bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between household context and emergency hospital use in older people: a retrospective cohort study on indicators for people living alone or living with somebody with frailty, developed from routine healthcare data in England
Authors: Lloyd Therese , Crellin Elizabeth , Brine Richard James , Shen Julia Y , Wolters Arne Timon 
Published: May 2022

ObjectivesTo derive two household context factors - living alone and living in a two-person household with a person who is frail - from routine administrative health data and to assess their association with emergency hospital use in people aged 65 or over.DesignRetrospective cohort study using national pseudonymised hospital data and pseudonymised address data derived from a minimised version of the Master Patient Index, a central database of all patient registrations in England.SettingEngland-wide.Participants4 876 285 people aged 65 years or older registered at GP practices in England on 16 December 2018 who were living alone or in a household of up to six people, and with at least one hospital admission in the last 3 years.OutcomesRates of accident and emergency (A&E) attendance and inpatient emergency admissions over a 1-year follow-up period.ResultsOlder people living alone had higher rates of A&E attendances (adjusted rate ratio 1.09, 95% CI 1.09 to 1.10) and emergency admissions (1.14, 95% CI 1.14 to 1.15) than older people living in households of 2–6 people. Older people living with someone with frailty in a two-person household had higher rates of A&E attendance (adjusted rate ratio 1.09, 95% CI 1.08 to 1.10) and emergency admissions (1.10, 95% CI 1.09 to 1.11) than other older people living in a two-person household.ConclusionsWe show that household context factors can be derived from linked routine administrative health data and that these are strongly associated with higher emergency hospital use in older people. Using household context factors can improve analyses, as well as support in the understanding of local population needs and in population health management.
mHealth apps delivering early intervention to support parents of children with autism: a scoping review protocol
Authors: Bharat Rahul , Uzaina Uzaina , Yadav Tribhuvanesh , Niranjan Sanjay , Kurade Palomi 
Published: May 2022

ObjectiveThis review aims to identify the mhealth apps delivering early intervention to support parents of children with autism spectrum disorders (ASD). We aim to explore the concept, context and methodology of implementation that is, theoretical framework, feasibility, quality of evidence, for such apps.BackgroundTo improve outcomes for children with autism, early intervention has been found to be promising. Parental training, parent psychoeducation and parent-mediated intervention are regarded as the gold standard, to achieve early childhood development goals. Digital health technologies like tele-health, web-based services, have been used to deliver this at a reduced cost. There is little evidence about their use and efficacy in empowering parents of children with ASD.Inclusion criteriaThe studies reporting the use of mhealth apps to support parents of children with ASD, in community settings, school settings, special schools, clinics, hospitals or child development centres. There will be no exclusion based on region, gender or sociocultural factors. The types of studies included will be quantitative, qualitative, mixed-methods study designs, case reports, grey literature, systematic reviews, clinical trials and studies reporting feasibility of digital mhealth applications.MethodUsing the NICE Healthcare Databases Advanced Search, we will search the following databases: MEDLINE, PUBMED, CINAHL, EMBASE, PsycINFO, Cochrane Library, EbscoHost, Sabinet, SAGE Journals, Directory of Open Access Journals, BioMed Central, Scopus, ScienceDirect. Furthermore, grey literature will be searched through Google Scholar, ShodhGanga, JSTOR, CORE, EBSCO, DOAJ, BASE. The searches will be limited to the age range of children between 2 and 6 years with ASD, and the date range is from the inception of the database to the current date. The terms for the ASD will be combined with terms for parent, early intervention and digital mhealth to identify eligible studies.
Mechanism and effects of artesunate on the liver function of rats with type 1 diabetic periodontitis
Authors: Bai Shuoqiu , Zhou Jingjing , Nong Xiaolin , Shi Rongkang , Yuan Zhong , Ma Chubin , Li Jiaquan 
Published: May 2022

