bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting histamine receptor 4 in cholinergic urticaria with izuforant (LEO 152020): results from a phase IIa randomized double-blind placebo-controlled multicentre crossover trial
Authors: Grekowitz Eva , Metz Martin , Altrichter Sabine , Bauer Andrea , Brockow Knut , Heine Guido , Lionnet Leonard , Saday Kadriye Kaplan , Hultsch Thomas , Søerensen Ole E , Maurer Marcus 
Published: February 2024

Abstract

Background
Cholinergic urticaria (CholU) is a common subtype of chronic inducible urticaria, where signs and symptoms (e.g. pruritic wheals and angioedema) are triggered by sweating due to physical exercise, passive warming and by other sweat-inducing situations. While guidelines recommend treatment with second-generation H1 antihistamines, approximately 90% of patients report uncontrolled disease. Targeting the histamine 4 receptor (H4R) has shown promise in preclinical/clinical studies of allergic/inflammatory diseases. Izuforant (LEO 152020) is a selective oral H4R antagonist with expected dual antipruritic and anti-inflammatory effects.

Objectives
To assess the effects of izuforant in adults with CholU, a common type of chronic urticaria driven by histamine and characterized by high skin levels of H4R expression.

Methods
This was a phase IIa randomized double-blind placebo-controlled multicentre crossover trial where patients with CholU with an inadequate response to ≥ 1 standard dose of H1 antihistamine received izuforant 100 mg twice daily or placebo (EUCTR2020-004961-38-DE; NCT04853992). The primary endpoint was change from baseline in Urticaria Activity Score. Exploratory endpoints included CholU activity score over 7 days, urticaria control test, Physician Global Assessment, patient global assessment of severity (PGA-S), provocation tests, Dermatology Life Quality Index and CholU quality of life (CholU-QoL). Pharmacokinetic and pharmacodynamic parameters, and serum biomarkers were assessed, as well as safety and tolerability.

Results
Nineteen patients were randomized and included in the full analysis set; 18 completed treatment [mean (SD) age 29.5 (9.8) years; mean (SD) CholU duration 8.0 (6.3) years]. The primary and most of prespecified exploratory endpoints were not met; there were significant improvements in PGA-S for izuforant vs. placebo (P = 0.02), and nonsignificant improvements for other endpoints in quality of life and histamine skin prick test. All adverse events (AEs) experienced with izuforant were considered mild. The most frequently reported (&gt; 1 patient) were nausea (three patients) and upper abdominal pain (two patients), occurring more frequently with izuforant vs. placebo (one patient each). There were no treatment-related serious AEs and no patient receiving izuforant discontinued the study. Treatment with izuforant did not cause downregulation of H4R.

Conclusions
This is the first study to explore the role of H4R as a therapeutic target in urticaria. Targeting H4R with izuforant was well tolerated but did not demonstrate significant improvements vs. placebo in the primary endpoint and all but one prespecified exploratory endpoint in CholU.
A comprehensive list of genes required for the efficient conjugation of plasmid Rts1 was determined by systematic deletion analysis
Authors: Murata Takahiro , Gotoh Yasuhiro , Hayashi Tetsuya 
Published: February 2024

Abstract
While conjugation-related genes have been identified in many plasmids by genome sequencing, functional analyses have not yet been performed in most cases, and a full set of conjugation genes has been identified for only a few plasmids. Rts1, a prototype IncT plasmid, is a conjugative plasmid that was originally isolated from Proteus vulgaris. Here, we conducted a systematic deletion analysis of Rts1 to fully understand its conjugation system. Through this analysis along with complementation assays, we identified 32 genes that are required for the efficient conjugation of Rts1 from Escherichia coli to E. coli. In addition, the functions of the 28 genes were determined or predicted; 21 were involved in mating-pair formation, three were involved in DNA transfer and replication, including a relaxase gene belonging to the MOBH12 family, one was involved in coupling, and three were involved in transcriptional regulation. Among the functionally well-analysed conjugation systems, most of the 28 genes showed the highest similarity to those of the SXT element, which is an integrative conjugative element of Vibrio cholerae. The Rts1 conjugation gene set included all 23 genes required for the SXT system. Two groups of plasmids with conjugation systems nearly identical or very similar to that of Rts1 were also identified.
Digest: A model for speciation in island systems
Authors: Cornu Lydia 
Published: February 2024

