bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of a Digital Health Intervention for Acute Myocardial Infarction Recovery
Authors: Bhardwaj Vinayak , Spaulding Erin M. , Marvel Francoise A. , LaFave Sarah , Yu Jeffrey , Mota Daniel , Lorigiano Ting-Jia , Huynh Pauline P. , Shan Rongzi , Yesantharao Pooja S. , Lee Matthias A. , Yang William E. , Demo Ryan , Ding Jie , Wang Jane , Xun Helen , Shah Lochan , Weng Daniel , Wongvibulsin Shannon , Carter Jocelyn , Sheidy Julie , McLin Renee , Flowers Jennifer , Majmudar Maulik , Elgin Eric , Vilarino Valerie , Lumelsky David , Leung Curtis , Allen Jerilyn K. , Martin Seth S. , Padula William V. 
Published: September 2021

Background:
Acute myocardial infarction (AMI) is a common cause of hospital admissions, readmissions, and mortality worldwide. Digital health interventions (DHIs) that promote self-management, adherence to guideline-directed therapy, and cardiovascular risk reduction may improve health outcomes in this population. The “Corrie” DHI consists of a smartphone application, smartwatch, and wireless blood pressure monitor to support medication tracking, education, vital signs monitoring, and care coordination. We aimed to assess the cost-effectiveness of this DHI plus standard of care in reducing 30-day readmissions among AMI patients in comparison to standard of care alone.

Methods:
A Markov model was used to explore cost-effectiveness from the hospital perspective. The time horizon of the analysis was 1 year, with 30-day cycles, using inflation-adjusted cost data with no discount rate. Currencies were quantified in US dollars, and effectiveness was measured in quality-adjusted life-years (QALYs). The results were interpreted as an incremental cost-effectiveness ratio at a threshold of $100,000 per QALY. Univariate sensitivity and multivariate probabilistic sensitivity analyses tested model uncertainty.

Results:
The DHI reduced costs and increased QALYs on average, dominating standard of care in 99.7% of simulations in the probabilistic analysis. Based on the assumption that the DHI costs $2750 per patient, use of the DHI leads to a cost-savings of $7274 per patient compared with standard of care alone.

Conclusions:
Our results demonstrate that this DHI is cost-saving through the reduction of risk for all-cause readmission following AMI. DHIs that promote improved adherence with guideline-based health care can reduce hospital readmissions and associated costs.
Management of acute kidney injury associated with Covid-19: what have we learned?
Authors: Cottam Daniel , Nadim Mitra K. , Forni Lui G. 
Published: September 2021

Purpose of review
Although initially kidney involvement in COVID-19 infection was felt to occur relatively infrequently, this has proved not to be the case. In critically ill patients with COVID-19, multiorgan failure including acute kidney injury (AKI) is common and is associated with an increased risk of mortality and morbidity. This review focuses briefly on the epidemiology and pathophysiology of COVID-19 associated AKI as well as options for management.

Recent findings
The risk factors for AKI are common to both noncovid-related AKI and COVID-19 associated AKI. Kidney injury in COVID-19 associated AKI may arise through several mechanisms, including not only direct effects on the kidney leading to tubular injury but also through the effects of treatment of multiorgan failure complicating infection. During surge conditions, the use of kidney replacement therapy has embraced all modalities including the use of peritoneal dialysis. The use of blood purification techniques has been proposed, but to date, the results are variable.

Summary
COVID-19 associated AKI is common, affecting approximately a quarter of patients hospitalized with COVID-19. Glomerular injury can occur, but in the main tubular injury seems most likely leading to AKI, which should be managed following clinical pathways informed by accepted guidelines.
Functional laryngectomy for the dysfunctional larynx: indications and outcomes in setting of prior chemoradiotherapy
Authors: Olinde Lindsay , Evangelista Lisa , Bewley Arnaud F. 
Published: September 2021

Purpose of review
To review the recent literature on indications for and functional outcomes following laryngectomy for severe laryngeal dysfunction.

