bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intermittent hypoxia increased the expression of ESM1 and ICAM‐1 in vascular endothelial cells via the downregulation of microRNA‐181a1
Authors: Takasawa Shin , Makino Mai , Yamauchi Akiyo , Sakuramoto‐Tsuchida Sumiyo , Hirota Rina , Fujii Ryusei , Asai Keito , Takeda Yoshinori , Uchiyama Tomoko , Shobatake Ryogo , Ota Hiroyo 
Published: November 2023

AbstractSleep apnea syndrome (SAS) exposes cells throughout the body to intermittent hypoxia (IH). Intermittent hypoxia is a risk factor not only for hypertension and insulin resistance but also for vascular dysfunction. We have reported correlations between IH, insulin resistance and hypertension. However, the details of why IH leads to vascular dysfunction remain unclear. In this study, we investigated inflammation‐related transcripts in vascular endothelial cells (human HUEhT‐1 and mouse UV2) exposed to IH by real‐time RT‐PCR and found that intercellular adhesion molecule‐1 (ICAM‐1) and endothelial cell‐specific molecule‐1 (ESM1) mRNAs were significantly increased. ELISA confirmed that, in the UV2 cell medium, ICAM‐1 and ESM1 were significantly increased by IH. However, the promoter activities of ICAM‐1 and ESM1 were not upregulated. On the other hand, IH treatment significantly decreased microRNA (miR)‐181a1 in IH‐treated cells. The introduction of miR‐181a1 mimic but not miR‐181a1 mimic NC abolished the IH‐induced upregulation of Ican‐1 and ESM1. These results indicated that ICAM‐1 and ESM1 were upregulated by IH via the IH‐induced downregulation of miR‐181a1 in vascular endothelial cells and suggested that SAS patients developed atherosclerosis via the IH‐induced upregulation of ICAM‐1 and ESM1.
Money Makes the World Go Round: How Much Difference Do Recovery and Resilience Plans Make to EU Reform Governance?
Authors: Miró Joan , Natili Marcello , Schelkle Waltraud 
Published: November 2023

AbstractThe Next Generation EU (NGEU) package transformed European economic governance. This article examines the implications of this change in terms of EU polity formation and in terms of social policy content. It asks whether the temporary availability of large funds increases the leverage of the Commission in the European Semester and how this innovation affects sensitive policies. In the tradition of Stein Rokkan, the article advances a conception of the EU as a compound polity that needs to reconcile dispersed authority with second‐order loyalty. We then contrast our theoretical expectations with traditional reform surveillance and experimentalist governance theories. The drafting of Recovery and Resilience Plans for Italy and Spain provides the empirical basis for assessing these expectations. The analysis shows a dual effect: adding fiscal capacity to the European Semester enhances the Commission's hierarchical power whilst the need to ensure member states' loyalty leaves room for national executives to insist on their priorities.
Sexual Minorities, Religion, and Self‐Rated Health in the United States
Authors: Cranney Stephen 
Published: November 2023

AbstractWhile religiosity has generally been found to be associated with health, sexual minority individuals are a theoretically unique population in the literature. Because of sample size issues, the extent to which sexual minority individuals differ from nonsexual minority individuals in the health and religion relationship has been difficult to comprehensively test; additionally, the theoretically germane but often hypothesized distinction between affirming and nonaffirming religions has remained largely untested. This study draws on the Cooperative Election Study, a nationally representative survey with a relatively large sexual minority sample (∼6600), and finds that (1) sexual minority individuals are less likely to affiliate with a religion; (2) sexual minority individuals report poorer health; (3) sexual minority individuals do enjoy an overall health benefit from religiosity, but this benefit is attenuated (compared to nonsexual minority individuals) in the case of affiliation; and (4) there is some ambiguous evidence for an affirming religiosity effect.
Ontological unpredictability: what can realists say about unpredictability, contingency and catastrophe?
Authors: Al‐Amoudi Ismael 
Published: November 2023

AbstractThis paper introduces the original research articles that constitute the present Forum issue on unpredictability, contingency and catastrophe. In doing so, it also identifies and discusses the specificity of realist approaches to the above questions. It is argued that attentiveness to the ontological dimension of (un)predictability opens promising avenues for reflexive approaches to social science and collective action.
Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high‐dose GLP‐1 receptor agonists and GLP‐1 receptor‐based co‐agonists
Authors: Goldenberg Ronald M. , Gilbert Jeremy D. , Manjoo Priya , Pedersen Sue D. , Woo Vincent C. , Lovshin Julie A. 
Published: November 2023