Abstract
Ecological pulses, marked by rapid environmental shifts, shape species dynamics such as speciation. Princepe et al. 2024 explore how intermittent migration, seabed depth, and sea-level changes influence species richness in islands. Their model, revealing nuanced richness patterns and migration impacts, contributes to understanding island evolution and offers insights into real-world cases. Examining the Philippines Archipelago, known for rich biodiversity, parallels emerge, showcasing the complex interplay of isolation, land bridges, and sea-level shifts in shaping genetic diversity. Overall, the findings enhance our understanding of population evolution in dynamic island environments.
Do Parties Matter? Party Positions and European Voters’ Attitudes toward Economic and Political Globalization
Authors: Honeker Alex 
Published: February 2024

Abstract
To what extent do party positions influence voters’ attitudes toward the economic and political aspects of globalization? Initially an issue following a left-right dimension of conflict, globalization increasingly divides mainstream from nonmainstream parties. In this study, I argue that parties help citizens form opinions on globalization issues. I then use data on voters’ attitudes and party positions on globalization to test this supply-side theory of globalization attitudes on both economic and political dimensions. Holding demand-side factors such as economic self-interest and predispositions/values constant, I find that party positions strongly affect voters’ views on economic and political globalization, with the effect being similar to that of education. Moreover, I find that the effect of cues from left- and right-populist parties is much more negative than that of mainstream parties, replicating previous elite-level findings on the positioning of these party families. Finally, green party cues show conflicting results for the economic and political dimensions, with green cues affecting voters negatively on economic globalization but positively on political globalization. The findings in this study call for a deeper exploration of the supply-side determinants of globalization attitudes.
Association between Child Tax Credit advance payments and food insufficiency in households experiencing economic shocks
Authors: McCann Nicole C , Dean Lorraine T , Bovell-Ammon Allison , Ettinger de Cuba Stephanie , Green Tiffany , Shafer Paul R , Raifman Julia 
Published: February 2024

Abstract
The COVID-19 pandemic brought increases in economic shocks due to poor health and lost employment, which reduced economic well-being, especially in households with children. The American Rescue Plan Act of 2021 expanded Child Tax Credit (CTC) payments to include eligibility for the lowest income households, boosted benefit levels, and provided monthly advance payments to households with children. Using Census Household Pulse Survey respondent data from January 2021 to July 2022, we evaluated the association between these advance CTC monthly payments and food insufficiency among households with children experiencing health- or employment-related economic shocks (defined as missed work due to COVID-19/other illness or COVID-19–related employer closure/layoff/furlough). Using a triple difference design, we found that the advance CTC was associated with greater reductions in food insufficiency among households with children experiencing economic shocks both compared with households without children and with households with children not experiencing economic shocks. Permanently expanding the advance CTC could create resilience to economic shocks during disease outbreaks, climate disasters, and recessions.
Capacity configuration strategy for wind-photovoltaic-battery system based on optimized simulated annealing
Authors: Huang Haoru , Hu Zhijie , Xu Shuaishuai , Wang Xiaoling 
Published: February 2024

Abstract
Photovoltaic (PV) and wind power are very promising renewable energy sources. Wind-PV has good complementarity, and the battery can better smooth the power fluctuation of wind-PV, so the wind-PV-battery system has been widely used. The capacity configuration of the wind-PV-battery system is a complex issue because many factors affect it. Unlike other studies that focus on many meaningless parameters, the contribution of this paper is that we focus on three key elements, system reliability, cost, and wind-PV energy discard rate (EDR), which are the key factors affecting the capacity configuration of the system because system reliability and cost are factors that cannot be ignored during system operation. At the same time, the EDR is the government’s minimum requirement for system operation. Based on this, this paper establishes an optimization function to minimize the loss of power supply probability (LPSP), cost, and EDR, and then optimizes a simulated annealing (SA) algorithm to improve its optimization speed as well as accuracy, and finally verifies through simulation, that the optimized SA has better performance and can obtain a satisfactory reference configuration for wind-PV-battery capacity. Further, we have also analyzed the effectiveness obtained by applying retired batteries to the energy storage system. In our example, the cost of the system after using retired batteries is only about 61% of the cost of using new batteries, which suggests that utilizing retired batteries instead of new batteries has a better cost performance.
Racial (In)justice in Brazil: Reconstructing the Subaltern Memories of Poor and Black Women in the Brazilian Dictatorship
Authors: Pamplona Pablo , Besen Beatriz , de Wolff Kaya , Ansara Soraia , Galeão-Silva Luis 
Published: February 2024

