bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital Health Technology and Telemedicine-Based Hospital and Home Programs in Pulmonary Medicine During the COVID-19 Pandemic
Authors: Ilowite Jonathan , Lisker Gita , Greenberg Harly 
Published: March 2021

Background:
The current coronavirus disease 2019 (COVID-19) pandemic has caused a significant strain on medical resources throughout the world. A major shift to telemedicine and mobile health technologies has now taken on an immediate urgency. Newly developed devices designed for home use have facilitated remote monitoring of various physiologic parameters relevant to pulmonary diseases. These devices have also enabled home-based pulmonary rehabilitation programs. In addition, telemedicine and home care services have been leveraged to rapidly develop acute care hospital-at-home programs for the treatment of mild-to-moderate COVID-19 illness.

Areas of Uncertainty:
The benefit of remote monitoring technologies on patient outcomes has not been established in robust trials. Furthermore, the use of these devices, which can increase the burden of care, has not been integrated into current clinical workflows and electronic medical records. Finally, reimbursement for these telemedicine and remote monitoring services is variable.

Data Sources:
Literature review.

Therapeutic Advances:
Advances in digital technology have improved remote monitoring of physiologic parameters relevant to pulmonary medicine. In addition, telemedicine services for the provision of pulmonary rehabilitation and novel hospital-at-home programs have been developed. These new home-based programs have been adapted for COVID-19 and may also be relevant for the management of acute and chronic pulmonary diseases after the pandemic.

Conclusion:
Digital remote monitoring of physiologic parameters relevant to pulmonary medicine and novel hospital-at-home programs are feasible and may improve care for patients with acute and chronic respiratory-related disorders.
Advances in Treatment of Sleep-Disordered Breathing
Authors: Lou Becky X , Greenberg Harly , Korotun Maksim 
Published: March 2021

Background:
Sleep-disordered breathing, composed of obstructive sleep apnea (OSA) and central sleep apnea (CSA), affects millions of people worldwide carrying with it significant morbidity and mortality. Diagnosis is made by polysomnography, and severity of sleep apnea is determined by the apnea–hypopnea index (AHI). Positive airway pressure (PAP) therapy has been the gold standard in treating both OSA and CSA. PAP therapy can greatly reduce AHI burden as well as morbidity and mortality and improve quality of life.

Areas of Uncertainty:
However, patients report difficulties adhering to PAP therapy because of discomfort with mask interface, sensation of excessive pressure, and claustrophobia. Although other options exist to treat sleep apnea, such as mandibular advancement oral appliance devices, positional therapy, and surgery, these additional therapeutic modalities as current options have limitations. Emerging technology is now available to overcome hindrances to standard therapy.

Data Sources:
A literature search was performed from the following databases: PubMed, Cochrane Library (Cochrane Database of Systematic Reviews), and Cochrane Central Register of Controlled Trials, and FDA device database (clinicaltrial.gov).

Therapeutic Advances:
Other modalities of treating sleep-disordered breathing now include the hypoglossal nerve stimulator, which stimulates the hypoglossal nerve during sleep to alleviate airflow obstruction by contracting the genioglossus muscle thus treating OSA. Similarly, the phrenic nerve stimulator restores a more stable breathing pattern during sleep by stimulating the phrenic nerve to activate the diaphragm during CSA. Both nerve stimulators have been shown to reduce AHI severity and improve quality of life for patients suffering from sleep-disordered breathing.

Conclusions:
PAP therapy, although the gold standard, has limitations in the treatment of sleep apnea. New modalities such as hypoglossal nerve stimulator and phrenic nerve stimulator may help to overcome difficulties with adherence and offer new options for treatment of both obstructive and central sleep apnea.
Brain structure and function show distinct relations with genetic predispositions to mental health and cognition
Authors: Liu Shu , Smit Dirk J.A. , Abdellaoui Abdel , van Wingen Guido A. , Verweij Karin J.H. 
Published: March 2021

