bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intervention for Alleviating Clinical Inertia in the Management of Urinary Incontinence
Authors: Artero-López Consuelo , Márquez-Hernández Verónica V. , Estevez-Morales María Teresa , Gutiérrez-Puertas Lorena , Aguilera-Manrique Gabriel , Granados-Gámez Genoveva 
Published: June 2021

PURPOSE:
The purpose of this study was to determine whether clinical inertia exists in the care of patients with urinary incontinence and to test the effects of an educational intervention designed to alleviate inertia related to care of urinary incontinence.

DESIGN:
Single-group, pretest/posttest design.

SUBJECTS AND SETTING:
The sample comprised 132 participants practicing in 6 medical-surgical inpatient care units at an urban hospital in Almería, Spain; 66 (50%) were RNs, and all other participants were unlicensed assistive personnel. Most participants (87.9%) were female; their average age was 43.99 years (SD = 7.85 years).

METHODS:
An educational intervention (online course) was provided. The main objective of the course was application of evidence-based knowledge for prevention and management of urinary incontinence in hospitalized patients. The course program comprised 3 didactic units: (1) introduction and evaluation of the patient with urinary incontinence, (2) care plans, and (3) instructions and rational use of absorbent products. Data collection included demographic and professional characteristics of respondents, desired results when caring for patients with incontinence, a medical record checklist, an occupational environment and satisfaction scale, and an assessment record of knowledge/skills and training activity satisfaction.

RESULTS:
After comparing the pre- and posttest scores of knowledge on urinary incontinence, significant differences were found before and after the intervention (z = −14.113, P = .000). Specifically, analysis revealed differences in caring actions related to urinary incontinence (z = −14.248, P = .000) and differences in direct observation of urinary incontinence practice following the intervention (z = −14.326, P = .000).

CONCLUSIONS:
Our findings indicate existence of inertia in nursing care for hospitalized patients with urinary incontinence. The educational intervention improved knowledge, observable nursing care activities related to incontinence management, and improved documentation of care.
A thematic analysis of Prison and Probation Ombudsman fatal incident reports involving prisoners on palliative/end-of-life care pathways in the long-term high security estate in England and Wales
Authors: Kirkham Joanne 
Published: June 2021

AbstractObjectivesIn this study, the clinical and non-clinical factors that may influence the provision of palliative/end of life care in long-term high security prisons in England and Wales are identified through the lens of Prison and Probation Ombudsman (PPO) fatal incident reports.MethodsThis work extends that of McParland and Johnston (2019) and contemporary literature published in the subsequent period to 2020 through a thematic analysis of fatal incident reports published by the PPO in the period 2014-2020. The results are discussed in context of the ‘Dying Well in Custody Charter’ and positioned within the extant literature.ConclusionsThe results suggest that prisoners in long-term high security prisons who are receiving palliative care are more likely than not to receive care that is comparable to that in the community. Directions for further research are also identified.
Loss-of-function of MFGE8 and protection against coronary atherosclerosis
Authors: Ruotsalainen Sanni E. , Surakka Ida , Mars Nina , Karjalainen Juha , Kurki Mitja , Kanai Masahiro , Krebs Kristi , Mishra Pashupati P. , Mishra Binisha H. , Sinisalo Juha , Palta Priit , Lehtimäki Terho , Raitakari Olli ,   Estonian Biobank research team, Milani Lili ,   The Biobank Japan Project, Okada Yukinori ,   FinnGen, Palotie Aarno , Widen Elisabeth , Daly Mark J. , Ripatti Samuli 
Published: June 2021

