bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world evidence for factors associated with maintenance treatment practices among US adults with autoimmune hepatitis
Authors: Bittermann Therese , Yagan Lina , Kathawate Ranganath G. , Weinberg Ethan M. , Peyster Eliot G. , Lewis James D. , Levy Cynthia , Goldberg David S. 
Published: June 2024

Background and Aims:
While avoidance of long-term corticosteroids is a common objective in the management of autoimmune hepatitis (AIH), prolonged immunosuppression is usually required to prevent disease progression. This study investigates the patient and provider factors associated with treatment patterns in US patients with AIH.

Approach and Results:
A retrospective cohort of adults with the incident and prevalent AIH was identified from Optum’s deidentified Clinformatics Data Mart Database. All patients were followed for at least 2 years, with exposures assessed during the first year and treatment patterns during the second. Patient and provider factors associated with corticosteroid-sparing monotherapy and cumulative prednisone use were identified using multivariable logistic and linear regression, respectively.
The cohort was 81.2% female, 66.3% White, 11.3% Black, 11.2% Hispanic, and with a median age of 61 years. Among 2203 patients with ≥1 AIH prescription fill, 83.1% received a single regimen for >6 months of the observation year, which included 52.2% azathioprine monotherapy, 16.9% azathioprine/prednisone, and 13.3% prednisone monotherapy. Budesonide use was uncommon (2.1% combination and 1.9% monotherapy). Hispanic ethnicity (aOR: 0.56; p = 0.006), cirrhosis (aOR: 0.73; p = 0.019), osteoporosis (aOR: 0.54; p=0.001), and top quintile of provider AIH experience (aOR: 0.66; p = 0.005) were independently associated with lower use of corticosteroid-sparing monotherapy. Cumulative prednisone use was greater with diabetes (+441 mg/y; p = 0.004), osteoporosis (+749 mg/y; p < 0.001), and highly experienced providers (+556 mg/y; p < 0.001).

Conclusions:
Long-term prednisone therapy remains common and unexpectedly higher among patients with comorbidities potentially aggravated by corticosteroids. The greater use of corticosteroid-based therapy with highly experienced providers may reflect more treatment-refractory disease.
Maternal Syphilis Leading to High Efficiency In Utero Transmission of Antiretroviral Resistant HIV: Intersection of Two Pandemics
Authors: Homans James , Blieden Carla 
Published: June 2024

Background:
Testing for syphilis and HIV is indicated in prenatal care in the United States. Effective antiretroviral therapy during pregnancy reduces mother-to-child HIV transmission (MTCT) to less than 1%. Syphilis infection in pregnant women with unsuppressed HIV increases the risk of MTCT, usually in utero. The incidences of syphilis in women of childbearing age and corresponding congenital syphilis are increasing in the United States.

Methods:
We report 3 cases of in utero HIV transmission associated with maternal syphilis that occurred during the ongoing syphilis epidemic.

Results:
All 3 women had untreated HIV infection and active syphilis with placentitis during late pregnancy. Their newborns were found to have symptomatic congenital syphilis and HIV infection from in utero transmission. The babies’ antiretroviral resistance patterns were nearly identical to their mothers’.

Conclusions:
When untreated syphilis and uncontrolled HIV coincide in pregnancy, there is a high likelihood of in utero mother-to-child HIV transmission. The current syphilis epidemic in the United States may lead to an increase in MTCT.
Clinical Significance of Mucor in Airway Culture of Immunocompetent Patients With Chronic Lung Disease
Authors: Rizik Suha , Bentur Lea , Bar-Yoseph Ronen , Szwarcwort Moran , Pollak Dina , Gur Michal , Meir Michal 
Published: June 2024

Objectives:
Mucor within the airways of immunocompromised patients often signifies an invasive life-threatening infection. However, its significance in immunocompetent patients with chronic lung diseases is less clear. We aimed to assess the clinical implication of mucor in airway-secretion cultures of these patients.

Methods:
A single-center retrospective cohort study was performed. Patients with cystic fibrosis (CF), primary ciliary dyskinesia (PCD) or non-CF/non-PCD bronchiectasis followed in our Pediatric Pulmonary Institute, with sputum or bronchoalveolar lavage cultures growing Mucorales molds in the years 2010–2022, were included. Demographic and clinical parameters such as body mass index and spirometry values (forced expiratory volume at 1 second) were collected and compared with values up to 12 months prior to and following the index (positive culture) visit.