Recent findings
The use of functional laryngectomy as a definitive treatment for severe laryngeal dysfunction is increasing as more patients with head and neck cancer are treated with definitive chemoradiotherapy. Data are emerging on the efficacy of this technique as measured by aspiration, recurrent pneumonias, enteral tube feeding dependence, and surgical complication rates. Though most patients have marked improvement in aspiration and oral intake, difficulties in swallowing and voicing functions may persist.

Summary
Functional laryngectomy is an effective treatment for end-stage laryngeal dysfunction. There is a clear benefit with regard to prevention of aspiration and alleviation of nothing by mouth status. However, qualitative speech and swallowing outcomes are less well studied, though available data suggest that many patients still suffer some degree of continued chronic impairment. More research is needed on these outcomes in order to appropriately counsel patients regarding long-term functional outcomes.
Culture of Interdisciplinary Collaboration in Nursing Research Training
Authors: Levites Strekalova Yulia A. 
Published: September 2021

Background
Establishing and maintaining collaborative scientific environments that can cultivate and benefit from a full range of talents is essential for the quality and influence of science. Inclusion of research training and career development interventions to expose nursing PhD students, postdocs, and junior faculty to team science stands to prepare graduates to effectively engage with interdisciplinary colleagues to conduct cutting-edge nursing research and compete successfully for precious research resources. To be effective, nursing research workforce development programs need to recognize and share a culture of interdisciplinarity.

Objectives
This project aims to develop, validate, and disseminate a theoretically grounded and methodologically rigorous tool for a cultural consensus analysis (CCA) of the culture of interdisciplinary collaboration in nursing research.

Methods
Culture can be defined as shared cognitive structures and consensus around culturally correct values, attitudes, and normative behaviors. This mixed-methods study employs CCA to assess construct validity and empirically determine a set of underlying socially learned and shared notions about the cultural domain of interdisciplinary collaboration in nursing research. The study will include three phases: (a) qualitative data collection and analysis to define the cultural domain of interdisciplinary collaborations in nursing research; (b) validation of the CCA tool with the use of cultural knowledge statements; and (c) application of the CCA tool to assess cultural differences among nursing trainees, junior faculty, and training directors. The study participant pool consists of National Institutes of Health–National Institute of Nursing Research awardees, including training directors of institutional training grants, pre- and postdoctoral trainees with individual fellowship training grants, and junior faculty with career development awards. Qualitative data will be analyzed to formulate cultural statements about the values and behaviors that promote interdisciplinary collaboration in nursing research. Subsequent survey data will be assessed using matrix algebra, principal component analysis, and the Stuart–Maxwell Marginal Homogeneity Test.

Discussion
The development and validation of a CCA tool is a novel approach to assess, support, and systematically examine interdisciplinary collaboration and team science in nursing research and training. However, the investigation of culture needs to remain value neutral, refrain from being prescriptive, and be sensitive to the emergence and dominance of one “right” culture.
Psychological and social risk factors associated with development of psychopathology, controlling for biological influence
Authors: Isaksson Johan , Zetterqvist Vendela , Ramklint Mia 
Published: September 2021

Purpose of review
To evaluate and summarize recent research investigating psychological, social and environmental risk factors for development of psychopathology in childhood, while controlling for biological (genetic) influences by using a matched sibling, twin or adoptee design.

Recent findings
Nineteen studies were included, of which eleven were longitudinal and eight were cohort studies. Included studies used adequate designs and statistical methods, controlled for unmeasured confounders and, in many cases, for other measured risk factors. None of the studies used the framework for environmental factors presented in the International Classification of Functioning, Disability and Health (ICF). The outcome variable psychopathology was rarely assessed using a diagnostic standard. The findings were sorted in five themes based on included exposures: ‘Social support, social rejection and perceived identity,’ ‘Early symptoms of psychopathology,’ ‘Antibiotic exposure,’ ‘Factors in the family’ and ‘Nature versus nurture’.