Periodontitis is an inflammatory disease of the gums. Periodontitis in diabetic patients can aggravate insulin resistance; however, its molecular and biological mechanism remains unclear. This study aimed to explore the effects of diabetic periodontitis on liver function and determine the mechanism by which artesunate improves liver function. Rats with streptozotocin-induced diabetes were divided into five groups: normal control (NC), diabetic periodontitis (DM + PD), artesunate intervention (ART), insulin intervention (INS), and combined medication intervention (ART + INS) groups. Drug interventions were then administered to the rats in each group as follows: 50 mg/kg artesunate to the ART group, 6 U/kg insulin to the INS group, and 50 mg/kg artesunate + 6 U/kg insulin to the ART + INS group. Blood samples, liver tissues, and the maxillary alveolar bone were collected postsacrifice. ART was found to significantly ameliorate hyperglycemia, blood lipid concentrations, and liver function. The levels of inflammatory factors reduced; the effect was more pronounced in the ART + INS group. Artesunate presumably inhibits the TLR4/NF-κB signaling pathway and expression of downstream inflammatory factors, thereby exerting a protective effect on diabetes-related liver function. This offers a fresh approach to treat diabetes mellitus.
The effective potential of gluodynamics in the background of Polyakov loop and colormagnetic field
Authors: Bordag M. , Skalozub V. 
Published: May 2022

AbstractIn SU(N) gluodynamics, above the de-confinement temperature, the effective potential has minima at non-zero $$A_0$$

A
0

-background fields in the two-loop approximation. Also, it has a minimum at non-zero chromomagnetic background field, known as ’Savvidy’-vacuum, which shows up on the one-loop level. In this paper, we join these two approaches. We formulate, at finite temperature, the effective action, or the free energy, in SU(2) gluodynamics on the two-loop level, with both, $$A_0$$

A
0

background and magnetic background present at the same time, which was not done so far. We provide the necessary representations for both, effective numerical calculation and high-temperature expansions. The results are represented as a 3D plot of the real part of the effective potential. Also, we reproduce for zero either, the $$A_0$$

A
0

-background or the magnetic background, the known minima and compare them. The imaginary part is, on the two-loop level, still present. We mention that, as is known from literature for the case without $$A_0$$

A
0

-background, the imaginary part is compensated by the ring (’daisy’) diagrams. However, in our two-loop approximation, the results reveal an unnatural, singular behavior of the real part of the effective potential in the region, where the imaginary part sets in. Our conclusion is that one has to go beyond the two-loop approximation and its ring improved version, in order to investigate the minimum of the effective action as a function of $$A_0$$

A
0

and chromomagnetic field, and its stability, at least in the approximation of super daisy diagrams, i.e., the Hartree approximation in the CJT formalism.
Analysis of Evolved Response Thresholds for Decentralized Dynamic Task Allocation
Authors: Mathias H. David , Wu Annie S. , Dang Daniel 
Published: May 2022

In this work, we investigate the application of a multi-objective genetic algorithm to the problem of task allocation in a self-organizing, decentralized, threshold-based swarm. We use a multi-objective genetic algorithm to evolve response thresholds for a simulated swarm engaged in dynamic task allocation problems: two-dimensional and three-dimensional collective tracking. We show that evolved thresholds not only outperform uniformly distributed thresholds and dynamic thresholds but achieve nearly optimal performance on a variety of tracking problem instances (target paths). More importantly, we demonstrate that thresholds evolved for some problem instances generalize to all other problem instances, eliminating the need to evolve new thresholds for each problem instance to be solved. We analyze the properties that allow these paths to serve asuniversal training instancesand show that they are quite natural.Aftera priorievolution, the response thresholds in our system are static. The problem instances solved by the swarms are highly dynamic, with schedules of task demands that change over time with significant differences in rate and magnitude of change. That the swarm is able to achieve nearly optimal results refutes the common assumption that a swarm must be dynamic to perform well in a dynamic environment.
Precision Probiotic Medicine to Improve ICB Immunotherapy
Authors: Di Luccia Blanda , Colonna Marco 
Published: May 2022