Results:
A total of 27 patients of whom 22 (82%) patients were with CF, 3 with PCD (11%) and 2 (7%) with non-CF/non-PCD bronchiectasis were included. Median age was 21.8 (14.9–32.1) years, with forced expiratory volume at 1 second of 62.8% ± 21.9% at the index visit. None of the patients developed disseminated disease, none had clinical or radiological evidence of fungal disease and none required antifungal therapy. Throughout the 12 months prior to and following the positive cultures, no significant changes were noted in body mass index, forced expiratory volume at 1 second, frequency of pulmonary exacerbations, days of hospitalization or days of antibiotic treatment.

Conclusions:
Evidence of mucor in airway cultures of immunocompetent patients with chronic lung disease does not necessarily signify clinical deterioration nor suggests invasive fungal disease. Larger, long-term prospective studies are required to obviate the need for a thorough evaluation in these patients.
Environmental Scan of Online Government Complementary Feeding Resources in the United States
Authors: Thompson Kelsey L. , Graf Michelle D. 
Published: June 2024

Abstract

Background:
Parents commonly seek online sources of information on the important complementary feeding period, but the accuracy of these sources varies. The 21st Century Integrated Digital Experience Act (IDEA) states federal government resources should be accurate and user-friendly; however, the quantity, quality, and accuracy of federal resources on complementary feeding is unknown.

Methods:
An environmental scan of online federal, parent-facing resources about complementary feeding was conducted. The authors reviewed federal resources for concordance of information with the Dietary Guidelines for Americans (DGA). Quality was evaluated using the Patient Education Materials Assessment Tool.

Results:
A total of 112 resources across 2 federal government departments. Overall quality was high as was concordance with recommendations from the DGA for age of complementary food introduction, foods to introduce, and foods to avoid. Allergenic food introduction and textured food progression recommendations were less consistent. Recommendations for improvements to federal resources are made.

Clinical Implications:
This environmental scan only included federal resources for CF. Parents may be accessing other, non-federal resources online. However, given the enactment of IDEA, it is expected that these federal resources will be up-to-date and user-friendly, which was not always the case. Nurses should review the DGA guidelines for complementary feeding and provide evidence-based anticipatory guidance to families, focusing especially on allergenic food introduction and textured food progression. Future complementary feeding interventions may benefit from directing families to online exemplars from federal sources.
Modelling the dynamics of product adoption and abandonment
Authors: Kong Lingju 
Published: June 2024

We introduce a new compartmental differential equation model to examine the dynamics of user adoption and abandonment within a product context. This model features a nonlinear adoption rate and encompasses two distinct abandonment dynamics: infectious abandonment stemming from interactions among current and past users, and non-infectious abandonment induced by mass media, advertisements or the emergence of new products. Our exploration encompasses discussions on the existence and stability of model equilibria, as well as the derivation of a critical threshold quantity that regulates the model dynamics. Additionally, we establish criteria for backward and forward bifurcations and various forms of Hopf bifurcation. Detailed scrutiny of an associated optimal control problem is undertaken, starting with the establishment of the existence of an optimal control pair, followed by the determination of the requisite system conditions for this control pair. Extensive numerical simulations are conducted to validate the theoretical findings. Finally, we showcase the model’s efficacy by fitting it to historical data on Facebook’s daily active users, employing the derived parameter values to predict future user counts.
Evaluation of a novel digital ostomy device on leakage incidents, quality of life, mental well-being, and patient self-care: an interventional, multicentre clinical trial
Authors: Brady Richard R.W. , Sheard Diane , Alty Mandie , Vestergaard Martin , Boisen Esben Bo , Ainsworth Rachel , Hansen Helle Doré , Ajslev Teresa Adeltoft 
Published: June 2024

