bluuebunny/crossref_metadata_2025_split huggingface dataset:
An endogenous cholinergic system controls electrical conduction in the heart
Authors: Xie Duanyang , Xiong Ke , Dong Nianguo , Wang Guanghua , Zou Qicheng , Shao Beihua , Chen Zhiwen , Wang Luxin , Kong Yu , Wang Xu , Su Xuling , Bai Wenli , Yang Jian , Liu Yi , Zhou Bin , Chen Yi-Han 
Published: October 2024

Abstract

Background and Aims
The cholinergic system is distributed in the nervous system, mediating electrical conduction through acetylcholine (ACh). This study aims to identify whether the heart possesses an intact endogenous cholinergic system and to explore its electrophysiological functions and relationship with arrhythmias in both humans and animals.

Methods
The components of the heart’s endogenous cholinergic system were identified by a combination of multiple molecular cell biology techniques. The relationship of this system with cardiac electrical conduction and arrhythmias was analysed through electrophysiological techniques.

Results
An intact cholinergic system including ACh, ACh transmitter vesicles, ACh transporters, ACh metabolic enzymes, and ACh receptors was identified in both human and mouse ventricular cardiomyocytes (VCs). The key components of the system significantly regulated the conductivity of electrical excitation among VCs. The influence of this system on electrical excitation conduction was further confirmed both in the mice with α4 or α7 nicotinic ACh receptors (nAChRs) knockouts and in the monolayers of human induced pluripotent stem cell-derived cardiomyocytes. Mechanistically, ACh induced an inward current through nAChRs to reduce the minimum threshold current required to generate an action potential in VCs, thereby enhancing the excitability that acts as a prerequisite for electrical conduction. Importantly, defects in this system were associated with fatal ventricular arrhythmias in both patients and mice.

Conclusions
This study identifies an integrated cholinergic system inherent to the heart, rather than external nerves that can effectively control cardiac electrical conduction. The discovery reveals arrhythmia mechanisms beyond classical theories and opens new directions for arrhythmia research.
Characterization of bacteriophage vB_AbaS_SA1 and its synergistic effects with antibiotics against clinical multidrug-resistant Acinetobacter baumannii isolates
Authors: Rastegar Sanaz , Sabouri Salehe , Tadjrobehkar Omid , Samareh Ali , Niaz Hira , Sanjari Nafise , Hosseini-Nave Hossein , Skurnik Mikael 
Published: October 2024

Abstract
Acinetobacter baumannii is a major cause of nosocomial infections globally. The increasing prevalence of multidrug-resistant (MDR) A. baumannii has become an important public health concern. To combat drug resistance, alternative methods such as phage therapy have been suggested. In total, 30 MDR A. baumannii strains were isolated from clinical specimens, and their antibiotic susceptibilities were determined. The Acinetobacter phage vB_AbaS_SA1, isolated from hospital sewage, was characterized. In addition to its plaque size, particle morphology, and host range, its genome sequence was determined and annotated. Finally, the antibacterial effects of phage alone, antibiotics alone, and phage/antibiotic combinations were assessed against the A. baumannii strains. Phage vB_AbaS_SA1 had siphovirus morphology, showed a latent period of 20 min, and a 250 PFU/cell (plaque forming unit/cell) burst size. When combined with antibiotics, vB_AbaS_SA1 (SA1) showed a significant phage-antibiotic synergy effect and reduced the overall effective concentration of antibiotics in time-kill assessments. The genome of SA1 is a linear double-stranded DNA of 50 108 bp in size with a guanine-cytosine (GC) content of 39.15%. Despite the potent antibacterial effect of SA1, it is necessary to perform additional research to completely elucidate the mechanisms of action and potential constraints associated with utilizing this bacteriophage.
Postpartum hepatitis flares in mothers with chronic hepatitis B infection
Authors: OuYang Shi , Geng Yawen , Qiu Gongqin , Deng Yueying , Deng Haitao , Pan Calvin Q 
Published: October 2024