Summary
Using twin/sibling/adoptee designs, a number of unique predictors of psychopathology were found, even when controlling for familial confounders and other specified risk factors. Future studies of psychopathology development should benefit from longitudinal, genetically sensitive designs and from use of diagnostic standards for psychopathology outcome, and should also incorporate ICF for classification of risk factors.
Dysregulated immune responses in COVID-19 patients correlating with disease severity and invasive oxygen requirements
Authors: García-González Paulina , Tempio Fabián , Fuentes Camila , Merino Consuelo , Vargas Leonardo , Simon Valeska , Ramirez-Pereira Mirliana , Rojas Verónica , Tobar Eduardo , Landskron Glauben , Araya Juan Pablo , Navarrete Mariela , Bastias Carla , Tordecilla Rocío , Varas Macarena A. , Maturana Pablo , Marcoleta Andrés E. , Allende Miguel L. , Naves Rodrigo , Hermoso Marcela A. , Salazar-Onfray Flavio , Lopez Mercedes , Bono María Rosa , Osorio Fabiola 
Published: September 2021

AbstractThe prognosis of severe COVID-19 patients has motivated research communities to uncover mechanisms of SARS-CoV-2 pathogenesis also on a regional level. In this work, we aimed to understand the immunological dynamics of severe COVID-19 patients with different degrees of illness, and upon long-term recovery.We analyzed immune cellular subsets and SARS-CoV-2-specific antibody isotypes of 66 COVID-19 patients admitted to the Hospital Clínico Universidad de Chile, which were categorized according to the WHO ten-point clinical progression score. These included 29 moderate patients (score 4-5) and 37 severe patients under either high flow oxygen nasal cannula (18 patients, score 6), or invasive mechanical ventilation (19 patients, score 7-9), plus 28 convalescent patients and 28 healthy controls. Furthermore, six severe patients that recovered from the disease were longitudinally followed over 300 days.Our data indicate that severe COVID-19 patients display increased frequencies of plasmablasts, activated T cells and SARS-CoV-2-specific antibodies compared to moderate and convalescent patients. Remarkably, within the severe COVID-19 group, patients rapidly progressing into invasive mechanical ventilation show higher frequencies of plasmablasts, monocytes, eosinophils, Th1 cells and SARS-CoV-2-specific IgG than patients under high flow oxygen nasal cannula. These findings demonstrate that severe COVID-19 patients progressing into invasive mechanical ventilation show a distinctive type of immunity. In addition, patients that recover from severe COVID-19 begin to regain normal proportions of immune cells 100 days after hospital discharge and maintain high levels of SARS-CoV-2-specific IgG throughout the study, which is an indicative sign of immunological memory. Thus, this work can provide a useful benchmark for improvement of disease outcomes.
Yeast cells actively tune their membranes to phase separate at temperatures that scale with growth temperatures
Authors: Leveille Chantelle L. , Cornell Caitlin E. , Merz Alexey J. , Keller Sarah L. 
Published: September 2021

ABSTRACTMembranes of vacuoles, the lysosomal organelles in yeast, undergo extraordinary changes during the cell’s normal growth cycle. The cycle begins with a stage of rapid cell growth. Then, as glucose becomes scarce, growth slows, and the vacuole membranes phase-separate into micron-scale liquid domains. Recent studies suggest that these domains are important for yeast survival by laterally organizing membrane proteins that play a key role in a central signaling pathway conserved among eukaryotes (TORC1). An outstanding question in the field has been whether yeast stringently regulate the phase transition and how they respond to new physical conditions. Here, we measure transition temperatures – an increase of roughly 15°C returns vacuole membranes to a state that appears uniform across a range of growth temperatures. We find that broad populations of yeast grown at a single temperature regulate the transition to occur over a surprisingly narrow temperature range. Moreover, the transition temperature scales linearly with the growth temperature, demonstrating that the cells physiologically adapt to maintain proximity to the transition. Next, we ask how yeast adjust their membranes to achieve phase separation. Specifically, we test how levels of ergosterol, the main sterol in yeast, induce or eliminate membrane domains. We isolate vacuoles from yeast during their rapid stage of growth, when their membranes do not natively exhibit domains. We find that membrane domains materialize when ergosterol is depleted, contradicting the assumption that increases in ergosterol cause membrane phase separation in vivo, and in agreement with prior studies that use artificial and cell-derived membranes.SIGNIFICANCE STATEMENTPhase separation in membranes creates domains enriched in specific components. To date, the best example of micron-scale phase separation in the membrane of an unperturbed, living cell occurs in a yeast organelle called the vacuole. Recent studies indicate that the phases are functionally important, enabling yeast survival during periods of cellular stress. We have discovered that yeast regulate this phase transition; the temperature at which membrane components mix into a single phase is ~15°C above the growth temperature. To maintain this offset, yeast may tune the level of ergosterol (a molecule that is structurally similar to cholesterol) in their membranes. We find that reducing sterol levels in vacuole membranes causes them to phase separate, in contrast to previous assumptions.
SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells
Authors: Wang Ying , Yen Frederick S. , Zhu Xiphias Ge , Timson Rebecca C. , Weber Ross , Xing Changrui , Liu Yuyang , Allwein Benjamin , Luo Hanzhi , Yeh Hsi-Wen , Heissel Søren , Unlu Gokhan , Gamazon Eric R. , Kharas Michael G. , Hite Richard , Birsoy Kivanç 
Published: September 2021