AbstractMental health and cognitive achievement are partly heritable. To identify the underlying neural mechanisms, we associated genetic predispositions to various mental health and cognitive traits with a large set of structural and functional brain measures from the UK Biobank (N=36,799). We show that genetic predispositions to attention deficit hyperactivity disorder, smoking initiation, and cognitive traits have stronger associations with brain structure than with brain function, whereas genetic predispositions to most other psychiatric disorders have stronger associations with brain function than with brain structure. These results reveal that genetic predispositions to mental health and cognitive traits have distinct brain profiles.
SARS-COV-2 antibody prevalence in patients on dialysis in the US in January 2021
Authors: Anand Shuchi , Montez-Rath Maria , Han Jialin , Cadden LinaCel , Hunsader Patti , Kerschmann Russell , Beyer Paul , Boyd Scott D , Garcia Pablo , Dittrich Mary , Block Geoffrey A , Parsonnet Julie , Chertow Glenn M 
Published: March 2021

ABSTRACTBackgroundTo estimate seroprevalence of SARS-CoV-2 antibodies in the US, the country with the world’s largest absolute numbers of COVID19 cases and deaths, we conducted a cross-sectional assessment from a sample of patients receiving dialysis in January 2021.MethodsWe tested remainder plasma of 21,424 patients receiving dialysis through the third-largest US dialysis organization, with facilities located nationwide. We used the Siemens spike protein receptor binding domain total antibody assay to estimate crude SARS-CoV-2 seroprevalence, and then estimated seroprevalence for the US dialysis and adult population by standardizing by age, sex and region. We also compared January 2021 seroprevalence and case-detection rates to that from a similar subsample of patients receiving dialysis who had been tested in July 2020.ResultsPatients in the sample were disproportionately from older age and minority race/ethnic groups. Seroprevalence of SARS-CoV-2 was 18.9% (95% CI: 18.3-19.5%) in the sample, 18.7% (18.1-19.2%) standardized to the US dialysis population, and 21.3% (20.3-22.3%) standardized to the US adult population (range 15.3-20.8% in the Northeast and South respectively). Younger age groups (18-44 years), and persons self-identifying as Hispanic or living in Hispanic neighborhoods, and persons living in the poorest neighborhoods were among the subgroups with the highest seroprevalence (25.9% (24.1-27.8%), 25.1% (23.6-26.4%), 24.8% (23.2-26.5%) respectively). Compared to data from July 2020, we observed diminished variability in seroprevalence by geographic region and urban-rural status. Estimated case detection rate increased from 14% to 23% in July 2020 to January 2021.ConclusionsA year after the first case of SARS-CoV-2 infection was detected in the US, fewer than one in four adults have evidence of SARS-CoV-2 antibodies. Vaccine roll out to majority minority neighborhoods and poorer neighborhoods will be critical to disrupting the spread of infection.FundingAscend Clinical Laboratories funded remainder-plasma testing.
AI-driven prediction of SARS-CoV-2 variant binding trends from atomistic simulations
Authors: Capponi Sara , Wang Shangying , Navarro Erik J. , Bianco Simone 
Published: March 2021

AbstractWe present a novel technique to predict binding affinity trends between two molecules from atomistic molecular dynamics simulations. The technique uses a neural network algorithm applied to a series of images encoding the distance between two molecules in time. We demonstrate that our algorithm is capable of separating with high accuracy non-hydrophobic mutations with low binding affinity from those with high binding affinity. Moreover, we show high accuracy in prediction using a small subset of the simulation, therefore requiring a much shorter simulation time. We apply our algorithm to the binding between several variants of the SARS-CoV-2 spike protein and the human receptor ACE2.
Make Interactive Complex Heatmaps in R
Authors: Gu Zuguang , Hübschmann Daniel 
Published: March 2021

