. Publications reporting on CytoSorb treatments for drug overdose were not considered.

DATA EXTRACTION:
Relevant PK data were examined and synthesized for narrative review.

DATA SYNTHESIS:
To date, PK data during CytoSorb hemoadsorption are available for more than 50 drugs, including analgesics, antiarrhythmics, anticonvulsants, antidepressants, antihypertensives, antiinfectives, antithrombotics, anxiolytics, and immunosuppressants. Based on available PK data, drugs were categorized into low (<30%), moderate (30–60%), or high rates of removal (>60%), or, alternatively, according to clearance increase relative to endogenous clearance: negligible (<25%), low (25–100%), moderate (100–400%), or high (>400%). In most reports, additional impact of the extracorporeal platform where CytoSorb was integrated was not available. Based on available data and considering drug, patient, and setup-specific aspects, general dosing guidance for clinical practice was developed.

CONCLUSIONS:
CytoSorb therapy may increase drug elimination through active removal. However, the extent of removal is heterogeneous, and its clinical significance, if any, depends on the broader clinical context, including a patient’s specific endogenous drug clearance and the underlying extracorporeal platform used. The available data, although not definitive, allow for general guidance on dosing adjustments during CytoSorb therapy; however, any treatment decisions should always be complemented by clinical judgment and therapeutic drug monitoring, when available.
Elderly Runners and Osteoarthritis: A Systematic Review
Authors: Migliorini Filippo , Marsilio Emanuela , Oliva Francesco , Hildebrand Frank , Maffulli Nicola 
Published: May 2022

Purpose:
The impact of running on the onset of osteoarthritis (OA) is controversial. This study compared the incidence of OA in elderly runners versus nonrunners.

Material and Methods:
This systematic review was conducted according to the PRISMA guidelines. PubMed, Google scholar, Embase, and Web of Science databases were accessed in January 2022. All the published clinical studies investigating OA onset in runners versus non-runners were considered. Studies reporting data on OA and participants in other sports were excluded. Only studies investigating patients with a mean age older than 55 years were considered. The methodological quality of the articles was evaluated using the Newcastle-Ottawa Scale (NOS).

Results:
Data from 3001 participants and 6674 joints were retrieved. The mean age was 59.4±2.7 years. The mean body mass index was 24.6±2.5 kg/m2. The 5 included articles (963 runners, 2038 nonrunners) did not report significant differences in runners compared with controls.

Conclusion:
Middle aged runners did not present greater imaging or clinical signs of OA compared with nonrunner controls. Running at elite or recreational level did not increase the rate of OA progression in individuals older than 50 years.
Geometric microcanonical theory of two-dimensional truncated Euler flows
Authors: van Kan A. , Alexakis A. , Brachet M. 
Published: May 2022

This paper presents a geometric microcanonical ensemble perspective on two-dimensional truncated Euler flows, which contain a finite number of (Fourier) modes and conserve energy and enstrophy. We explicitly perform phase space volume integrals over shells of constant energy and enstrophy. Two applications are considered. In the first part, we determine the average energy spectrum for highly condensed flow configurations and show that the result is consistent with Kraichnan’s canonical ensemble description, despite the fact that no thermodynamic limit is invoked. In the second part, we compute the probability density for the largest-scale mode of a free-slip flow in a square, which displays reversals. We test the results against numerical simulations of a minimal model and find excellent agreement with the microcanonical theory, unlike the canonical theory, which fails to describe the bimodal statistics.
This article is part of the theme issue ‘Mathematical problems in physical fluid dynamics (part 2)’.
Spontaneous symmetry breaking for extreme vorticity and strain in the three-dimensional Navier–Stokes equations
Authors: Schorlepp Timo , Grafke Tobias , May Sandra , Grauer Rainer 
Published: May 2022