AbstractCardiovascular diseases are the leading cause of premature death and disability worldwide, with both genetic and environmental determinants. While genome-wide association studies have identified multiple genetic loci associated with cardiovascular diseases, exact genes driving these associations remain mostly uncovered. Due to Finland’s population history, many deleterious and high-impact variants are enriched in the Finnish population giving a possibility to find genetic associations for protein-truncating variants that likely tie the association to a gene and that would not be detected elsewhere.In FinnGen, a large Finnish biobank study, we identified an inframe insertion rs534125149 in MFGE8 to have protective effect against coronary atherosclerosis (OR = 0.75, p = 2.63×10-16) and related endpoints. This variant is highly enriched in Finland (70-fold compared to Non-Finnish Europeans) with allele frequency of 3% in Finland. The protective association was replicated in meta-analysis of biobanks of Japan and Estonian (OR = 0.75, p = 5.41×10-7).Additionally, we identified a splice acceptor variant rs201988637 in MFGE8, independent of the rs534125149 and similarly protective in relation to coronary atherosclerosis (OR = 0.72, p = 7.94×10-06) and related endpoints, with no significant risk-increasing associations. The protein-truncating variant was also associated with lower pulse pressure, pointing towards a function of MFGE8 in arterial stiffness and aging also in humans in addition to previous evidence in mice. In conclusion, our results show that inhibiting the production of lactadherin could lower the risk for coronary heart disease substantially.
Development of a digitally-obtainable 10-year all-cause mortality risk score based on data from 497,712 UK Biobank participants
Authors: Colombo Michele , Dolezalova Nikola , Despotovic Aleksa , Reed Angus B. , Morelli Davide , Aral Mert , Plans David 
Published: June 2021

AbstractBackgroundAll-cause mortality (ACM) scores are a useful tool for identifying individuals with decreased life expectancy. An interpretable score consisting of smartphone-obtainable variables could allow for long-term management of individual health and support the next generation of healthcare monitoring and preventative practices. The aim of this study was to develop a 10-year ACM risk score using the UK Biobank dataset, using only digitally-obtainable variables.MethodsThe models were developed using the full UK Biobank cohort comprising nearly 500,000 individuals. We extracted 399 features from the dataset and, through a data-driven feature selection process with subsequent clinical review, identified 34 features for the final model. As part of the study, we compared two survival analysis approaches: Cox proportional hazards model and DeepSurv, a deep learning-based survival analysis algorithm.ResultsBefore feature selection, Cox performed similarly to DeepSurv, achieving a c-index of 0.771 (95% CI 0.770–0.772) and 0.774 (95% CI 0.772–0.775) on the test dataset, respectively. Using the selected 34 features, the c-index of Cox decreased slightly to 0.770 (95% CI 0.769–0.770) and DeepSurv to 0.758 (95% CI 0.755–0.762). The models show excellent calibration at 10 years.ConclusionsThis study improves on a previous smartphone-compatible score, C-Score, by incorporating non-modifiable factors in addition to variables which can be actively modified to reduce risk. This score is comprehensive, easily interpretable and actionable, and as such, could provide a powerful tool for preventative healthcare.
Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of the matricellular protein Mindin
Authors: Badarinath Krithika , Dam Binita , Kataria Sunny , Zirmire Ravindra K. , Dey Rakesh , Singh Randhir , Masudi Tafheem A. , Sambath Janani , Kumar Prashanth , Gulyani Akash , He You-Wen , Krishna Sudhir , Jamora Colin 
Published: June 2021

SummaryIntratumoral heterogeneity poses a major challenge in designing effective anti-cancer strategies. Accumulating evidence suggests that this heterogeneity arises from cancer stem cells (CSCs) that also drives tumor aggressiveness and drug resistance. The stemness of CSCs are preserved by an ill-defined combination of intrinsic and external factors and is particularly intriguing since they exist within a sea of similar cells at various degrees of differentiation. In models of cutaneous squamous cell carcinoma (cSCC), we discovered a non-EMT function for the transcription factor Snail in maintaining stemness of keratinocytes. This is accomplished by the secretion of the matricellular protein Mindin from Snail expressing cells, which creates a protective niche that impedes differentiation. In an autocrine fashion, extracellular Mindin activates a Src –STAT3 pathway to reinforce the stem/progenitor phenotype and disruption of this signalling module in human cSCC attenuates tumorigenesis. The expression of Mindin in multiple carcinomas, and its critical role in cancer progression suggests that it would be a promising target for therapeutic intervention.
A comprehensive approach to artifact-free sample preparation and the assessment of mitochondrial morphology in tissue and cultured cells
Authors: Hinton Antentor , Katti Prasanna , Christensen Trace A. , Mungai Margaret , Shao Jianqiang , Zhang Liang , Trushin Sergey , Alghanem Ahmad , Jaspersen Adam , Geroux Rachel E. , Neikirk Kit , Biete Michelle , Lopez Edgar Garza , Vue Zer , Beasley Heather K. , Marshall Andrea G. , Ponce Jessica , Bleck Christopher K. E. , Hicsasmaz Innes , Murray Sandra A. , Edmonds Ranthony A.C. , Dajles Andres , Koo Young Do , Bacevac Serif , Salisbury Jeffrey L. , Pereira Renata O. , Glancy Brian , Trushina Eugenia , Abel E. Dale 
Published: June 2021