SummaryType 2 diabetes (T2D), obesity, and nonalcoholic fatty liver disease/nonalacoholic steatohepatitis (NAFLD/NASH) share mutual causalities. Medications that may offer clinical benefits to all three conditions are being developed. Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are approved for the management of T2D and obesity and there is great interest in evaluating higher doses of available GLP‐1RAs and developing novel GLP‐1RA‐based co‐agonists to provide greater reductions in glycated hemoglobin (HbA1c) and body weight as well as modifying NAFLD/NASH complications in clinically meaningful ways. High‐dose GLP‐1RAs and multi‐hormonal strategies including GLP‐1R agonism have either already been approved or are in development for managing T2D, obesity, or NASH. We provide a mechanistic outline with a detailed summary of the available clinical data and ongoing trials that are adjudicating the impact of high‐dose GLP‐1RAs, unimolecular, and multimolecular GLP‐1R‐based co‐agonists in populations living with T2D, obesity, or NASH. The available trial findings are aligned with preclinical observations, showing clinical efficacy and safety thus providing optimism for the expansion of GLP‐1R‐based drug classes for managing the triad of T2D, obesity and NASH. Development, access, and wide‐spread utilization of these new therapeutic approaches will offer important opportunities to markedly improve the collective global burden of T2D, obesity, and NASH.
Comparison of very high‐power short‐duration, high‐power short‐duration, and low‐power long‐duration radiofrequency ablation for atrial fibrillation: A systematic review and network meta‐analysis
Authors: Junarta Joey , Rodriguez Sebastian , Ullah Waqas , Siddiqui Muhammad U. , Riley Joshua M. , Patel Anjani , O'Neill Parker , Dikdan Sean J. , Fradin James J. , Rosen Jake L. , Frisch Daniel R. 
Published: November 2023

AbstractBackgroundThe optimal power and duration settings for radiofrequency (RF) atrial fibrillation (AF) ablation to improve efficacy and safety is unclear. We compared low‐power long‐duration (LPLD), high‐power short‐duration (HPSD), and very HPSD (vHPSD) RF settings for AF ablation.MethodsThis network meta‐analysis (NMA) was structured according to the Preferred Reporting Items for Systematic Review and Meta‐Analyses guidelines. Medline, Scopus and Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies. Observational and randomized studies were included. Eligible studies compared outcomes in AF patients who underwent first‐time RF ablation with the following settings: vHPSD (70–90 W, 3–10 s), HPSD (45–60 W, 5–10 s), or LPLD (20–40 W, 20–60 s).ResultsThirty‐six studies comprising 10,375 patients were included (33% female). Frequentist NMA showed LPLD tended toward a lower odds of freedom from arrhythmia (FFA) versus HPSD (OR 0.93, 95% CI 0.86–1.00). There was no difference in FFA between vHPSD versus HPSD. Splitwise interval estimates showed a lower odds of FFA in LPLD versus vHPSD on direct (OR 0.78, 95% CI 0.65–0.93) and network estimates (OR 0.85, 95% CI 0.73–0.98). Frequentist NMA showed less total procedural (TP) time with HPSD versus LPLD (generic variance 1.06, 95% CI 0.83 to 1.29) and no difference between HPSD versus vHPSD.ConclusionThis NMA shows improved procedural times in HPSD and vHPSD versus LPLD. Although HPSD tended toward improved odds of FFA compared to LPLD, the overall result was not statistically significant. The odds of FFA in LPLD was lower versus vHPSD on direct and network estimates on splitwise interval analysis. Large prospective head‐to‐head randomized trials are needed to validate HPSD and vHPSD settings.
History of multifetal gestation and long‐term maternal mortality
Authors: Mitro Susanna D. , Sundaram Rajeshwari , Qiao Yan , Gleason Jessica L. , Yeung Edwina , Hinkle Stefanie N. , Mendola Pauline , Mills James L. , Grandi Sonia M. , Mumford Sunni L. , Schisterman Enrique F. , Zhang Cuilin , Grantz Katherine L. 
Published: November 2023