We investigate the spatio-temporal structure of the most likely configurations realizing extremely high vorticity or strain in the stochastically forced three-dimensional incompressible Navier–Stokes equations. Most likely configurations are computed by numerically finding the highest probability velocity field realizing an extreme constraint as solution of a large optimization problem. High-vorticity configurations are identified as pinched vortex filaments with swirl, while high-strain configurations correspond to counter-rotating vortex rings. We additionally observe that the most likely configurations for vorticity and strain spontaneously break their rotational symmetry for extremely high observable values. Instanton calculus and large deviation theory allow us to show that these maximum likelihood realizations determine the tail probabilities of the observed quantities. In particular, we are able to demonstrate that artificially enforcing rotational symmetry for large strain configurations leads to a severe underestimate of their probability, as it is dominated in likelihood by an exponentially more likely symmetry-broken vortex-sheet configuration.
This article is part of the theme issue ‘Mathematical problems in physical fluid dynamics (part 2)’.
Editorial: Mathematical problems in physical fluid dynamics: part II
Authors: Goluskin D. , Protas B. , Thiffeault J.-L. 
Published: May 2022

Fluid dynamics is a research area lying at the crossroads of physics and applied mathematics with an ever-expanding range of applications in natural sciences and engineering. However, despite decades of concerted research efforts, this area abounds with many fundamental questions that still remain unanswered. At the heart of these problems often lie mathematical models, usually in the form of partial differential equations, and many of the open questions concern the validity of these models and what can be learned from them about the physical problems. In recent years, significant progress has been made on a number of open problems in this area, often using approaches that transcend traditional discipline boundaries by combining modern methods of modelling, computation and mathematical analysis. The two-part theme issue aims to represent the breadth of these approaches, focusing on problems that are mathematical in nature but help to understand aspects of real physical importance such as fluid dynamical stability, transport, mixing, dissipation and vortex dynamics.
This article is part of the theme issue ‘Mathematical problems in physical fluid dynamics (part 2)’.
Assessment of Alzheimer-related Pathologies of Dementia Using Machine Learning Feature Selection
Authors: Rajab Mohammed D , Jammeh Emmanuel , Taketa Teruka , Brayne Carol , Matthews Fiona E , Su Li , Ince Paul G , Wharton Stephen B , Wang Dennis 
Published: May 2022

AbstractAlthough a variety of brain lesions may contribute to the pathological diagnosis of dementia, the relationship of these lesions to dementia, how they interact and how to quantify them remain uncertain. Systematically assessing neuropathological measures in relation to the cognitive and functional definitions of dementia may enable the development of better diagnostic systems and treatment targets. The objective of this study is to apply machine learning approaches for feature selection to identify key features of Alzheimer-related pathologies associated with dementia. We applied machine learning techniques for feature ranking and classification as an unbiased comparison of neuropathological features and assessment of their diagnostic performance using a cohort (n=186) from the Cognitive Function and Ageing Study (CFAS). Seven feature ranking methods using different information criteria consistently ranked 22 out of the 34 neuropathology features for importance to dementia classification. Braak neurofibrillary tangle stage, Beta-amyloid and cerebral amyloid angiopathy features were the most highly ranked, although were highly correlated with each other. The best performing dementia classifier using the top eight ranked neuropathology features achieved 79% sensitivity, 69% specificity, and 75% precision. A substantial proportion (40.4%) of dementia cases was consistently misclassified by all seven algorithms and any combination of the 22 ranked features. These results highlight the potential of using machine learning to identify key indices of plaque, tangle and cerebral amyloid angiopathy burdens that may be useful for the classification of dementia.
Longitudinal analyses of depression and anxiety highlight greater prevalence during COVID-19 lockdowns in the Dutch general population and a continuing increase in suicidal ideation in young adults
Authors: Ori Anil P. S. , Wieling Martijn ,   Lifelines Corona Research Initiative, van Loo Hanna M. 
Published: May 2022