AbstractBackgroundMost people with a stoma worry about leakage, and a quarter experience leakage of stomal effluent outside baseplate on a monthly basis. Leakage has additional physical and psychosocial consequences, for instance peristomal skin complications, feeling unable to cope and self-isolation.MethodAn interventional, single-arm, multi-centre, study was undertaken in United Kingdom, to evaluate a novel digital leakage notification system for ostomy care including a Support Service (=Test Product) for 12 weeks in patients with a recent stoma formation (≤9 months). Patients completed questionnaires at baseline and after 4, 6, 8, 10 and 12 weeks, evaluating leakage episodes, Ostomy Leak Impact (tool containing three domains) and patient self-management (by PAM-13). Additionally, mental well-being (by WHO-5) and quality of life (QoL) (by EQ-5D-5L) were assessed. Outcomes between baseline and final evaluation were compared by generalised linear- and linear mixed models.Results92 patients (ITT population) were recruited with a mean age of 49.4-years (range 18-81 years). 80% had an ileostomy and 53% were female. After 12 weeks use of the Test Product, a significant decrease in mean episodes of leakage outside the baseplate (1.57 versus 0.93,P<0.046) was observed. Ostomy Leak Impact scores improved across all three domains (P<0.001), indicating less embarrassment, increased engagement in social activities, and increased control. Patient self-management also improved significantly (PAM-13 score: Δ6.6,P<0.001), as did the WHO-5 well-being index (Δ8.0,P<0.001). Lastly, EQ-5D-5L-profile-scores tended to improve (P=0.075).ConclusionA new digital leakage notification system demonstrated strong improvements to patients’ stoma self-care, mental well-being, and QoL.What does this paper add to the literature?Sensor technology embedded in supporting ostomy solutions can notify users about leakage seeping underneath the baseplate and thus secure a timely change of the baseplate before effluent may reach outside the baseplate soiling clothes or bedsheets. The technology showed potential in increasing quality of life for people with a stoma.
Macroscopic label-free biomedical imaging with shortwave infrared Raman scattering
Authors: Arús Bernardo A. , Yiu Joycelyn , Lingg Jakob G. P. , Hofmann Anja , Fumo Amy R. , Ji Honglei , Jethwa Carolin , Park Roy K. , Henderson James , Mishra Kanuj , Mukha Iuliia , Stiel Andre C. , Santovito Donato , Weber Christian , Reeps Christian , Rohm Maria , Bartelt Alexander , Valdez Tulio A. , Chmyrov Andriy , Bruns Oliver T. 
Published: June 2024

SummaryShortwave infrared (SWIR) imaging provides enhanced tissue penetration and reduced autofluorescence in clinical and pre-clinical applications. However, existing applications often lack the ability to probe chemical composition and molecular specificity without the need for contrast agents. Here, we present a SWIR imaging approach that visualizes spontaneous Raman scattering with remarkable chemical contrast deep within tissue across large fields of view. Our results demonstrate that Raman scattering overcomes autofluorescence as the predominant source of endogenous tissue background at illumination wavelengths as short as 892 nm. We highlight the versatility of SWIR Raman imaging throughin vivomonitoring of whole-body tissue composition dynamics and non-invasive detection of fatty liver disease in mice, and identification of calcification and lipids in unfixed human atherosclerotic plaques. Moreover, our approach facilitates the visualization of nerves embedded in fatty tissue, a major advancement for surgical applications. With a simple wide-field setup orthogonal to fluorescence, SWIR Raman imaging holds promise for rapid adoption by clinicians and biologists. This technique opens new possibilities for contrast agent-free visualization of pathophysiology in whole animals and intraoperative imaging in humans.Graphical abstract
Cross-modality representation and multi-sample integration of spatially resolved omics data
Authors: Li Zhen , Cui Xuejian , Chen Xiaoyang , Gao Zijing , Liu Yuyao , Pan Yan , Chen Shengquan , Lv Hairong , Zhai Lei , Jiang Rui 
Published: June 2024