Abstract
Postpartum elevation of alanine aminotransferase (ALT) in mothers with chronic hepatitis B (CHB) presents a significant clinical challenge. However, the existing literature demonstrates inconsistencies regarding its incidence and predictors in mothers infected with the hepatitis B virus (HBV). Recent advancements in antiviral prophylaxis against mother-to-child transmission of HBV and postpartum cessation of antiviral therapy further complicate this issue. Our literature review, spanning PubMed, and two Chinese-language databases (CNKI and Wanfang) from 1 January 2000 to 31 December 2023 aimed to consolidate and analyse available data on the frequency and severity of postpartum ALT flares, identify risk factors, and propose a management algorithm. Data from 23 eligible studies involving 8,077 pregnant women revealed an overall incidence of postpartum ALT elevation: 25.7% for mild cases, 4.4% for moderate cases, and 1.7% for severe cases. In the subgroup of mothers who were HBeAg-positive and on antiviral prophylaxis for preventing mother-to-child transmission, postpartum intermediate and severe ALT elevations were reported with pooled rates of 5.9% and 0.8%, respectively. Importantly, none resulted in mortality or necessitated liver transplantation. Identified risk factors for postpartum ALT flares in mothers with CHB included HBV DNA levels, ALT levels during pregnancy, postpartum cessation of antiviral treatment, and HBeAg status. By leveraging this evidence and recent data on predictors of intermediate or severe postpartum ALT flares, we propose a risk-stratified algorithm for managing postpartum ALT elevation and selecting therapy in mothers with CHB, tailoring different approaches for treatment-naive vs treatment-experienced populations. These recommendations aim to provide guidance for clinical decision-making and enhance patient outcomes.
Changes in Alcohol Intake by Educational Level Among Older Men and Women in Spain During the 21st Century
Authors: Donat Marta , Politi Julieta , Guerras Juan Miguel , Sordo Luis , Cea-Soriano Lucia , Pulido Jose , Ronda Elena , Regidor Enrique , Barrio Gregorio , Belza Maria José 
Published: October 2024

Abstract

Background and Objectives
Despite alcohol use being very common in older adults, studies are scarce and suggest alcohol use may be increasing. Furthermore, despite the known relationship between education and alcohol consumption, there is limited evidence of educational differences in older adults. Our objective was to describe trends in alcohol consumption in individuals aged ≥65 by sex and educational level in Spain.

Research Design and Methods
In total, 43,157 participants aged ≥65 years were drawn from Spain’s national health surveys between 2001 and 2020, representing the noninstitutionalized population. The outcomes were various measures of self-reported past-year alcohol intake. Age-standardized rates and negative binomial regression models were used to examine trends and differences in alcohol intake by educational level, sex, and period (2001–2009 vs 2011–2020).

Results
The average daily alcohol intake and prevalence of heavy average drinking (&gt;20/10 g/day) decreased over time, especially among men, whereas moderate average drinking remained unchanged or even increased. Alcohol intake increased with increasing educational levels. All drinking measures showed educational inequalities, and these were greater in women than men. The mean amount of drinking showed the greatest inequality, with adjusted prevalence ratio of 2.6 in women and 1.1 in men between university relative to primary education level.

Discussion and Implications
Alcohol intake in older adults decreased over time in Spain for heavy average drinking and average drinking amount, although not for moderate average drinking. Consumption remains highest among the highest educational levels, which may negatively affect health. Programs addressing alcohol consumption among older adults are needed to minimize alcohol-related harm.
Free Reflection Multiarrangements and Quasi-Invariants
Authors: Abe Takuro , Enomoto Naoya , Feigin Misha , Yoshinaga Masahiko 
Published: October 2024

Abstract
To a complex reflection arrangement with an invariant multiplicity function one can relate the space of logarithmic vector fields and the space of quasi-invariants, which are both modules over invariant polynomials. We establish a close relation between these modules. Berest–Chalykh freeness results for the module of quasi-invariants lead to new free complex reflection multiarrangements. Saito’s primitive derivative gives a linear map between certain spaces of quasi-invariants. We also establish a close relation between non-homogeneous quasi-invariants for root systems and logarithmic vector fields for the extended Catalan arrangements. As an application, we prove the freeness of Catalan arrangements corresponding to the non-reduced root system $BC_{N}$.
Infrastructures and International Relations: A Critical Reflection on Materials and Mobilities
Authors: Bakonyi Jutta , Darwich May 
Published: October 2024