AbstractObjectiveThe pandemic of the coronavirus disease 2019 (COVID-19) has led to an increased burden on mental health. This study therefore investigated the development of major depressive disorder (MDD), generalized anxiety disorder (GAD), and suicidal ideation in the Netherlands during the first fifteen months of the pandemic and three nation-wide lockdowns.MethodsParticipants of the Lifelines Cohort Study –a Dutch population-based sample-reported current symptoms of MDD and GAD, including suicidal ideation, according to DSM-IV criteria using a digital structured questionnaire. Between March 2020 and June 2021, 36,106 participants (aged 18-96) filled out a total of 629,811 questionnaires across 23 time points. Trajectories over time were estimated using generalized additive models and analyzed in relation to age, sex, and lifetime history of MDD/GAD to identify groups at risk.ResultsWe found non-linear trajectories for MDD and GAD with a higher number of symptoms and prevalence rates during periods of lockdown. The point prevalence of MDD and GAD peaked during the third hard lockdown at 2.88% (95% CI: 2.71%–3.06%) and 2.92% (95% CI: 2.76%-3.08%), respectively, in March 2021. Women, younger adults, and participants with a history of MDD/GAD reported significantly more symptoms. For suicidal ideation, we found a linear increase over time in younger participants which continued even after the lockdowns ended. For example, 4.63% (95% CI: 3.09%-6.96%) of 20-year-old participants reported suicidal ideation at our last measured time point in June 2021, which represents a 4.14x increase since the start of the pandemic.ConclusionsOur study showed greater prevalence of MDD and GAD during COVID-19 lockdowns suggesting that the pandemic and government enacted restrictions impacted mental health in the population. We furthermore found a continuing increase in suicidal ideation in young adults. This warrants for alertness in clinical practice and prioritization of mental health in public health policy.
Multi-ancestry genome-wide analysis identifies effector genes and druggable pathways for coronary artery calcification
Authors: Kavousi Maryam , Bos Maxime M. , Barnes Hanna J. , Lino Cardenas Christian L. , Wong Doris , O’Donnell Christopher J. , Bielak Lawrence F. , Peyser Patricia A. , Malhotra Rajeev , van der Laan Sander W. , Miller Clint L. 
Published: May 2022

AbstractCoronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts symptomatic coronary artery disease. Identifying genetic risk factors for CAC may point to new therapeutic avenues for preventing clinical disease. Here, we conducted a multi-ancestry genome-wide association study in 26,909 individuals of European ancestry and 8,867 individuals of African American ancestry. We identified 11 independent risk loci, of which 8 are novel for CAC. Some novel loci harbor candidate causal genes supported by multiple lines of functional evidence. Together, these findings help refine the genetic architecture of CAC, extend our understanding of the biological pathways underlying CAC formation, as well as identify druggable targets for CAC.
Assessment of Standard HIV Testing Services Delivery to Injured Persons Seeking Emergency Care in Nairobi, Kenya: A Prospective Observational Study
Authors: Aluisio Adam R. , Sugut Janet , Kinuthia John , Bosire Rose , Ochola Eric , Ngila Beatrice , Ojuka Daniel K. , Lee J. Austin , Maingi Alice , Guthrie Kate M. , Liu Tao , Mugambi Mary , Katz David A. , Farquhar Carey , Mello Michael J. 
Published: May 2022