ABSTRACT
The Brazilian military-corporate dictatorship faced the resistance and mobilization of several marginalized groups. In this article, we reconstruct the subaltern memories of Black and poor women from the outskirts of São Paulo who participated in Christian Base Communities and the Cost-of-Living Movement, and we show how their mobilization was supported by social movements across the country. Despite their dimension and impact, a report by the Brazilian National Truth Commission fails to recognize their role in the country’s democratic transition and the violence suffered by marginalized groups. These memories support a reflection on the myth of ‘racial democracy’ in Brazil as a general denial of racial violence throughout the country’s history, which leaves intact its structures of injustice. We argue that the reconstruction of subaltern memories can have a significant impact on transitional justice and recover their critical role in democracy.
When the Background Looms Large over the Foreground: Medical Professionals, Diplomats, and Co-Managing SARS-CoV-2
Authors: Kornprobst Markus , Strobl Stephanie 
Published: February 2024

Abstract
The Public Health Emergency of International Concern (PHEIC) is the highest alert that the World Health Organization (WHO) can issue. Even though the International Health Regulations (IHR 2005) prescribe tight deadlines and an expeditious decision-making process to determine such a PHEIC, it took many weeks for the alert to be declared to counter the spread of SARS-CoV-2 (coronavirus). What explains the delay? Drawing from recent advances in the literature on international orders, our argument zooms in on the troubled relations between medical professionals and diplomats. Practices enacting a hierarchical relationship between the medical and diplomatic communities of practice (background) undermined crucial parts of the decision-making mechanism laid out in the IHR, which puts medical professionals in a strong position (foreground). This study contributes to a better understanding of PHEICs, global health governance, and, beyond this, to how actors employing different lenses to make sense of the world fail or succeed to manage crises together. Our findings also have important policy implications for discussions about a Pandemic Treaty.
Effect of water sulfate and dietary bismuth subsalicylate on feed and water intake, ruminal hydrogen sulfide concentration, and trace-mineral status of growing beef heifers
Authors: Evans Mikaela G , Campbell John C , Ribeiro Gabriel O , Henry Darren H , Waldner Cheryl , Penner Gregory B 
Published: February 2024

Abstract
In the Northern Great Plains, cattle may be exposed to water with an elevated sulfate concentration resulting in ruminal hydrogen sulfide (H2S) production and risk of copper deficiency. There are currently few strategies available to help mitigate effects arising from high-sulfate water (HS). The objective of this study was to evaluate the effects of feeding a moderate-forage diet with or without bismuth subsalicylate (BSS; 0.0% vs. 0.4% DM basis) when provided water with a low- (LS; 346 ± 13) or HS (4,778 ± 263 mg/L) concentration on feed and water intake, ruminal H2S concentration, and liver and serum trace-mineral concentrations. Twenty-four Limousin × Simmental cross beef heifers (221 ± 41 kg) were stratified based on initial liver Cu into a completely randomized block design with a 2 × 2 factorial treatment arrangement. Feed and water intake (measured weekly), ruminal H2S concentration (measured on days 42 and 91), liver (measured on days −13 and 91), and serum trace-mineral concentrations (measured on days 1, 28, 56, and 91) were evaluated. Initial liver trace-mineral concentrations were used as a covariate in the statistical model. Water intake tended to be reduced with the inclusion of BSS (P = 0.095) but was not affected by water sulfate (P = 0.40). Water sulfate and BSS did not affect dry matter intake (DMI; P ≥ 0.89). Heifers consuming HS had a ruminal H2S concentration that was 1.58 mg/L more (P &lt; 0.001) than LS. The inclusion of BSS reduced (P = 0.035) ruminal H2S concentration by more than 44% (1.35 vs. 0.75 mg/L). Regardless of the water sulfate concentration, heifers fed BSS had lesser liver Cu concentration (average of 4.08 mg/kg) than heifers not provided BSS, and when not provided BSS, HS had lesser Cu than LS (42.2 vs. 58.3; sulfate × BSS, P = 0.019). The serum concentration of Cu did not differ over time for heifers not provided BSS; whereas, heifers provided BSS had lesser serum Cu concentration on day 91 than on days 28 and 55 (BSS × time, P &lt; 0.001). The liver concentration of selenium was reduced (P &lt; 0.001) with BSS inclusion but the selenium concentration in serum was not affected by sulfate, BSS, or time (P ≥ 0.16). BSS reduced ruminal H2S concentration, but depleted liver Cu and Se. Moreover, sulfate concentration in water did not appear to affect DMI, water intake, or growth, but increased ruminal H2S and reduced liver Cu concentration.
Male Lrp5A214V mice maintain high bone mass during dietary calcium restriction by altering the vitamin D endocrine system
Authors: Ozgurel Serra Ucer , Reyes Fernandez Perla C , Chanpaisaeng Krittikan , Fleet James C 
Published: February 2024