Abstract
In a world of accelerated movements, this article examines how infrastructures matter in international relations. We first show that the International Relations (IR) discipline has relegated infrastructures to the background of their studies and treated them as passive tools despite their forcible role in the establishment of the modern state system. By adopting a sociological definition of “the international,” this article emphasizes the centrality of materials and mobilities in thinking about the international and calls for a novel infrastructural lens in the IR discipline. We argue that infrastructures provide crucial mechanisms for forging the distinctions between units that constitute the international as a separate realm. We outline how infrastructures continuously transform this realm through re-scaling and re-ordering spaces, polities, and people. In the meantime, infrastructures are at the heart of social processes, which generate knowledge practices that constitute the international. They inscribe themselves in discourses, produce meaning, and shape identities, and they are thus part of the ideational underpinning of the international. We conclude by advocating a shift in the analytical weight of materials in IR, premised on an interdisciplinary dialogue, and suggest a theoretical and methodological recalibration of the discipline’s treatment of infrastructures.
Online availability of antibiotics from within the UK: shifting patterns from 2016 to 2023
Authors: Boyd Sara Elizabeth , Zhu Nina , Whitney Laura , Surya Rohan , Holmes Alison Helen , Ahmad Raheelah 
Published: October 2024

Abstract

Background
We previously reported a cross-sectional analysis of online pharmacy practices and processes. Since then, the demand for and context of online healthcare has changed. However, the current state of access to and usage of antibiotics obtained online remains poorly understood.

Objectives
This study aimed to: (i) determine the legality of online pharmacies selling antibiotics in the UK; (ii) describe processes for obtaining antibiotics online; (iii) identify antimicrobial stewardship (AMS) and patient safety issues; and (iv) compare data with those obtained in 2016 to understand changes in context, and set priorities for targeted research in antibiotic access and usage.

Methods
Searches for ‘buy antibiotics online’ were conducted using ‘Google’ and ‘Yahoo’. The first 10 websites with unique URL addresses for each were reviewed. Analyses were conducted on evidence of pharmacy registration, prescription requirement, whether choice was ‘prescriber-driven’ or ‘consumer-driven’, and whether information was required (allergies, comorbidities, pregnancy) or given (adverse effects) prior to purchase.

Results
Twenty unique URL addresses were analysed. Those evidencing UK location (n = 20; 100%) required a prescription and were appropriately registered. For 11 (55%) online pharmacies, decisions were initially consumer-driven for antibiotic choice, but not for dose or duration; contrasting with 2016 when for most (n = 16; 80%), decisions were consumer-driven for antibiotic choice, dose and quantity.

Conclusions
Variation continues to exist in relation to antibiotic practices online. We make several key recommendations for lawmakers and stakeholders. Targeted research, improved public engagement, professional education and new best practice guidelines are urgently needed for online UK antibiotic suppliers.
Therapeutic drug monitoring (TDM) of β-lactam/β-lactamase inhibitor (BL/BLI) drug combinations: insights from a pharmacometric simulation study
Authors: O’Jeanson Amaury , Nielsen Elisabet I , Friberg Lena E 
Published: October 2024

Abstract

Background
The emergence of β-lactamase-producing bacteria has led to the use of β-lactam (BL) antibiotic and β-lactamase inhibitor (BLI) drug combinations. Despite therapeutic drug monitoring (TDM) being endorsed for BLs, the impact of TDM on BLIs remains unclear.

Objectives
Evaluate whether BLIs are available in effective exposures at the site of infection and assess if TDM of BLIs could be of interest.

Methods
Population pharmacokinetic models for 9 BL and BLI compounds were used to simulate drug concentrations at infection sites following EMA-approved dose regimens, considering plasma protein binding and tissue penetration. Predicted target site concentrations were used for probability of target attainment (PTA) analysis.

Results
Using EUCAST targets, satisfactory (≥90%) PTA was observed for BLs in patients with typical renal clearance (CrCL of 80 mL/min) across various sites of infection. However, results varied for BLIs. Avibactam achieved satisfactory PTA only in plasma, with reduced PTAs in abdomen (78%), lung (73%) and prostate (23%). Similarly, tazobactam resulted in unsatisfactory PTAs in intra-abdominal infections (79%), urinary tract infections (64%) and prostatitis (34%). Imipenem-relebactam and meropenem-vaborbactam achieved overall satisfactory PTAs, except in prostatitis and high-MIC infections for the latter combination.