AbstractHeatmap is a powerful visualization method on two-dimensional data to reveal patterns shared by subsets of rows and columns. InR, there are many packages that make heatmaps. Among them,ComplexHeatmapprovides rich tools for constructing highly customizable heatmaps. It can easily establish connections between information from multiple sources by automatically concatenating and adjusting multiple heatmaps as well as complex annotations, which makes it widely applied in data analysis in various fields, especially in Bioinformatics. Nevertheless, the limit ofComplexHeatmapstill exists. It only generates static plots which restricts deeper inspections on complex heatmaps,e.g., to look into a subset of rows and columns when a specific pattern of interest is observed from the heatmap. In this work, we described a newR/Bioconductor packageInteractiveComplexHeatmapthat brings interactivity toComplexHeatmap.InteractiveComplexHeatmapis designed with an easy-to-use interface where static complex heatmaps can be directly exported to an interactive Shiny web application only with one extra line of code. The interactive application contains comprehensive tools for manipulating heatmaps. Besides common tools as supported in other interactive heatmap packages,InteractiveComplexHeatmapadditionally supports,e.g., selecting over multiple heatmaps and searching heatmaps via row or column labels. Also,InteractiveComplexHeatmapprovides methods for exporting static heatmaps from other popular heatmap functions,e.g.,heatmap.2()orpheatmap(), to interactive heatmap applications. Finally,InteractiveComplexHeatmapprovides flexible functionalities for integrating interactive heatmap widgets into other Shiny applications.InteractiveComplexHeatmapprovides a user interface for self-defining response to the selection events on heatmaps, which helps to implement more complex Shiny web applications.
Genome-Wide Covariation in SARS-CoV-2
Authors: Cresswell-Clay Evan , Periwal Vipul 
Published: March 2021

AbstractThe SARS-CoV-2 virus causing the global pandemic is a coronavirus with a genome of about 30Kbase length [Song et al., 2019]. The design of vaccines and choice of therapies depends on the structure and mutational stability of encoded proteins in the open reading frames(ORFs) of this genome. In this study, we computed, using Expectation Reflection, the genome-wide covariation of the SARS-CoV-2 genome based on an alignment of ≈ 130000 SARS-CoV-2 complete genome sequences obtained from GISAID[Shu & McCauley, 2017]. We used this covariation to compute the Direct Information between pairs of positions across the whole genome, investigating potentially important relationships within the genome, both within each encoded protein and between encoded proteins. We then computed the covariation within each clade of the virus. The covariation detected recapitulates all clade determinants and each clade exhibits distinct covarying pairs.
Sexual conflict promotes species coexistence through negative frequency dependence
Authors: Gomez-Llano Miguel , Nilén Sofie , Moodie Iain , Svensson Erik I. 
Published: March 2021

AbstractA major challenge in community ecology is to understand the mechanisms promoting stable local coexistence. A necessary feature of local coexistence is that species show negative frequency dependence, rescuing rare species from exclusion. However, most studies have focused on ecological differences driving negative frequency dependence, ignoring non-ecological mechanisms such as reproductive interactions. Here, we combined field studies with behavioural and mesocosm experiments to investigate how reproductive interactions within and between species promote coexistence. Our results indicate that the intensity of male mating harassment and sexual conflict increases as species become more common, reducing female productivity and leading to negative frequency dependence. Moreover, field surveys reveal that negative frequency dependence operates in natural settings, consistent with our experimental results. These results suggest that sexual conflict can promote local coexistence and highlights the importance of studying reproductive interactions together with ecological differences to better understand the mechanisms promoting species coexistence.Significance statementResearch on the mechanisms promoting local species coexistence have focused on canonical ecological differences that increase intraspecific over interspecific competition. However, one intrinsic factor of species that can promote coexistence are the reproductive interactions. We performed a series of behavioural and mesocosm experiments manipulating species frequencies together with field observations and show that sexual conflict can decrease female fitness when species are common and promote local coexistence. Our results suggest that reproductive interactions are an understudied mechanism that can promote species coexistence even when species are ecologically equivalent.
Silkworm spinning: the programmed self-assembly from natural silk fibroin to superfibre
Authors: Song Kai , Wang Yejing , Dong Wenjie , Li Zhenzhen , He Huawei , Zhu Ping , Xia Qingyou 
Published: March 2021