Abstract
Environmental factors and genetic variation individually impact bone. However, it is not clear how these factors interact to influence peak bone mass accrual. Here we tested whether genetically programmed high bone formation driven by missense mutations in the Lrp5 gene (Lrp5A214V) altered the sensitivity of mice to an environment of inadequate dietary calcium (Ca) intake. Weanling male Lrp5A214V mice and wildtype littermates (control) were fed AIN-93G diets with 0.125%, 0.25%, 0.5% (reference, basal), or 1% Ca from weaning until 12 weeks of age (ie, during bone growth). Urinary Ca, serum Ca, Ca regulatory hormones (PTH, 1,25 dihydroxyvitamin D3 (1,25(OH)2D3)), bone parameters (μCT, ash), and renal/intestinal gene expression were analyzed. As expected, low dietary Ca intake negatively impacted bones and Lrp5A214V mice had higher bone mass and ash content. Although bones of Lrp5A214V mice have more matrix to mineralize, their bones were not more susceptible to low dietary Ca intake. In control mice, low dietary Ca intake exerted expected effects on serum Ca (decreased), PTH (increased), and 1,25(OH)2D3 (increased) as well as their downstream actions (ie, reducing urinary Ca, increasing markers of intestinal Ca absorption). In contrast, Lrp5A214V mice had elevated serum Ca with a normal PTH response but a blunted 1,25(OH)2D3 response to low dietary Ca that was reflected in the renal 1,25(OH)2D3 producing/degrading enzymes, Cyp27b1 and Cyp24a1. Despite elevated serum Ca in Lrp5A214V mice, urinary Ca was not elevated. Despite an abnormal serum 1,25(OH)2D3 response to low dietary Ca, intestinal markers of Ca absorption (Trpv6, S100g mRNA) were elevated in Lrp5A214V mice and responded to low Ca intake. Collectively, our data indicate that the Lrp5A214V mutation induces changes in Ca homeostasis that permit mice to retain more Ca and support their high bone mass phenotype.
Electoral Campaigns as Dynamic Contests
Authors: Acharya Avidit , Grillo Edoardo , Sugaya Takuo , Turkel Eray 
Published: February 2024

Abstract
We develop a model of electoral campaigns in which two office-motivated candidates allocate their budgets over time to affect their odds of winning. We measure the candidates’ evolving odds of winning using a state variable that tends to decay over time, and we refer to it as the candidates’ “relative popularity.” In our baseline model, the equilibrium ratio of spending by each candidate equals the ratio of their initial budgets; spending is independent of past realizations of relative popularity; and there is a positive relationship between the strength of decay in the popularity process and the rate at which candidates increase their spending over time as election day approaches. We use this relationship to recover estimates of the perceived decay rate in popularity leads in U.S. subnational elections.
Challenging the existing order of knowledge sharing governance with digital sequence information on genetic resources
Authors: Lawson Charles , Humphries Fran , Rourke Michelle 
Published: February 2024