AbstractBackgroundMultifetal gestation could be associated with higher long‐term maternal mortality because it increases the risk of pregnancy complications such as preeclampsia and preterm birth, which are in turn linked to postpartum cardiovascular risk.ObjectivesWe examined whether spontaneously conceived multifetal versus singleton gestation was associated with long‐term maternal mortality in a racially diverse U.S. cohort.MethodsWe ascertained vital status as of 2016 via linkage to the National Death Index and Social Security Death Master File of 44,174 mothers from the Collaborative Perinatal Project (CPP; 1959–1966). Cox proportional hazards models with maternal age as the time scale assessed associations between history of spontaneous multifetal gestation (in the last CPP observed pregnancy or prior pregnancy) and all‐cause and cardiovascular mortality, adjusted for demographics, smoking status, and preexisting medical conditions. We calculated hazard ratios (HR) for all‐cause and cause‐specific mortality over the study period and until age 50, 60, and 70 years (premature mortality).ResultsOf eligible participants, 1672 (3.8%) had a history of multifetal gestation. Participants with versus without a history of multifetal gestation were older, more likely to have a preexisting condition, and more likely to smoke. By 2016, 51% of participants with and 38% of participants without a history of multifetal gestation had died (unadjusted all‐cause HR 1.14, 95% confidence interval [CI] 1.07, 1.23). After adjustment for smoking and preexisting conditions, a history of multifetal gestation was not associated with all‐cause (adjusted HR 1.00, 95% CI 0.93, 1.08) or cardiovascular mortality (adjusted HR 0.99, 95% CI 0.87, 1.11) over the study period. However, history of multifetal gestation was associated with an 11% lower risk of premature all‐cause mortality (adjusted HR 0.89, 95% CI 0.82, 0.96).ConclusionsIn a cohort with over 50 years of follow‐up, history of multifetal gestation was not associated with all‐cause mortality, but may be associated with a lower risk of premature mortality.
Past the saturation point: Why voters switch from mainstream to niche parties and vice‐versa
Authors: van de Wardt Marc , Rooduijn Matthijs 
Published: November 2023

AbstractWhen do voters switch from mainstream to niche parties and vice‐versa? To understand these switches, we focus on the saturation of the party system. We theorize that when a party system is oversaturated – i.e. when a higher effective number of parties contests elections than predicted based on socio‐political contextual characteristics (the system's ‘carrying capacity’) – it becomes increasingly likely that: (1) mainstream party voters defect to niche parties; and (2) niche party voters refrain from switching to mainstream parties. Based on vote‐switching patterns in 15 countries and 53 elections, we find that oversaturation increases shifts from mainstream to niche parties. Further analyses show that this holds for shifts from mainstream to radical left and right parties, but not for shifts to green parties. This has important consequences for research on vote switching, the electoral consequences of policy differentiation and the competition between niche and mainstream parties.
An improved hierarchical clustering method based on the k‐NN and density peak clustering
Authors: Shi Zhicheng , Guo Renzhong , Zhao Zhigang 
Published: November 2023

AbstractClustering is one of the most prevalent and important data mining algorithms ever developed. Currently, most clustering methods are divided into distance‐based and density‐based. In 2014, the fast search and find of density peaks clustering method was proposed, which is simple and effective and has been extensively applied in several research domains. However, the original version requires manually assigning a cut‐off distance and selecting core points. Therefore, this article improves the density peak clustering method from two aspects. First, the Gaussian kernel is substituted with a k‐nearest neighbors method to calculate local density. This is important as compared with selecting a cut‐off distance, calculating the k‐value is easier. Second, the core points are automatically selected, unlike the original method that manually selects the core points regarding local density and distance distribution. Given that users' selection influences the clustering result, the proposed automatic core point selection strategy overcomes the human interference problem. Additionally, in the clustering process, the proposed method reduces the influence of manually assigned parameters.
3D Printed Bioinspired Hierarchical Surface Structure With Tunable Wettability
Authors: Rahman M. M. Towfiqur , Joyee Erina Baynojir 
Published: November 2023