AbstractSilkworm silk is one of the best natural protein fibers spun by the silkworm at ambient temperature and pressure using aqueous silk protein solution. It is a great challenge to reproduce high-performance artificial fibers comparable to natural silk by bionics for the incomplete understanding of silkworm spinning mechanism, especially the structure and assembly of natural silk fibroin (NSF) in the silk gland. Here, we studied the structure and assembly of NSF with the assistance of amphipol and digitonin. Our results showed NSFs were present as nanofibrils primarily composed of random coils in the silk gland. Metal ions were vital for the formation of NSF nanofibrils. The successive decrease in pH from posterior silk gland (PSG) to anterior silk gland (ASG) resulted in a gradual increase in NSF hydrophobicity. NSF nanofibrils were randomly arranged from PSG to ASG-1, and then self-assembled into herringbone-like patterns near the spinneret (ASG-2) ready for silkworm spinning. Our study reveals the mechanism by which silkworms cleverly utilize metal ions and pH gradient in the silk gland to drive the programmed self-assembly of NSF from disordered nanofibrils to anisotropic liquid crystalline spinning dope (herringbone-like patterns) for silkworm spinning, thus providing novel insights into silkworm/spider spinning mechanism and bionic creation of high-performance fibers.
G-quadruplex RNA motifs influence gene expression in the malaria parasitePlasmodium falciparum
Authors: Dumetz Franck , Chow Eugene Yui-Ching , Harris Lynne M. , Umar Mubarak I. , Jensen Anders , Chung Betty , Chan Ting Fung , Merrick Catherine J. , Kwok Chun Kit 
Published: March 2021

ABSTRACTG-quadruplexes are non-helical secondary structures that can foldin vivoin both DNA and RNA. In human cells, they can influence replication, transcription and telomere maintenance in DNA, or translation, transcript processing and stability of RNA. We have previously showed that G-quadruplexes are detectable in the DNA of the malaria parasitePlasmodium falciparum, despite a very highly A/T-biased genome with unusually few guanine-rich sequences. Here, we show that RNA G-quadruplexes can also form inP. falciparumRNA, using rG4-seq for transcriptome-wide structure-specific RNA probing. Many of the motifs, detected here via the rG4seeker pipeline, have non-canonical forms and would not be predicted by standardin silicoalgorithms. However,in vitrobiophysical assays verified the formation of non-canonical motifs. The G-quadruplexes in theP. falciparumtranscriptome are frequently clustered in certain genes and associated with regions encoding low-complexity peptide repeats. They are overrepresented in particular classes of genes, notably those that encodePfEMP1 virulence factors, stress response genes and DNA binding proteins.In vitrotranslation experiments andin vivomeasures of translation efficiency showed that G-quadruplexes can influence the translation ofP. falciparummRNAs. Thus, the G-quadruplex is a novel player in post-transcriptional regulation of gene expression in this major human pathogen.
Full-length native CGRP neuropeptide and its stable analogue SAX, but not CGRP peptide fragments, inhibit mucosal HIV-1 transmission
Authors: Bomsel Morgane , Sams Anette , Cohen Emmanuel , Sennepin Alexis , Siracusano Gabriel , Sanvito Francesca , Edvinsson Lars , Lopalco Lucia , Ganor Yonatan 
Published: March 2021

AbstractThe vasodilator neuropeptide calcitonin gene-related peptide (CGRP) plays both detrimental and protective roles in different pathologies. CGRP is also an essential component of the neuro-immune dialogue between nociceptors and mucosal immune cells. We previously reported that CGRP strongly inhibits human immunodeficiency virus type 1 (HIV-1) infection, by suprresing Langerhans cells (LCs)-mediated HIV-1 transfer to T-cells during trans-infection. To understand the requirements for CGRP receptor (CGRP-R) activation during inhibition of HIV-1 transmission, we here investigated the anti-HIV-1 activities of full-length native CGRP and its recently developed stable analogue SAX, as well as several CGRP peptide fragments containing its binding C-terminal and activating N-terminal regions. We show that SAX significantly inhibits LCs-mediated HIV-1 trans-infection but with lower potency than CGRP, while all CGRP peptide fragments tested have no effect. In addition, CGRP readily enters the epithelial compartment of mucosal tissues and does not modify the distribution and density of mucosal immune cells.In-vivo, a single CGRP treatment in humanized mice, before vaginal challenge with high-dose HIV-1, restricts the increase in plasma viral load and maintains higher CD4+ T-cell counts. Together, our results call for the optimization and design of CGRP analogues and agonists, which could be harnessed for prevention of mucosal HIV-1 transmission.
The force loading rate drives cell mechanosensing through both reinforcement and fluidization
Authors: Andreu Ion , Falcones Bryan , Hurst Sebastian , Chahare Nimesh , Quiroga Xarxa , Roux Anabel-Lise Le , Kechagia Zanetta , Beedle Amy E.M. , Elósegui-Artola Alberto , Trepat Xavier , Farré Ramon , Betz Timo , Almendros Isaac , Roca-Cusachs Pere 
Published: March 2021