SummaryMitochondrial dynamics (fission, fusion, and the formation of nanotunnels) and morphology are very sensitive to the cellular environment. Mitochondria may be adversely affected by oxidative stress, changes in calcium levels, and hypoxia. Investigating the precise relationship between organelle structure and function requires methods that can adequately preserve mitochondria while providing accurate, quantitative measurements of morphological attributes. Here, we demonstrate a practical approach for preserving and measuring fine structural changes using two-dimensional, high-resolution electron micrographs. This approach is further applicable for three-dimensional volume renderings, obtained using serial block-face and focused ion beam-scanning electron microscopy, highlighting the specific advantages of these techniques. Additionally, this study defines a set of quantifiable metrics that can be applied to measure mitochondrial architecture and other organellar structures. Finally, we validated specimen preparation methods that avoid the introduction of morphological artifacts that may interfere with mitochondrial appearance and do not require whole-animal perfusion.
Implicit agency is related to gamma power changes in an automatic imitation task
Authors: Ulloa José Luis , Vastano Roberta , Jensen Ole , Brass Marcel 
Published: June 2021

ABSTRACTOften we have a feeling that we can control effects in the external world through our actions. The role of action processing associated with this implicit form of agency is still not clear. In this study, we used automatic imitation and electroencephalography to investigate neural oscillations associated with action processing and its possible contribution to implicit agency. Brain activity was recorded while participants performed actions (congruent or incongruent with a displayed finger movement) which subsequently triggered an outcome (a tone). We used a time estimation task to measure intentional binding (an index of implicit agency). We observed a decrease of alpha, beta and gamma power for congruent compared to incongruent actions and increased theta power for incongruent compared to congruent actions. Crucially, participants who showed greater intentional binding for congruent versus incongruent actions also presented greater gamma power differences. Alpha, beta and theta power were modulated by congruency but were unrelated to intentional binding. Our study suggests that an increased implicit agency for facilitated actions is associated with changes in gamma power. Our study also contributes to a characterization of neural oscillations in automatic imitation.
Integrative analyses of convergent adaptation in sympatric extremophile fishes
Authors: Greenway Ryan , De-Kayne Rishi , Brown Anthony P. , Camarillo Henry , Delich Cassandra , McGowan Kerry L. , Nelson Joel , Arias-Rodriguez Lenin , Kelley Joanna L. , Tobler Michael 
Published: June 2021

SummaryThe evolution of independent lineages along replicated environmental gradients frequently results in convergent adaptation, yet the degree to which convergence is present across multiple levels of biological organization is often unclear. Additionally, inherent biases associated with shared ancestry and variation in selective regimes across geographic replicates often pose challenges for confidently identifying patterns of convergence. We investigated a system in which three species of poeciliid fishes sympatrically occur in a toxic spring rich in hydrogen sulfide (H2S) and an adjacent nonsulfidic stream to examine patterns of adaptive evolution across levels of biological organization. We found convergence in morphological and physiological traits and genome-wide patterns of gene expression among all three species. In addition, there were shared signatures of selection on genes encoding H2S toxicity targets in the mitochondrial genomes of each species. However, analyses of nuclear genomes revealed neither evidence for substantial genomic islands of divergence around genes involved in H2S toxicity and detoxification nor substantial congruence of strongly differentiated regions across population pairs. These non-convergent, heterogenous patterns of genomic divergence may indicate that sulfide tolerance is highly polygenic, with shared allele frequency shifts present at many loci with small effects along the genome. Alternatively, H2S tolerance may involve substantial genetic redundancy, with non-convergent lineage-specific variation at multiple loci along the genome underpinning similar changes in phenotypes and gene expression. Overall, we demonstrate variability in the extent of convergence across organizational levels and highlight the challenges of linking patterns of convergence across scales.
A novel live cell imaging assay reveals regulation of endosome maturation
Authors: Podinovskaia Maria , Prescianotto-Baschong Cristina , Buser Dominik P. , Spang Anne 
Published: June 2021