Summary:
The established impact of gut microbiota- and probiotic-derived metabolites on immune-checkpoint blockade (ICB) has spurred extensive efforts to identify strains and druggable bioactive molecules of microbial origin that can improve tumor immune therapy. In this issue, Kawanabe-Matsuda and colleagues show that the exopolysaccharide EPS-R1 produced by the probiotic strain Lactobacillus delbrueckii subsp. bulgaricus augments the response to ICB therapy by expanding the population of Peyer's patches CCR6+ CD8+ T cells, which can subsequently migrate from the gut into CCL20-expressing tumors to enhance antitumor activity.
See related article by Kawanabe-Matsuda et al., p. 1336 (10).
Abstract 121: Exploiting Natural Genetic Variation In The Human Triglyceride Regulator
APOA5
To Understand Its Function
Authors: Stankov Sylvia , Vitali Cecilia , Park Joseph , Nguyen David , Englander S. Walter , Phillips Michael C , Hand Nicholas J , Rader Daniel J 
Published: May 2022

Plasma triglycerides (TGs) are an independent predictor of the risk for CAD, the leading cause of death worldwide. TGs are also positively associated with risk and severity of hyperTG-induced acute pancreatitis (HTG-AP). Current therapies are often insufficient in reducing extremely elevated TGs. We believe that apolipoprotein A-V (apoA-V, encoded by APOA5) can fill this unmet medical need. ApoA-V is a potent modulator of TG metabolism; it enhances lipoprotein lipase TG hydrolysis. We hypothesize that naturally occurring human APOA5 variants can inform ApoA-V function and identify novel ApoA-V based therapeutic axes.
We used the Penn Medicine Biobank (PMBB) to identify and measure plasma TGs of carriers of APOA5 variants predicted to change ApoA-V structure-function. Then, we used hydrogen-deuterium exchange mass spectroscopy to determine the secondary structure of ApoA-V, thereby identifying putative functional domains onto which we mapped our variants of interest. Finally, we characterized the plasma lipid effects of these mutants using adeno-associated viral (AAV) vectors in apoa5 knockout (KO) mice.
We identified APOA5 variants associated with changes in plasma TGs. These variants primarily fall near the central heparin binding domain or C-terminal lipid binding domain. We selected APOA5 Q275X, which removes the entire lipid binding domain, for further interrogation. Apoa5 KO mice that received APOA5 Q275X AAV had higher plasma TGs than mice treated with WT APOA5 AAV. While WT ApoA-V protein associated with VLDL and HDL particles, Q275X ApoA-V protein appeared in lipoprotein free fractions.
We have identified APOA5 variants associated with plasma TG phenotypes in humans, and mapped them to an experimentally determined ApoA-V secondary structure to identify the functional domains likely impacted. We have identified APOA5 Q275X as a loss of function variant that fails to bind lipoprotein particles and is associated with elevated plasma TGs. Continued study of this and other interesting naturally occurring variants will provide insight into the function of ApoA-V in TG metabolism. These insights can help us to therapeutically enhance ApoA-V to rapidly reduce TG levels during acute HTG-AP and to help prevent recurrent HTG-AP.
Abstract P141: Downregulation Of Deletion Variants Of Telomerase Reverse Transcriptase (TERT) By Transforming Growth Factor-β1-silencing Decreases Mitochondrial ROS In Diabetic CD34
+
Cells
Authors: Jahan Jesmin , Montes de Oca Ildamaris , Maghrabi Ahmad , Lopez-Yang Christine , Beyer Andreas M , Garcia Charles , Jarajapu Yagna P 
Published: May 2022

Telomerase reverse transcriptase (TERT) modulates mitochondrial levels of reactive oxygen species (mitoROS). Deletion variants, α-, β- and αβ, are negative regulators of TERT. Increased ROS levels in diabetic CD34
+
cells impair vasoreparative functions. Our recent studies showed that silencing of transforming growth factor-β1 (TGF-β1) decreased ROS levels and stimulated vasoreparative functions. This study tested the hypothesis that prevalence of TERT deletion variants is higher in diabetic CD34
+
cells and that TGF-β1-silencing decreases mitoROS by downregulation of the variants.