AbstractSpatially resolved sequencing technologies have revolutionized our understanding of biological regulatory processes within the microenvironment by accessing the states of genomic regions, genes and proteins as well as spatial coordinates of cells. However, discrepancies between different modalities and samples hinder the analysis of spatial omics data, necessitating the development of advanced computational methods. In this article, we propose PRESENT, an effective and scalable contrastive learning framework, for the cross-modality representation and multi-sample integration of spatial multi-omics, epigenomics and transcriptomics data. Through comprehensive experiments on spatial datasets, PRESENT demonstrates superior performance across various species, tissues, and technologies. Specifically, PRESENT effectively integrates spatial dependency and omics information simultaneously, facilitating the detection of spatially functional domains and the exploration of biological regulatory mechanisms. Furthermore, PRESENT can be extended for the integrative analysis of tissue samples across different dissected regions or developmental stages, promoting the identification of hierarchical structures from systematic and spatiotemporal perspectives.
SAMPLE: an R package to estimate sampling effort for species’ occurrence rates
Authors: Bravo Henrique , Ben Chehida Yacine , van der Meij Sancia E.T. 
Published: June 2024

AbstractSpecies’ occurrence rates are the backbone of many ecological studies. Sampling of species occurrence, however, can come with challenges and might prove more difficult than anticipated. Logistical difficulties, limited funds or time, elusiveness or rarity of species and difficult sampling environments are all examples of scenarios that might contribute to (undesired) small sample sizes. In order to help circumvent some of these difficulties and uncertainties, we presentSAMPLE, anRpackage that aims to inform the user whether the amount of sampling conducted is enough to accurately estimate the occurrence rate of species. We use a simulation approach to help verify the accuracy of the package and to help guide the user in choosing the most appropriate values for the available parameters. Moreover, we provide a real data set where we usedSAMPLEto estimate the occurrence rate of various coral-dwelling species on their hosts and the minimum number of samples required for an accurate estimation. This provided example data set includes closely related host species, single or multiple symbionts on a single host coral taxon, and data points obtained from different depths to illustrate how occurrence rates can vary depending on the provided input. Due to its simplicity and easiness of use, this package allows for users to run it whilst in the field to estimate if sampling is sufficient or if the sampling approach needs to be adapted for a particular species. We hope that this package proves itself useful to users that need to estimate occurrence or prevalence rates of species and do not always have the possibility to obtain large sample sizes.
Proteolytic Performance is Dependent on Binding Efficiency, Processivity and Turnover: Single Protease Insights
Authors: Sørensen Emily Winther , Reinhold Freya Björk , Faber Andreas , Bender Steen , Kaestel-Hansen Jacob , de Sparra Lundin Jeannette , Voutyritsa Errika , Hedegaard Per , Christensen Sune M. , Hatzakis Nikos S. 
Published: June 2024

ABSTRACTProteases are essential enzymes for a plethora of biological processes and biotechnological applications, e.g., within the dairy, pharmaceutical, and detergent industries. Decoding the molecular level mechanisms that drive protease performance is key to designing improved biosolutions. However, direct dynamic assessment of the fundamental partial reactions of substrate binding and activity has proven a challenge with conventional ensemble approaches. We developed a single-molecule (SM) assay for the direct and parallel recording of the stochastic binding interaction of Savinase, a serine-type protease broadly employed in biotechnology, with casein synchronously with monitoring proteolytic degradation of the substrate. SM recordings enabled us to determine how the overall activity of Savinase and two mutants relies on binding efficiency, enzymatic turnover and activity per binding event. Analysis of residence times revealed three characteristic binding states. Mutations were found to dominantly alter the likelihood of sampling the long lived state, with lifetimes longer than 30 seconds, indicating this state contributes to overall activity and supporting a level of processivity for Savinase. This observation challenges conventional expectations, as the protease has no characterized substrate binding site, or binding domain, aside from the active site. These insights, inaccessible through conventional assays, offer new perspectives for engineering proteases with improved hydrolytic performance.
Prediction of gene cluster function based on transcriptional regulatory networks uncovers a novel locus required for desferrioxamine B biosynthesis
Authors: Augustijn Hannah E. , Reitz Zachary L. , Zhang Le , Boot Jeanine A. , Elsayed Somayah S. , Challis Gregory L. , Medema Marnix H. , van Wezel Gilles P. 
Published: June 2024