Abstract
The Conference of the Parties to the Convention on Biological Diversity (CBD) have begun work on establishing a distinct multilateral mechanism to access and share the benefits (ABS) from digital sequence information on genetic resources (DSI), with the expectation of new monetary benefits. Regulating DSI for benefit sharing is problematic because efficiently and effectively regulating information requires defining DSI and identifying a suitable material proxy for the information because it is itself intangible (probably a levy or tax to access or use a database of information). More problematic is finding a compromise to the competing information governance frameworks: a dominant international intellectual property order that favours the free exchange of resources and information (generally favoured by the technology rich North); the taking of nature by States and re-ordering of biological resources to deliver benefits (generally favoured by the technology poor South); and, the claims of Indigenous Peoples according to their emerging rights in international law.
Clinical Outcomes Associated with Amoxicillin Treatment for Acute Otitis Media in Children
Authors: Frost Holly M , Keith Amy , Fletcher Dana R , Sebastian Thresia , Dominguez Samuel R , Kurtz Melanie , Parker Sarah K , Wilson Michael L , Jenkins Timothy C 
Published: February 2024

Abstract

Background
Acute otitis media (AOM) is the most common reason children are prescribed antibiotics. Bacteria that produce beta-lactamase are an increasingly frequent cause of AOM and may be resistant to amoxicillin, the currently recommended treatment for AOM. We aimed to evaluate the clinical outcomes of children treated with amoxicillin for AOM and assessed whether outcomes vary by infecting pathogen or beta-lactamase production.

Methods
205 children 6-35 months old diagnosed with AOM and prescribed amoxicillin were included. Bacterial culture and qualitative multiplex real-time polymerase chain reaction were performed on nasopharyngeal swabs collected at enrollment. Parents completed surveys assessing symptoms, antibiotic adherence, and potential adverse events. The primary outcome was treatment failure with amoxicillin. Secondary outcomes included recurrence, symptom improvement, resolution, and adverse drug events (ADE).

Results
8 children (5.4%) experienced treatment failure and 14 (6.8%) had recurrence. By day 5, 152 (74.1%) children had symptom improvement and 97 (47.3%) had resolution. Parents reported ADE for 56 (27.3%) children. Among 149 children who did not take any amoxicillin before enrollment, 98 (65.8%) had one or more beta-lactamase-producing bacteria. Common bacterial otopathogens were Moraxella catarrhalis (79, 53.0%), Streptococcus pneumoniae (51, 34.2%), Haemophilus influenzae (30, 20.1%), and Staphylococcus aureus (21, 14.1%). Treatment failure did not differ between children that did (5, 5.1%) and did not (3, 5.9%) have beta-lactamase-producing otopathogens (p = .05).

Conclusions
Among children diagnosed with AOM treated with amoxicillin, treatment failure was uncommon and did not differ by pathogen or beta-lactamase production. These data support guidance recommending amoxicillin despite an increasing prevalence of beta-lactamase-producing bacteria.
Iatrogenic wandering spleen causing gastric outlet obstruction and perforation
Authors: Lieb K R , Beaulieu D , Dhir M 
Published: February 2024

Abstract
The phenomenon of a wandering spleen is rare with few published case reports. The cases published in the literature mainly result from acquired or congenital laxity of the spleen’s anchoring ligaments. Our case demonstrates an uncommon complication and possibly the first reported case of an iatrogenic wandering spleen. We present an interesting case of a 51-year-old female patient with congenital adrenal hyperplasia, fibromyalgia, and rheumatoid arthritis who underwent robotic-assisted left adrenalectomy for a 10-cm adrenal mass. Postoperatively, she developed uncontrolled pain and gastric distension due to spleen entrapment, leading to an open laparotomy and splenectomy with gastric perforation repair. She made an uneventful recovery. The rarity of iatrogenic wandering spleen as well as our patient’s complex medical history, including chronic steroid use, presented unique challenges in postoperative management. This case highlights the importance of thorough perioperative evaluation and careful surgical planning in patients with underlying conditions.