AbstractEmergency departments (EDs) in Africa are contact points for key groups for HIV testing services (HTS) but understanding of ED-testing delivery is limited which may impeded program impacts. This study evaluated the offering and uptake of standard HTS among injured persons seeking ED care at Kenyatta National Hospital (KNH) in Nairobi, Kenya.An ED population of adult injured persons was prospectively enrolled (1 March - 25 May 2021) and followed through ED disposition. Participants requiring admission were followed through hospital discharge and willing participants were contacted at 28-days for follow up. Data on population characteristics and HTS were collected by personnel distinct from clinicians responsible for standard HTS. Descriptive analyses were performed and prevalence values with 95% confidence intervals (CI) were calculated for HIV parameters.The study enrolled 646 participants. The median age was 29 years with the majority male (87.8%). Most ED patients were discharged (58.9%). A prior HIV diagnosis was reported by 2.3% of participants and 52.7% reported their last testing as >6 months prior. Standard ED-HTS were offered to 49 or 8.6% of participants (95% CI: 5.8-9.9%), among which 89.8% accepted. For ED-tested participants 11.4% were newly diagnosed with HIV (95% CI: 5.0-24.0%). Among 243 participants admitted, testing was offered to 6.2% (95% CI: 3.9-9.9%), with 93.8% accepting. For admitted participants tested 13.3% (95% CI: 4.0-35.1%) were newly diagnosed (all distinct from ED cases). At 28-day follow up an additional 22 participants reported completing testing since ED visitation, with three newly diagnosed. During the full follow-up period the HIV prevalence in the population tested was 10.3% (95% CI: 5.3-19.0%); all being previously undiagnosed.Offering of standard HTS was infrequent, however, when offered, uptake and identification of new HIV diagnoses were high. These data suggest that opportunities exist to improve ED-HTS which could enhance identification of undiagnosed HIV.
Correlation of Suspected COVID-19 Symptoms with COVID-19 Positivity in Children
Authors: Satoskar Sanika A. , Hindman Daniel , Husain Amyna , Prichett Laura , Badaki Oluwakemi B. , Kane Ann 
Published: May 2022

AbstractBackgroundEarly in the pandemic, COVID-19 was found to infect adults at higher rates than children, leaving limited data on disease presentation in children. Further understanding of the epidemiology of COVID-19 symptoms among children is needed. Our aim was to explore how symptoms vary between children testing positive for COVID-19 infection versus children testing negative.MethodsData analysis of symptom prevalence among pediatric patients presenting to emergency departments (ED) in the Johns Hopkins Health System (JHHS) with concern for COVID-19 who subsequently received COVID-19 testing. Inclusion criteria included patients 0-17 years-of-age, ED evaluation between March 15th, 2020 - May 11th, 2020, and those who were ordered for COVID-19 testing. Chart review was performed to document symptoms using ED provider notes. Comparisons were made using chi-squared t-tests and Student’s t-tests.ResultsFever (62.6%) and cough (47.9%) were the most prevalent symptoms among children with suspected COVID-19 infection. Compared to children with a negative COVID-19 test, children who tested positive had higher prevalence of myalgia (21.7% vs 6.0%) and loss of taste/smell (15.2% vs 0.9%). Over half of the children who tested positive for COVID-19 had public insurance (52.2%) and 58.7% of the positive tests occurred among children with Hispanic ethnicity.ConclusionsMyalgia and loss of taste/smell were found to be significantly more prevalent among COVID-19 positive children compared to children testing negative. Additionally, children with public insurance and those with Hispanic ethnicity were more likely to test positive, emphasizing the importance of social factors in the screening and decision-making process.
Dog Size and Patterns of Disease History Across the Canine Age Spectrum: Results from the Dog Aging Project
Authors: Nam Yunbi , White Michelle , Karlsson Elinor K. , Creevy Kate E. , Promislow Daniel , McClelland Robyn L. ,   The Dog Aging Project Consortium
Published: May 2022

AbstractAge in dogs is associated with the risk of many diseases, and canine size is a major factor in that risk. However, the size effect is not as simple as the age effect. While small size dogs tend to live longer, some diseases are more prevalent among small dogs. Utilizing owner-reported data on disease history from a substantial number of companion dogs, we investigate how body size, as measured by weight, associates with the prevalence of a reported condition and its pattern across age for various disease categories. We found significant positive associations between weight and prevalence of skin, bone/orthopedic, gastrointestinal, ear/nose/throat, cancer/tumor, brain/neurologic, endocrine, and infectious diseases. Similarly, weight was negatively associated with the prevalence of eye, cardiac, liver/pancreas, and respiratory disease categories. Kidney/urinary disease prevalence did not vary by weight. We also found that the association between age and disease prevalence varied by dog size for many conditions including eye, cardiac, orthopedic, ear/nose/throat, and cancer. Controlling for sex, purebred/mixed breed, and geographic region made little difference in all disease categories we studied. Our results align with the reduced lifespan in larger dogs for most of the disease categories but suggest potential avenues for further examination.
Biochemical Characterization of a Fungal Bifunctional Type I Diterpene Synthase Brings a Cryptic Natural Product to Light
Authors: Zhang Peng , Wu Guangwei , Heard Stephanie C. , Niu Changshan , Bell Stephen A. , Li Fengli , Ye Ying , Zhang Yonghui , Winter Jaclyn M. 
Published: May 2022