ABSTRACTBacteria produce a plethora of natural products that are in clinical, agricultural and biotechnological use. Genome mining revealed millions of biosynthetic gene clusters (BGCs) that encode their biosynthesis, and the major challenge is to predict the bioactivities of the molecules these BGCs specify, and how to elicit their expression. Here, we present an innovative strategy whereby we harness the power of regulatory networks combined with global gene expression patterns to predict BGC functions. Studying the regulon of iron master regulator DmdR1 inStreptomyces coelicolorcombined with co-expression data and large-scale comparative genome analysis identified the noveldesJGHgene cluster. Mutational and metabolomics analysis showed thatdesJGHis required for biosynthesis of the clinical drug desferrioxamine B. DesJGH thereby dictate the balance between the structurally distinct desferrioxamines B and E. We propose regulation-based genome mining as a promising approach to functionally prioritize BGCs to accelerate the discovery of novel bioactive molecules.
Tuning the stability of DNA tetrahedra with base-stacking interactions
Authors: Punnoose Jibin Abraham , Cole Dadrian , Melfi Tristan , Morya Vinod , Madhanagopal Bharath Raj , Chen Alan A. , Vangaveti Sweta , Chandrasekaran Arun Richard , Halvorsen Ken 
Published: June 2024

AbstractDNA nanotechnology relies on programmable anchoring of regions of single-stranded DNA through base pair hybridization to create nanoscale objects such as polyhedra, tubes, sheets, and other desired shapes. Recent work from our lab measured the energetics of base-stacking interactions and suggested that terminal stacking interactions between two adjacent strands could be an additional design parameter for DNA nanotechnology. Here, we explore that idea by creating DNA tetrahedra held together with sticky ends that contain identical base pairing interactions but different terminal stacking interactions. Testing all 16 possible combinations, we found that the melting temperature of DNA tetrahedra varied by up to 10 °C from altering a single base stack in the design. These results can inform stacking design to control DNA tetrahedra stability in a substantial and predictable way. To that end, we show that a 4 bp sticky end with weak terminal stacking does not form stable tetrahedra, while strengthening the stacks confers high stability with a 46.8 ± 1.2 °C melting temperature, comparable to a 6 bp sticky end with weak stacking (49.7 ± 2.9 °C). The results likely apply to other types of DNA nanostructures and suggest that terminal stacking interactions play an integral role in formation and stability of DNA nanostructures.
Monitoring macrophage polarization with gene expression reporters and bioluminescence phasor analysis
Authors: Tedeschi Giulia , Navarro Mariana X. , Scipioni Lorenzo , Sondhi Tanvi K. , Prescher Jennifer A. , Digman Michelle A. 
Published: June 2024

AbstractMacrophages exhibit a spectrum of behaviors upon activation and are generally classified as one of two types: inflammatory (M1) or anti-inflammatory (M2). Tracking these phenotypes in living cells can provide insight into immune function, but remains a challenging pursuit. Existing methods are mostly limited to static readouts or difficult to employ for multiplexed imaging in complex 3D environments while maintaining cellular resolution. We aimed to fill this void using bioluminescent technologies. Here we report genetically engineered luciferase reporters for long-term monitoring of macrophage polarization via spectral phasor analysis. M1- and M2-specific promoters were used to drive the expression of bioluminescent enzymes in macrophage cell lines. The readouts were multiplexed and discernable in both 2D and 3D formats with single cell resolution in living samples. Collectively, this work expands the toolbox of methods for monitoring macrophage polarization and provides a blueprint for monitoring other multifaceted networks in heterogeneous environments.
Generalization of the Packing Parameter for Quantifying the Morphology of Peptide Amphiphile Micelles
Authors: Kruse Luke E. , Ulery Bret D. , Hammond Karl D. 
Published: June 2024

AbstractWe present a quantitative means for classifying the shape of molecular dynamics simulated peptide amphiphile micelles (PAMs) that is both consistent with existing metrics and extendable to estimating shape-dependent free energy contributions. The presented framework not only outlines an approach for characterizing the shape of simulated PAMs but also presents expressions that can readily be applied to quantify the shape of particles from experimental techniques where aspect ratios are measured. The generalization of the packing parameter introduces a characteristic length that, when applied to simulated PAMs, functions intuitively as an effective radius for a PAM whose core is a perfect sphere or an infinite cylinder. The presented shape assignment scheme is used to develop a model for the free energy penalty associated with packing the tails of the amphiphiles into a core whose shape is modeled by an ellipsoid. Good agreement with previous models and scaling behaviors is observed and the importance of accounting for the shape and size dependence of the core is illustrated.TOC Graphic