AbstractCell response to force regulates essential processes in health and disease. However, the fundamental mechanical variables that cells sense and respond to remain unclear. Here we show that the rate of force application (loading rate) drives mechanosensing, as predicted by a molecular clutch model. By applying dynamic force regimes to cells through substrate stretching, optical tweezers, and atomic force microscopy, we find that increasing loading rates trigger talin-dependent mechanosensing, leading to adhesion growth and reinforcement, and YAP nuclear localization. However, above a given threshold the actin cytoskeleton undergoes fluidization and softens, decreasing loading rates and preventing reinforcement. By stretching rat lungsin vivo, we show that a similar phenomenon occurs at the organ level. Our results show that cell sensing of external forces and of passive mechanical parameters (like tissue stiffness) can be understood through the same mechanisms, driven by the properties under force of the mechanosensing molecules involved.
Mixed fatty acid-phospholipid protocell networks
Authors: Põldsalu Inga , Köksal Elif Senem , Gözen Irep 
Published: March 2021

AbstractSelf-assembled membranes composed of both fatty acids and phospholipids are both permeable for solutes and structurally stable, which was likely an advantageous combination for the development of primitive cells on the early Earth. Here we report on the solid surface-assisted formation of primitive mixed-surfactant membrane compartments,i.e.model protocells, from multilamellar lipid reservoirs composed of different ratios of fatty acids and phospholipids. Similar to the previously discovered enhancement of model protocell formation on solid substrates, we achieve spontaneous multi-step self-transformation of mixed surfactant reservoirs into closed surfactant containers, interconnected via nanotube networks. Some of the fatty acid containing compartments in the networks exhibit colony-like growth. We demonstrate that the compartments generated from fatty acid-containing phospholipid membranes feature increased permeability coefficients for molecules in the ambient solution, for fluorescein up to 7*10-6cm/s and for RNA up to 3.5*10-6cm/s. Our findings indicate that surface-assisted autonomous protocell formation and development, starting from mixed amphiphiles, is a plausible scenario for the early stages of the emergence of primitive cells.
Boundary convection during velocity sedimentation in the Optima analytical ultracentrifuge
Authors: Berkowitz Steven A. , Laue Thomas 
Published: March 2021

AbstractAnalytical ultracentrifugation (AUC) provides the most widely applicable, precise and accurate means for characterizing solution hydrodynamic and thermodynamic properties. In recent times AUC has found broad application in the biopharmaceutical industry as a first-principle means for quantitatively characterizing biopharmaceuticals. Boundary sedimentation velocity AUC (SV-AUC) analysis is widely used to assess protein aggregation, fragmentation and conformational variants in the same solvents used during drug development and production. SV-AUC is especially useful for the analysis of drug substance, drug product and dosing solution, where other techniques may exhibit solvent matrix issues or concentration limitations. Recently, the only manufacturer of the analytical ultracentrifuge, released its newest (third generation) analytical ultracentrifuge, the Optima, in early 2017 to replace its aging 2ndgeneration XL series ultracentrifuges. However, SV-AUC data from four Optima units used in conducting characterization work on adeno-associated virus (AAV) has shown evidence of sample convection. Further investigation reveals that this problem arises from the temperature control system design, which is prone to producing destabilizing temperature induced density gradients that can lead to density inversions. The observed convection impacts both the qualitative and quantitative data generated by the Optima. The problem is intermittent and variable in severity within a given Optima unit and between Optima units. This convection appears to be mainly associated with low rotor speeds and dilute samples in dilute solvents, such as AAV samples in formulation buffers containing relatively low concentrations of salts, sugars, etc. Under these conditions it is found that a sufficiently robust stabilizing density gradient is not always present during sedimentation, making the sample susceptible to convection by localized density inversions. Because SV-AUC is used as an analytical tool in making critical decisions in the development and quality control of biotherapeutics, it is imperative to alert users about this potential problem. In general special attention to data quality needs to be made by those researchers working with very large biopharmaceutical particles (e.g. gene therapy products that involve viral vectors or nanoparticles), where the conditions leading to convection are most likely to occur. It is important to note that the XL series analytical ultracentrifuges do not suffer from this problem, indicating that this problem is unique to the Optima. Attributes that reveal the presence of this problem and strategies for its elimination or minimization are provided.