Abstract
Nature has examples of impressive surfaces and interfaces with diverse wettability stemming from superhydrophilicity to superhydrophobicity. The multiscale surface structures found in biological systems generally have high geometric complexity, which makes it challenging to replicate their characteristics, especially using traditional fabrication techniques. It is even more challenging to fabricate such complex microstructures with tunable wettability. In this paper, we propose a method to tune the wettability of a microscale surface by changing the geometrical parameters of embedded microstructures in the surface. By taking inspiration from an insect (springtails), we designed micropillar arrays with different roughness by adjusting geometric parameters such as reentrant angle, pitch distance, and the number of spikes and pillars. This study shows that, by changing geometrical parameters in microscale, the apparent contact angle, and hence the surface wettability can be calibrated. The microscale pillars were fabricated using a precise microdirect light processing (μDLP) three-dimensional (3D) printer. Different printing parameters were studied to optimize the geometric parameters to fabricate 3D hierarchical structures with high accuracy and resolution. The largest apparent contact angle in our experiments is up to 160 deg, with pillars of 0.17 mm height and 0.5 mm diameter, 55 deg reentrant angle, and a spacing of 0.36 mm between pillars. The lowest contact angle is ∼35 deg by reducing the pillar size and spacing. By controlling the size of different features of the pillar, pillar number, and layout of the mushroom-shaped micropillars, the wettability of the surface is possible to be tuned from a highly nonwetting liquid/material combination to highly wetting material. Such wettability tuning capability expands the design space for many biomedical and thermofluidic applications.
Estimating the Thermal Conductivity of Thin Films: A Novel Approach Using the Transient Plane Source Method
Authors: Landry David , Flores Renzo , Goodman Renée B. 
Published: November 2023

Abstract
The conventional transient plane source (TPS) method for thin films is used for films and adhesives with thicknesses between 50 and 200 μm. Measurements with the conventional TPS method are usually inaccurate due to thermal contact resistance between the insulating sensor layers, the film and the sensor, and the film and the background material. A new approach to measuring thin films with the TPS is introduced, where the heat flow is constrained to one dimension, and a slab layer made from the same background material is introduced between the thin film and the TPS sensor. This decouples the effects of the thermal contact resistance (TCR) of the sensor to the thermal resistance of the film. The new approach is tested on four different thin films with stainless steel as the background material. The results are compared to guarded heat flowmeter measurements. Excellent agreement (&lt; 12% error) between the two methods is achieved, showing that the new method proposed is fast, accurate, and convenient alternative for determining the thermal conductivity of thin films.
In vitro
and
in vivo
activity of cefiderocol against
Achromobacter
spp. and
Burkholderia cepacia
complex, including carbapenem-non-susceptible isolates
Authors: Takemura Miki , Nakamura Rio , Ota Merime , Nakai Ryuichiro , Sahm Daniel F. , Hackel Meredith A. , Yamano Yoshinori 
Published: November 2023

ABSTRACT

Achromobacter
spp. and
Burkholderia cepacia
complex (Bcc) are rare but diverse opportunistic pathogens associated with serious infections, which are often multidrug resistant. This study compared the
in vitro
antibacterial activity of the siderophore antibiotic cefiderocol against
Achromobacter
spp. and Bcc isolates with that of other approved antibacterial drugs, including ceftazidime-avibactam, ciprofloxacin, colistin, imipenem-relebactam, and meropenem-vaborbactam. Isolates were collected in the SIDERO multinational surveillance program. Among 334
Achromobacter
spp. isolates [76.6% from respiratory tract infections (RTIs)], cefiderocol had minimum inhibitory concentration (MIC)
50/90
of 0.06/0.5 µg/mL overall and 0.5/4 µg/mL against 52 (15.6%) carbapenem-non-susceptible (Carb-NS) isolates. Eleven (3.3%)
Achromobacter
spp. isolates overall and 6 (11.5%) Carb-NS isolates were not susceptible to cefiderocol. Among 425 Bcc isolates (73.4% from RTIs), cefiderocol had MIC
50/90
of ≤0.03/0.5 µg/mL overall and ≤0.03/1 µg/mL against 184 (43.3%) Carb-NS isolates. Twenty-two (5.2%) Bcc isolates overall and 13 (7.1%) Carb-NS isolates were not susceptible to cefiderocol. Cumulative MIC distributions showed cefiderocol to be the most active of the agents tested
in vitro
against both
Achromobacter
spp. and Bcc. In a neutropenic murine lung infection model and a humanized pharmacokinetic immunocompetent rat lung infection model, cefiderocol showed significant bactericidal activity against two meropenem-resistant
Achromobacter xylosoxidans
strains compared with untreated controls (
P
< 0.05) and vehicle-treated controls (
P
< 0.05), respectively. Meropenem, piperacillin-tazobactam, ceftazidime, and ciprofloxacin comparators showed no significant activity in these models. The results suggest that cefiderocol could be a possible treatment option for RTIs caused by
Achromobacter
spp. and Bcc.
Safety, tolerability, and pharmacokinetics of ibrexafungerp in healthy Chinese subjects: a randomized, double-blind, placebo-controlled phase 1 trial
Authors: Liu Xiaoyan , Zhang Rui , Li Rong , Wu Qiong , Pan Chao , Yu Xiangqing , Liu Yuhui , Wang Benjie , Yu Shuwen 
Published: November 2023