Conclusions
This study highlights the risk of solely relying on TDM of BLs, as this can indicate acceptable exposures of the BL while the BLI concentration, and consequently the combination, can result in suboptimal performance in terms of bacterial killing. Thus, dose adjustments also based on plasma concentration measurements of BLIs, in particular for avibactam and tazobactam, can be valuable in clinical practice to obtain effective exposures at the target site.
The optimal dietary sodium and chloride level for broiler chicks fed a corn-soybean meal diet between 1 and 21 d of age
Authors: Zhang Weiyun , Hu Yun , Hu Yangyang , Xue Mengxiao , Yang Ke , Cui Xiaoyan , Li Tingting , Wang Shengchen , Zhang Liyang , Luo Xugang 
Published: October 2024

Abstract
The experiment was conducted to estimate the ideal dietary sodium (Na) and chloride (Cl) level for broilers during day 1 to 21 using a corn-soybean meal diet under a dietary Na:Cl ratio of 1:1. A total of 490 1-d-old Arbor Acres male broilers were randomly allotted by body weight to one of seven treatments in a completely randomized design. Each treatment consisted of seven replicate cages with 10 chicks per cage. Broilers were fed a Na and Cl-unsupplemented corn-soybean meal basal diet (control, containing 0.02% Na and 0.08% Cl) and the Na and Cl-supplemented basal diets containing 0.14%, 0.20%, 0.26%, 0.32%, 0.38%, and 0.44% Na and Cl levels, respectively for 21 d. The results indicated that average daily gain, average daily feed intake, blood partial pressure of CO2 and concentrations of HCO3−, total CO2, Na+, Cl−, base excess and anion gap, tibial ash, and ash Na contents of broilers were affected (P &lt; 0.001) by dietary Na and Cl level, and increased linearly (P &lt; 0.001) and quadratically (P &lt; 0.001) with increasing Na and Cl levels. Feed/gain ratio, mortality, blood K+ concentration, serum osmotic pressure and K+, glucose and uric acid concentrations as well as heart, liver, and kidney indices of broilers were affected (P &lt; 0.01) by dietary Na and Cl level, and decreased linearly (P &lt; 0.001) and quadratically (P &lt; 0.001) with increasing Na and Cl levels. The estimates of dietary optimal Na and Cl levels were 0.07% to 0.16% according to the best-fitted broken-line or asymptotic models (P &lt; 0.001) of the above sensitive indicators. Therefore, the optimal dietary Na and Cl level was suggested to be 0.16% to support all of the above Na and Cl metabolic requirements of broilers fed the corn-soybean meal diet during day 1 to 21, which is lower than the 0.20% recommendation by the Chinese Feeding Standard of Chicken (2004).
Coated oregano essential oil and cinnamaldehyde compounds supplementation improves growth performance, enhances immune responses, and inhibits cecal Escherichia coli proliferation of broilers
Authors: Liu Zhen , Mu Yingqi , Xing Tong , Zhao Liang , Li Jiaolong , Zhou Jianming , Zhang Lin , Gao Feng 
Published: October 2024