SUMMARYGlutathione (GSH) is a small molecule thiol abundantly present in all eukaryotes with key roles in oxidative metabolism1. Mitochondria, as the major site of oxidative reactions, must maintain sufficient levels of GSH to perform protective and biosynthetic functions2. GSH is exclusively synthesized in the cytosol, yet the molecular machinery involved in mitochondrial GSH import remain elusive. Here, using organellar proteomics and metabolomics approaches, we identify SLC25A39, a mitochondrial membrane carrier of unknown function, to regulate GSH transport into mitochondria. SLC25A39 loss reduces mitochondrial GSH import and abundance without impacting whole cell GSH levels. Cells lacking both SLC25A39 and its paralog SLC25A40 exhibit defects in the activity and stability of ironsulfur cluster containing proteins. Moreover, mitochondrial GSH import is necessary for cell proliferationin vitroand red blood cell development in mice. Remarkably, the heterologous expression of an engineered bifunctional bacterial GSH biosynthetic enzyme (GshF) in mitochondria enabled mitochondrial GSH production and ameliorated the metabolic and proliferative defects caused by its depletion. Finally, GSH availability negatively regulates SLC25A39 protein abundance, coupling redox homeostasis to mitochondrial GSH import in mammalian cells. Our work identifies SLC25A39 as an essential and regulated component of the mitochondrial GSH import machinery.
Large-scale mRNA translation and the intricate effects of competition for the finite pool of ribosomes
Authors: Jain Aditi , Margaliot Michael , Gupta Arvind Kumar 
Published: September 2021

AbstractWe present a new theoretical framework for large-scale mRNA translation using a network of models called the ribosome flow model with Langmuir kinetics (RFMLK), interconnected via a pool of free ribosomes. The input to each RFMLK depends on the pool density, and it affects the initiation rate and the internal ribosome entry rates at each site along each RFMLK. Ribosomes that detach from an RFMLK due to termination or premature drop-off are fed back into the pool. We prove that the network always converges to a steady-state, and study its sensitivity to variations in the parameters. For example, we show that if the drop-off rate at some site in some RFMLK is increased then the pool density increases and consequently the steady-state production rate in all the other RFMLKs increases. Surprisingly, we also show that modifying a parameter of a certain RFMLK can lead to arbitrary effects on the densities along the modified RFMLK, depending on the parameters in the entire network. We conclude that the competition for shared resources generates an indirect and intricate web of mutual effects between the mRNA molecules, that must be accounted for in any analysis of translation.
RNANetMotif: identifying sequence-structure RNA network motifs in RNA-protein binding sites
Authors: Ma Hongli , Wen Han , Xue Zhiyuan , Li Guojun , Zhang Zhaolei 
Published: September 2021