AbstractCell-cell communication is an essential process in life, with endosomes acting as key organelles for regulating uptake and secretion of signaling molecules. Endocytosed material is accepted by the sorting endosome where it either is sorted for recycling or remains in the endosome as it matures to be degraded in the lysosome. Investigation of the endosome maturation process has been hampered by the small size and rapid movement of endosomes in most cellular systems. Here, we report an easy versatile live-cell imaging assay to monitor endosome maturation kinetics, which can be applied to a variety of mammalian cell types. Acute ionophore treatment led to enlarged early endosomal compartments that matured into late endosomes and fused with lysosomes to form endolysosomes. Rab5-to-Rab7 conversion and PI(3)P formation and turn over were recapitulated with this assay and could be observed with a standard widefield microscope. We used this approach to show that Snx1- and Rab11-dependent endosomal recycling occurred throughout endosome maturation and was uncoupled from Rab conversion. In contrast, efficient endosomal acidification was dependent on Rab conversion. The assay provides a powerful tool to further unravel various aspects of endosome maturation.
A prosocial character of head-gaze aversion in common marmosets
Authors: Spadacenta S. , Dicke P.W. , Thier P. 
Published: June 2021

ABSTRACTGaze aversion is a behavior adopted by several mammalian and non-mammalian species in response to eye contact and usually interpreted as reaction to perceived threat. Unlike many other primates, common marmosets (Callithrix jacchus) are thought to have high tolerance for direct gaze, barely exhibiting gaze avoidance towards conspecifics and humans. Here we show that this does not hold for marmosets interacting with a familiar experimenter who suddenly establishes eye contact in a playful interaction (“peek-a-boo”). In video footage synchronously recorded from the two agents, we found that our monkeys consistently alternated between eye contact and head-gaze aversion. The striking similarity with the gaze aversion’s dynamics exhibited by human infants interacting with their caregivers suggests a shared behavioral strategy to disengage temporarily from overwhelming social stimulation, in order to prepare for a new round of rewarding, affiliative face-to-face interaction. The potential of our finding for a marmoset model of autism is discussed.
N4-hydroxycytidine and inhibitors of dihydroorotate dehydrogenase synergistically suppress SARS-CoV-2 replication
Authors: Stegmann Kim M. , Dickmanns Antje , Heinen Natalie , Groß Uwe , Görlich Dirk , Pfaender Stephanie , Dobbelstein Matthias 
Published: June 2021

ABSTRACTEffective therapeutics to inhibit the replication of SARS-CoV-2 in infected individuals are still under development. The nucleoside analogue N4-hydroxycytidine (NHC), also known as EIDD-1931, interferes with SARS-CoV-2 replication in cell culture. It is the active metabolite of the prodrug Molnupiravir (MK-4482), which is currently being evaluated for the treatment of COVID-19 in advanced clinical studies. Meanwhile, inhibitors of dihydroorotate dehydrogenase (DHODH), by reducing the cellular synthesis of pyrimidines, counteract virus replication and are also being clinically evaluated for COVID-19 therapy. Here we show that the combination of NHC and DHODH inhibitors such as teriflunomide, IMU-838/vidofludimus, and BAY2402234, strongly synergizes to inhibit SARS-CoV-2 replication. While single drug treatment only mildly impaired virus replication, combination treatments reduced virus yields by at least two orders of magnitude. We determined this by RT-PCR, TCID50, immunoblot and immunofluorescence assays in Vero E6 and Calu-3 cells infected with wildtype and the Alpha and Beta variants of SARS-CoV-2. We propose that the lack of available pyrimidine nucleotides upon DHODH inhibition increases the incorporation of NHC in nascent viral RNA, thus precluding the correct synthesis of the viral genome in subsequent rounds of replication, thereby inhibiting the production of replication competent virus particles. This concept was further supported by the rescue of replicating virus after addition of pyrimidine nucleosides to the media. Based on our results, we suggest combining these drug candidates, which are currently both tested in clinical studies, to counteract the replication of SARS-CoV-2, the progression of COVID-19, and the transmission of the disease within the population.SIGNIFICANCEThe strong synergy displayed by DHODH inhibitors and the active compound of Molnupiravir might enable lower concentrations of each drug to antagonize virus replication, with less toxicity.Both Molnupiravir and DHODH inhibitors are currently being tested in advanced clinical trials or are FDA-approved for different purposes, raising the perspective of rapidly testing their combinatory efficacy in clinical studies.Molnupiravir is currently a promising candidate for treating early stages of COVID-19, under phase II/III clinical evaluation. However, like Remdesivir, it appears only moderately useful in treating severe COVID-19. Since the combination inhibits virus replication far more strongly, and since DHODH inhibitors may also suppress excessive immune responses, the combined clinical application bears the potential of alleviating the disease burden even at later stages.
Disease modeling by efficient genome editing using a near PAM-less base editorin vivo
Authors: Rosello Marion , Serafini Malo , Mione Marina C , Concordet Jean-Paul , Del Bene Filippo 
Published: June 2021