ABSTRACT

Ibrexafungerp (code name in China: HS-10366) is a first-in-class and orally active triterpenoid antifungal agent with broad antifungal activity against
Candida
spp.,
Aspergillus
spp., and other fungal pathogens. It was approved by the U.S. Food and Drug Administration for the treatment of vulvovaginal candidiasis. The study aimed to evaluate the safety, tolerability, and pharmacokinetic (PK) characteristics of oral ibrexafungerp in healthy Chinese adults. A single-center, randomized, double-blind, placebo-controlled single ascending dose (SAD,
n
= 42), and multiple ascending dose (MAD,
n
= 28) study was conducted in healthy Chinese subjects from March to October 2022. There were three cohorts in the SAD stage (300, 600, and 1,500 mg) and two cohorts in the MAD stage [450 mg once daily (QD) for 7 days; a loading dose of 750 mg twice daily (BID) for the first 2 days followed by a maintenance dose of 750 mg QD for consecutive 5 days]. Eligible participants in each cohort were randomly assigned in a 6:1 ratio to receive either ibrexafungerp or placebo orally. The primary objectives were to evaluate the safety and tolerability. The secondary objective was to evaluate PK parameters, including C
max
, AUC, and t
1/2
. A total of 70 healthy Chinese subjects were enrolled in the study. The mean (SD) age was 29.0 (6.32), and 55.7% were male. All treatment-emergent adverse events (TEAEs) were mild or moderate. There were no serious adverse events, and no subjects were discontinued from the study due to TEAEs. All TEAEs were recovered or resolved. The most common TEAEs were diarrhea, abdominal pain, and nausea. In the SAD stage, C
max
, and AUC increased in an approximately dose-proportional manner in the dose range of 300–1,500 mg. The mean t
1/2
was within 18.29–21.30 hours. In the MAD stage, an accumulation of exposure (C
max
and AUC) was observed following multiple doses. This phase 1 study demonstrates a favorable safety, tolerability, and PK profile of ibrexafungerp in healthy Chinese subjects.
No fitness cost entailed by type VI secretion system synthesis, assembly, contraction, or disassembly in enteroaggregative
Escherichia coli
Authors: Taillefer Boris , Giraud Julien F. , Cascales Eric 
Published: November 2023

ABSTRACT

Polymicrobial communities are shaped by beneficial and antagonistic interactions between the different species. One of the key players for competition is the type VI secretion system, a large multiprotein complex that assembles a contractile tail-like structure spanning the entire cytoplasm. This contractile tail is comprised of an inner tube tipped by a puncturing complex and wrapped by a sheath that polymerizes under an extended conformation. Contraction of the sheath propels the needle-like tube complex toward the target cell where it delivers effectors. The ClpV AAA
+
ATPase is then recruited to the contracted sheath and uses the energy of ATP hydrolysis for its disassembly. Due to the size of the apparatus and its mechanism of disassembly, it is thought that the T6SS mechanism of action is costly for the cell, and hence can significantly impact its fitness. By using enteroaggregative
Escherichia coli
strains in which the T6SS is arrested at different stages of its mechanism of action, we show here that there is no significant cost associated with T6SS synthesis, assembly, contraction, or disassembly
in vitro
.

IMPORTANCE

Bacteria use weapons to deliver effectors into target cells. One of these weapons, the type VI secretion system (T6SS), assembles a contractile tail acting as a spring to propel a toxin-loaded needle. Due to its size and mechanism of action, the T6SS was intuitively thought to be energetically costly. Here, using a combination of mutants and growth measurements in liquid medium, on plates, and in competition experiments, we show that the T6SS does not entail a growth cost to enteroaggregative
Escherichia coli
.