AbstractRNA molecules can adopt stable secondary and tertiary structures, which is essential in mediating physical interactions with other partners such as RNA binding proteins (RBPs) and in carrying out their cellular functions. In vivo and in vitro experiments such as RNAcompete and eCLIP have revealed in vitro binding preferences of RBPs to RNA oligomers and in vivo binding sites in cells. Analysis of these binding data showed that the structure properties of the RNAs in these binding sites are important determinants of the binding events; however, it has been a challenge to incorporate the structure information into an interpretable model. Here we describe a new approach, RNANetMotif, which takes predicted secondary structure of thousands of RNA sequences bound by an RBP as input and uses a graph theory approach to recognize enriched subgraphs. These enriched subgraphs are in essence shared sequence-structure elements that are important in RBP-RNA binding. To validate our approach, we performed RNA structure modeling via discrete molecular dynamics folding simulations for selected 4 RBPs, and RNA-protein docking for LIN28. The simulation results, e.g., solvent accessibility and energetics, further support the biological relevance of the discovered network subgraphs.Author SummaryRNA binding proteins (RBPs) regulate every aspect of RNA biology, including splicing, translation, transportation, and degradation. High-throughput technologies such as eCLIP have identified thousands of binding sites for a given RBP throughout the genome. It has been shown by earlier studies that, in addition to nucleotide sequences, the structure and conformation of RNAs also play important role in RBP-RNA interactions. Analogous to protein-protein interactions or protein-DNA interactions, it is likely that there exist intrinsic sequence-structure motifs common to these RNAs that underlie their binding specificity to specific RBPs. It is known that RNAs form energetically favorable secondary structures, which can be represented as a graph, with nucleotides being nodes and backbone covalent bonds and base-pairing hydrogen bonds representing edges. We hypothesize that these graphs can be mined by graph theory approaches to identify sequence-structure motifs as enriched sub-graphs. In this article, we described the details of this approach, termed RNANetMotif and associated new concepts, namely EKS (Extended K-mer Subgraphs) and GraphK graph search algorithm. To test the utility of our approach, we conducted 3D structure modeling of selected RNA sequences through molecular dynamics (MD) folding simulation and evaluated the significance of the discovered RNA motifs by comparing their spatial exposure with other regions on the RNA. We believe that this approach has the novelty of treating the RNA sequence as a graph and RBP binding sites as enriched subgraph, which has broader applications beyond RBP-RNA interactions.
Epigenetic Remodeling by Vitamin C Potentiates the Differentiation of Mouse and Human Plasma Cells
Authors: Chen Heng-Yi , Alamonte-Loya Ana , Lay Fang-Yun , Johnson Eric , Gonzalez-Avalos Edahi , Yin Jieyun , Ma Qin , Wozniak Daniel J. , Harrison Fiona E. , Lio Chan-Wang Jerry 
Published: September 2021

AbstractAscorbate (vitamin C) is an essential micronutrient in humans. The chronic severe deficiency of ascorbate, termed scurvy, has long been associated with increased susceptibility to infections. How ascorbate affects the immune system at the cellular and molecular levels remained unclear. Here, from a micronutrient screen, we identified ascorbate as a potent enhancer for antibody response by facilitating the IL-21/STAT3-dependent plasma cell differentiation in mouse and human B cells. The effect of ascorbate is unique, as other antioxidants failed to promote plasma cell differentiation. Ascorbate is critical during early B cell activation by poising the cells to plasma cell lineage without affecting the proximal IL-21/STAT3 signaling and the overall transcriptome. Consistent with its role as a cofactor for epigenetic enzymes, ascorbate potentiates plasma cell differentiation by remodeling the epigenome via TET (Ten Eleven Translocation), the enzymes responsible for DNA demethylation by oxidizing 5-methylcytosines into 5-hydroxymethylcytosine (5hmC). Genome-wide 5hmC profiling identified ascorbate responsive elements (EAR) at the Prdm1 locus, including a distal element with a STAT3 motif overlapped with a CpG that was methylated and modified by TET in the presence of ascorbate. The results suggest that an adequate level of VC is required for antibody response and highlight how micronutrients regulate the activity of epigenetic enzymes to regulate gene expression. Our findings imply that epigenetic enzymes can function as sensors to gauge the availability of metabolites and influence cell fate decisions.