Abstract
Plant essential oils are unstable due to high volatility and easy oxidation, while microencapsulation provides a potentially effective strategy for increasing the stability of natural essential oils and preserving their function. This study examined the effects of feeding coated oregano essential oil and cinnamaldehyde (COEC) compounds on growth, immune organ development, intestinal morphology, mucosal immune function, and the cecal microbiota populations of broilers. Three hundred one-day-old male Arbor Acres broiler chicks were organized into 5 groups: 1) negative control fed basal diet alone (NC), 2) positive control receiving basal diet plus 50 mg/kg of chlortetracycline (CTC), 3) basal diet plus 150 mg/kg COEC (COEC150), 4) plus 300 mg/kg COEC (COEC300), and 5) plus 450 mg/kg COEC (COEC450). The supplement trial was continued for 42 d. The results showed that CTC, COEC300, and COEC450 treatments decreased the feed conversion ratio of broilers both in the starter and whole experiment phases, increased the height of jejunal villi at 21 d and the number of goblet cells and IgA-producing cells at 21 or 42 d compared with NC group (P &lt; 0.05). Members of the COEC300 treatment group had a higher thymus weight index and jejunum length index than birds of NC or CTC groups at 21 d (P &lt; 0.05). CTC and all COEC treatments decreased malondialdehyde content in jejunal mucosa at 42 d (P &lt; 0.05). The population of Escherichia coli (E. coli) in the cecal digesta at 21 d was lower in the CTC, COEC300, and COEC450 treatment groups compared with the NC group (P &lt; 0.05). In contrast to the CTC group, COEC supplementation dose-dependently accelerated body weight gain, improved jejunal morphology, decreased malondialdehyde content in jejunal mucosa, increased numbers of jejunal goblet cells and IgA-producing cells, and decreased the E. coli population in cecal digesta at 21 or 42 d (P &lt; 0.05). Thus, we concluded that feeding broiler chickens with 300 or 450 mg/kg in antibiotic-free diets can improve growth performance, enhance immune responses, and inhibit the proliferation of cecal pathogenic bacteria.
Bone mineral density over ten years after primary parathyroidectomy in multiple endocrine neoplasia type 1
Authors: Kuusela Emma , Kostiainen Iiro , Ritvonen Elina , Ryhänen Eeva M , Schalin-Jäntti Camilla 
Published: October 2024

Abstract
Primary hyperparathyroidism (PHPT) associated with multiple endocrine neoplasia type 1 (MEN1) impairs bone mineral density and causes osteoporosis already in young patients. We aimed to investigate bone mineral density (BMD) in a contemporary cohort of patients with MEN1-related PHPT after long-term follow-up and compare these results with that of healthy controls. Thirty-five patients with genetically confirmed MEN1 were diagnosed with MEN1 at mean age 28.7 ± 13.6 years. Thirty-two (91.4%) underwent primary parathyroidectomy at mean age 33.3 ± 13.7 years; 12 had undergone at least 2 surgeries with on average 7.3 ± 5.9 years between the operations. BMD was assessed by DXA at the end of mean follow-up, 13.2 years after the primary parathyroidectomy and compared with that of 35 age- and gender-matched controls. More than 10 years after the first parathyroidectomy, mean BMD in patients with MEN1 is in the normal range. However, it is still significantly lower compared with healthy controls.
An asymmetrical reinforcing spiral? Disentangling the longitudinal dynamics of media use and mainstream media trust
Authors: Tsfati Yariv , Vliegenthart Rens , Strömbäck Jesper , Lindgren Elina 
Published: October 2024

Abstract
While numerous studies have documented an association between mainstream media trust and mainstream media use, only little is known about potential causal mechanisms underlying the association. We theorize that selective exposure, social influence, and the reinforcing spirals model offer three possible mechanisms that may underlie the association. These possibilities were studied using random intercept cross-lagged panel models and latent curve models on a four-wave panel data set (n  = 3,540). For mainstream media, the results show an asymmetrical reinforcing spiral, in which the effect of mainstream media trust on use can be considered as one of yielding maintenance, while the impact of media use on mainstream media trust to a limited degree is in line with the notion of a spiral gradually (though inconsistently) increasing trust over time. We also find that use of right-wing alternative media consistently and sometimes robustly leads to decreasing mainstream media trust.
Postsurgical pyoderma gangrenosum after mastectomy with a familial component
Authors: Rogers Christine Courtney , Nepper Jordyn , Holzem Kassandra E , Cortina Chandler S 
Published: October 2024

Abstract
Postsurgical pyoderma gangrenosum (PSPG) is a rare, ulcerative skin condition that presents a diagnostic challenge due to its similar presentation to infectious etiologies in the postsurgical period—often leading to gratuitous and unnecessary surgery and antibiotic use. We report a 37-year-old female with breast cancer who received neoadjuvant chemotherapy and immunotherapy and underwent bilateral skin-sparing mastectomies who developed delayed bilateral mastectomy skin flap necrosis secondary to PSPG. This case had rare factors associated with the development of PSPG such as preoperative systemic therapy and a familial component. This case underscores the importance of early recognition of this rare disease and appropriate management of PSPG to prevent unnecessary interventions and ensure an optimal outcome.