CD34
+
cells derived from either male or female nondiabetic (ND) (n=38) or diabetic (DB), both type 1 and type 2, (n=43) subjects were studied. Phosphorodiamidate morpholino oligomers (PMO) were used for TGF-β1-silencing. TERT variants were characterized by qPCR and agarose gel electrophoresis. MitoSOX-flow cytometry and ELISA were used for determining mitoROS levels and telomerase activity, respectively.

TGF-β1-silencing decreased mitoROS levels in DB-CD34+ cells (P<0.01 vs ND-cells, n=6). This effect was reversed by TERT inhibitor, BIBR1532 (1μM) (n=6) or mito-X-TERT, a decoy peptide that prevents mitochondrial translocation of TERT (n=5). TERT expression was higher in DB compared to ND cells (P<0.05, n=18) but telomerase activity was lower (P<0.05 vs ND, n=10). Prevalence of TERT deletion variants was higher among DB cells compared to ND (DB - 8/10 vs ND - 2/10 subjects have one or more of α, β, or αβ variants). TGF-β1-silencing downregulated the expression of TERT variants and increased full-length TERT that was accompanied by increased telomerase activity in DB-CD34+ cells (P<0.05 vs untreated, n=5).
This study suggests that diabetes is associated with higher prevalence of TERT variants that would impede mitochondrial functions of TERT. TGF-β1-silencing decreases mitoROS levels at least in part by downregulation of TERT variants.
Abstract P175:
In Vitro
Cholesterol Treatment Does Not Reproduce Smooth Muscle Cell Phenotypic Plasticity Observed
In Vivo
Authors: Conklin Austin , Schlamp Florencia , Ord Tiit , Kaikkonen Minna U , Fisher Edward , Romanoski Casey E 
Published: May 2022

Vascular Smooth Muscle Cells (SMCs) exhibit a significant degree of phenotypic plasticity in atherosclerotic lesions. Previously, this phenotypic plasticity, and specifically the re-differentiation of SMCs into macrophages, has been modeled in vitro using cholesterol treatment. We performed a meta-analysis of five different murine SMC lineage tracing single-cell RNA sequencing (scRNA-seq) experiments performed by four different research groups; we identified 24 different cell types and find considerable differences in the proportion of recovered normal ‘contractile’ SMCs and SMC-derived macrophages between experiments.
In addition, we performed bulk RNA-seq on cultured murine SMCs with and without cholesterol treatment for 0, 24, or 48 hours. We find that cholesterol treatment regulates transcripts associated with the induction of the unfolded protein response, reduction of cholesterol biosynthesis, and reduction in cell proliferation. Additionally, chromatin immunoprecipitation followed by high-throughput sequencing for H3K27ac performed on in vitro SMCs treated and untreated for 0, 24, or 48 hours reveals that AP-1 and ATF4 binding motifs are found more frequently at cholesterol treatment specific H3K27ac chromatin sites.
Finally, we compared transcriptomic data between in vivo vascular cell types identified in our meta-analysis and in vitro SMCs. We additionally included scRNA-seq data and microarray data collected for in vitro SMCs and bulk RNA-seq data collected for M1, M2, and oxLDL treated macrophages. We find that compared to the phenotypic plasticity observed in vivo, cholesterol exhibits modest effects on the transcriptomes of in vitro SMCs and does not reproduce the changes observed in vivo, while in vitro macrophages, especially oxLDL treated macrophages, more closely approximate their in vivo counterparts.
We conclude that differences between SMC lineage-tracing scRNA-seq experiments obscures the degree to which SMC-derived macrophages are present in murine atherosclerotic plaques, that cholesterol has modest effects on in vitro SMC transcriptomes, and that the effects of cholesterol do not reproduce the phenotypic plasticity observed in vivo.
Implementation of an Appointment‐Based Cardiac Rehabilitation Approach: A Single‐Center Experience
Authors: Wright Catherine X. , Fournier Sean , Deng Yanhong , Meng Can , Hiller Susan , Oen‐Hsiao Joyce M. , Dreyer Rachel P. 
Published: May 2022

Background
There has been a focus on alternative cardiac rehabilitation (CR) delivery models aimed at improving CR adherence and completion. We examined pre‐ and post‐CR health outcomes, reasons for discharge, and predictors of completion using a patient‐driven appointment‐based CR approach that uses center‐scheduled class start times.