AbstractBase Editors are emerging as an innovative technology to introduce point mutations in complex genomes. So far, the requirement of an NGG Protospacer Adjacent Motif (PAM) at a suitable position often limits the editing possibility to model human pathological mutations in animals. Here we show that, using the CBE4max-SpRY variant recognizing the NRN PAM sequence, we could introduce point mutations for the first time in an animal model and achieved up to 100% efficiency, thus drastically increasing the base editing possibilities. With this near PAM-less base editor we could simultaneously mutate several genes and developed a co-selection method to identify the most edited embryos based on a simple visual screening. Finally, we applied our method to create a new zebrafish model for melanoma predisposition based on the simultaneous editing of multiple genes. Altogether, our results considerably expand the Base Editor application to introduce human disease-causing mutations in zebrafish.
Enhanced fitness of SARS-CoV-2 variant of concern B.1.1.7, but not B.1.351, in animal models
Authors: Ulrich Lorenz , Halwe Nico Joel , Taddeo Adriano , Ebert Nadine , Schön Jacob , Devisme Christelle , Trüeb Bettina Salome , Hoffmann Bernd , Wider Manon , Bekliz Meriem , Essaidi-Laziosi Manel , Schmidt Marie Luisa , Niemeyer Daniela , Corman Victor Max , Kraft Anna , Godel Aurélie , Laloli Laura , Kelly Jenna N. , Breithaupt Angele , Wylezich Claudia , Veiga Inês Berenguer , Gultom Mitra , Adea Kenneth , Meyer Benjamin , Eberhardt Christiane , Thomann Lisa , Gsell-Albert Monika , Labroussaa Fabien , Jores Jörg , Summerfield Artur , Drosten Christian , Eckerle Isabella Anne , Dijkman Ronald , Hoffmann Donata , Thiel Volker , Beer Martin , Benarafa Charaf 
Published: June 2021

AbstractEmerging variants of concern (VOCs) drive the SARS-CoV-2 pandemic. We assessed VOC B.1.1.7, now prevalent in several countries, and VOC B.1.351, representing the greatest threat to populations with immunity to the early SARS-CoV-2 progenitors. B.1.1.7 showed a clear fitness advantage over the progenitor variant (wt-S614G) in ferrets and two mouse models, where the substitutions in the spike glycoprotein were major drivers for fitness advantage. In the “superspreader” hamster model, B.1.1.7 and wt-S614G had comparable fitness, whereas B.1.351 was outcompeted. The VOCs had similar replication kinetics as compared to wt-S614G in human airway epithelial cultures. Our study highlights the importance of using multiple models for complete fitness characterization of VOCs and demonstrates adaptation of B.1.1.7 towards increased upper respiratory tract replication and enhanced transmission in vivo.Summary sentenceB.1.1.7 VOC outcompetes progenitor SARS-CoV-2 in upper respiratory tract replication competition in vivo.