AbstractWe report the identification of the tnd biosynthetic cluster from the marine-derived fungal strain Aspergillus flavipes CNL-338 and in vivo characterization of a cryptic type I diterpene synthase. Heterologous expression of the bifunctional terpene synthase TndC in Saccharomyces cerevisiae led to the discovery of a new diterpene backbone, talarodiene, harboring a benzo[a]cyclopenta[d]cyclooctane tricyclic fused ring system. The cyclization mechanism that converts geranylgeranyl diphosphate to the tricyclic hydrocarbon skeleton was investigated using 13C-labeling studies and stable isotope tracer experiments showed the biotransformation of talarodiene into talaronoid C.
Within- and between-subject reproducibility and variability in multi-modal, longitudinal brain networks
Authors: Nakuci Johan , Wasylyshyn Nick , Cieslak Matthew , Elliot James C. , Bansal Kanika , Giesbrecht Barry , Grafton Scott T. , Vettel Jean M. , Garcia Javier O. , Muldoon Sarah F. 
Published: May 2022

AbstractNetwork analysis provides new and important insights into the function of complex systems such as the brain by examining structural and functional networks constructed from diffusion Magnetic Resonance Imaging (dMRI), functional MRI (fMRI) and Electro/Magnetoencephalography (E/MEG) data. Although network models can shed light on cognition and pathology, questions remain regarding the importance of these findings, due in part to the reproducibility of the core measurements and subsequent modeling strategies. In order to ensure that results are reproducible, we need a better understanding of within- and between-subject variability over long periods of time. Here, we analyze a longitudinal, 8 session, multi-modal (dMRI, and simultaneous EEG-fMRI), and multiple task imaging data set. We first investigate the reproducibility of individual brain connections and network measures and find that across all modalities, within-subject reproducibility is higher than between-subject reproducibility, reaffirming the ability to detect individual differences in network structure in both structural and functional human brain networks. We see high variability in the reproducibility of pairwise connections between brain regions, but observe that in EEG-derived networks, during both rest and task, alpha-band connectivity is consistently more reproducible than networks derived from other frequency bands. Further, reproducible connections correspond to strong connections. Structural networks show a higher reliability in network statistics than functional networks, and certain measures such as synchronizability and eigenvector centrality are consistently less reliable than other network measures across all modalities. Finally, we find that structural dMRI networks outperform functional networks in their ability to identify individuals using a fingerprinting analysis. Our results highlight that functional networks likely reflect state-dependent variability not present in structural networks, and that the analysis of either structural or functional networks to study individual differences should depend on whether or not one wants to take into account state dependencies of the observed networks.
An actomyosin-polarized membrane reservoir mediates the unequal divisions ofDrosophilaneural stem cells
Authors: LaFoya Bryce , Prehoda Kenneth E. 
Published: May 2022

SummaryThe asymmetric divisions ofDrosophilaneural stem cells (NSCs) produce unequally sized siblings, with most volume directed into the sibling that retains the NSC fate. Sibling size asymmetry results from preferential expansion of the NSC sibling surface during division. Here we show that a polarized membrane reservoir constructed by the NSC in early mitosis provides the source for expansion. The reservoir is formed from membrane domains that contain folds and microvilli that become polarized by apically-directed cortical flows of actomyosin early in mitosis. When furrow ingression begins and internal pressure increases, the stores of membrane within the apical reservoir are rapidly consumed. Expansion is significantly diminished in NSCs that lack a reservoir, and membrane expansion equalizes when the reservoir is not polarized. Our results suggest that the cortical flows that remodel the plasma membrane during asymmetric cell division function to satisfy the dynamic surface area requirements of unequally dividing cells.