Methods and Results

Data were used from an urban single‐center CR program at Yale New Haven Health (2012–2017) that enrolled 2135 patients. We evaluated pre‐ and post‐CR outcomes (12 weeks) using paired
t
tests and used a multivariable logistic regression model to examine predictors of CR completion (≥36 sessions) for the overall cardiovascular disease population. The mean age of participants was 65±12 years, 27.9% were women, and 5.1% were Black patients, and patients completed a median of 30 of 36 sessions. Patients achieved significant improvements in health outcomes, including across age and sex subgroups. The primary reason for discharge was completion of all 36 sessions of CR (46.4%). The final logistic regression model contained 12 predictors: age, sex, Black race, marital status, employment, number of physician‐reported risk factors, dietary fat intake >30%, obesity, lack of exercise, benign prostatic hyperplasia, and self‐reported stress and physical activity.

Conclusions
We demonstrated that patients participating in an appointment‐based CR program achieved significant improvements in health outcomes and across sex/age subgroups. In addition, older individuals were more likely to complete CR. An appointment‐based approach could be a viable alternative CR method to aid in optimizing the dose‐response benefit of CR for patients with cardiovascular disease.
Left Atrial Remodeling and Stroke in Patients With Sinus Rhythm and Normal Ejection Fraction: ARIC‐NCS
Authors: Bianco Francesco , De Caterina Raffaele , Chandra Alvin , Aquila Iolanda , Claggett Brian , Johansen Michelle C. , Gonçalves Alexandra , Norby Faye L. , Cogswell Rebecca , Soliman Elsayed Z. , Gottesman Rebecca , Mosley Thomas , Alonso Alvaro , Shah Amil , Solomon Scott D. , Chen Lin Yee 
Published: May 2022

Background
Age‐related left atrial (LA) structural and functional abnormalities may be related to subclinical cerebral infarcts (SCIs) and stroke. We evaluated the association of 3‐dimensional echocardiographic LA contractility parameters with SCIs and stroke across the spectrum of tertiles of age increment in elderly patients with sinus rhythm, normal ejection fraction, and no history of atrial fibrillation.

Methods and Results

We enrolled 407 participants (mean age, 76±8 years; 40% men) from ARIC‐NCS (Atherosclerosis Risk in Communities Neurocognitive Study) undergoing a brain magnetic resonance imaging and 3‐dimensional echocardiographic examinations in 2011 to 2013. The sample was analyzed among age tertiles and subgroups: no cerebral magnetic resonance imaging–detectable infarcts (n=315), magnetic resonance imaging–diagnosed SCIs (n=58), and clinically diagnosed stroke (n=34). The frequency of SCIs significantly increased over age tertiles (
P
trend 0.023). LA global longitudinal strain—a 3‐dimensional echocardiographic index of LA reservoir function—and E/e’ divided by LA global longitudinal strain—an index of LA stiffness—worsened across age tertiles (
P
trend 0.014 and 0.001, respectively), and only in the categories of SCIs (
P
trend <0.001 and 0.045, respectively) and stroke (
P
trend 0.001 and 0.011, respectively). LA global longitudinal strain was negatively associated with increased odds of SCIs (
P
=0.036,
P
=0.008, and
P
=0.001, respectively) and strokes (
P
=0.043,
P
=0.015, and
P
=0.001, respectively) over age tertiles, with a significant interaction between age tertiles (interaction
P
=0.043 and
P
=0.010, respectively). E/e’ divided by LA global longitudinal strain was positively associated with the presence of SCIs (
P
=0.037,
P
=0.007, and
P
=0.001, respectively) and strokes (
P
=0.045,
P
=0.007, and
P
=0.003, respectively) over age tertiles, with a significant interaction only for SCIs (interaction
P
=0.040) and not for clinical stroke.

Conclusions
In a large cohort study of elderly patients, among participants with sinus rhythm, normal ejection fraction, and no history of atrial fibrillation, measures of worse age‐related LA reservoir function and stiffness are associated with higher odds of SCIs and stroke.