bluuebunny/crossref_metadata_2025 huggingface dataset:
A new clinical index scale for measuring secondary alveolar bone grafting success based on canine eruption
Authors: Rivers Clare M , Grant Jaime , McIntyre Grant , Devlin Mark F D , Russell Craig J H , Gillgrass Toby
Published: December 2024

Objectives

To develop a reproducible, reliable clinical index of alveolar bone grafting (ABG) outcome based on the eruption position of the cleft canine tooth and determine the association between eruption position and radiographic outcome at 6 months post-grafting.

Methods

Children with complete, non-syndromic, unilateral/bilateral cleft lip and palate in the West of Scotland were identified. Post-ABG radiographic outcome (Kindelan index) and canine eruption position in children with a cleft of the alveolus who had undergone ABG were documented. A Kindelan score was assigned to the 6-month post-bone-graft radiograph. Following canine tooth eruption, four-point clinical index scale (CIS) scores were assigned to maxillary occlusal images taken prior to commencement of definitive orthodontics; 1—canine eruption in alveolar crest, 2—canine eruption buccal to alveolar crest, 3—canine eruption palatal to alveolar crest, and 4—canine impaction. Intra and inter-rater reliability was assessed using Cohen and Fleiss kappa’s, respectively. Duration of orthodontics treatment, number of orthodontic clinic visits, and clinical management of the cleft site space were noted.

Results

Eighty-three patients representing 98 bone graft sites were identified. CIS scoring intra- and inter-rater reliability was 0.69–0.99 and 0.63–0.75, respectively. CIS score was associated with reduced visits (P = .015), months in orthodontics (P = .009), and likelihood of space closure (P = .006).

Limitations

This is a retrospective study with small numbers but is comparative to other similar studies in the literature.

Conclusions

The CIS presented appears to be a reliable index of ABG outcome. It also demonstrates an association with the burden of orthodontic care post-cleft alveolar bone graft.
Adverse pregnancy outcomes, familial predisposition, and cardiovascular risk: a Swedish nationwide study
Authors: Mantel Ängla , Wollmann Charlotte Lindblad , Faxén Jonas , Sandström Anna , Mühlrad Hanna , Stephansson Olof
Published: December 2024

Background and Aims

Adverse pregnancy outcomes (APOs) are recognized as significant female-specific risk factors for cardiovascular disease (CVD). A potential shared familial susceptibility between APOs and CVD has been proposed, but not thoroughly explored. This study employs a quasi-experimental family comparison design to investigate shared familial predisposition between APOs and CVD, by assessing risk of CVD in APO-exposed women and their APO-free sisters.

Methods

Nationwide population-based cohort study encompassing primiparous women, without prior CVD, with registered singleton births in the Swedish Medical Birth Register between 1992 and 2019, grouped into: women with ≥1 APO (165 628), APO-free sisters (60 769), and unrelated APO-free comparator women (992 108). All study participants were followed longitudinally, through linkage with national health registers, from delivery until 2021, for primary endpoint major adverse cardiac events, and its individual components: ischaemic heart disease, heart failure, and cerebrovascular events.

Results

Over a median follow-up of 14 years, APO-exposed women exhibited increased rates of CVDs compared with APO-free comparators. Adverse pregnancy outcome–free sisters exhibited elevated adjusted hazard ratios (aHRs) of major adverse cardiac event {aHR 1.39 [95% confidence interval (CI) 1.13–1.71]}, heart failure [aHR 1.65 (95% CI 1.14–2.39)], and cerebrovascular events [aHR 1.37 (1.04–1.72)] compared with the APO-free comparators, while no significant increase in ischaemic heart disease was observed. Within-family analysis revealed lower CVD rates in APO-free sisters compared with their APO-exposed counterparts, except for no significant difference in cerebrovascular events.

Conclusions

Sisters of women with APOs face a moderately increased risk of CVD, suggesting a genetic and/or environmental influence on the association between APOs and CVDs. These findings underscore the need for evaluating the effectiveness of targeted preventive measures in women with APOs and their sisters.
Systematic Coronary Risk Evaluation 2 for Older Persons: 10 years risk validation, clinical utility, and potential improvement
Authors: Belahnech Yassin , Ródenas-Alesina Eduard , Muñoz Miguel Ángel , Verdu-Rotellar Jose María , Sao-Avilés Augusto , Urio-Garmendia Garazi , Osorio Dimelza , Salas Karla , Pantoja Efrain , Ribera Aida , Ferreira-González Ignacio
Published: December 2024

Aims

European Systematic Coronary Risk Assessment 2 for Older Persons (SCORE2-OP) model has shown modest performance when externally validated in selected cohorts. We aim to investigate its predictive performance and clinical utility for 10-year cardiovascular (CV) risk in an unbiased and representative cohort of older people of a low CV risk country. Furthermore, we explore whether other clinical or echocardiographic features could improve its performance.

Methods and results

A cohort of randomly selected individuals ≥65 years from a primary care population of Barcelona without established CV disease included 791 patients (63.1% female, median age 76 years, median follow-up 11.8 years). The model’s performance yielded a Harrell’s C-statistic of 0.706 (95% confidence interval [CI] 0.659–0.753) for the primary endpoint (myocardial infarction, stroke, and CV mortality) and 0.692 (95% CI 0.649–0.734) for the secondary endpoint (primary endpoint plus heart failure hospitalization), with better discrimination in females. SCORE2-OP underestimated the risk of primary endpoint in women [expected/observed (E/O) = 0.77], slightly overestimated in men (E/O = 1.06), and systematically underestimated the risk of the secondary endpoint (E/O = 0.52). Decision curve analysis showed net clinical benefit across a 7.5–30% risk range for primary endpoint. Valvular calcification was the only variable that significantly improved 10-year SCORE2-OP risk performance for both primary and secondary endpoints, with a change in Harrell’s C of 0.028 (P = 0.017).

Conclusion

In a low CV risk country, SCORE2-OP showed notable discrimination and excellent calibration to predict 10-year CV risk, with better performance in females. Incorporating valvular calcification in a future revised score may enhance accuracy and reduce unnecessary treatments.
Metabolic dysfunction–associated steatotic liver disease, hypertriglyceridaemia, and cardiovascular risk
Authors: Gurevitz Chen , Rosenson Robert S
Published: December 2024

Metabolic dysfunction–associated steatotic liver disease (MASLD) encompasses a spectrum of liver conditions ranging from simple steatosis to the more severe metabolic dysfunction–associated steatohepatitis. Metabolic dysfunction–associated steatotic liver disease is strongly linked to insulin resistance disorders, with a high prevalence among patients with type 2 diabetes. Long-term complications include liver cirrhosis, liver cancer, and cardiovascular disease. This article elucidates the complex interplay between hypertriglyceridaemia, obesity, insulin resistance, and MASLD and provides an exploration of various aetiologies, including genetic predispositions and secondary factors such as diabetes, medication use, and alcohol consumption. While MASLD treatment remains an unmet need, multiple pharmacological therapies are targeting hypertriglyceridaemia and MASLD, including statins, peroxisome proliferator–activated receptor agonists, biguanides, incretins, and emerging therapies including angiopoietin-like 3 and apolipoprotein C-III inhibitors, fibroblast growth factor 21 analogues, and thyroid hormone receptor agonists. By examining these interconnected facets, this review offers insights into potential therapeutic strategies for MASLD and associated comorbidities.
Air pollution, genetic susceptibility, and the risk of ventricular arrhythmias: a prospective cohort study in the UK Biobank
Authors: Cheng Yun-Jiu , Zhu Chen , Deng Hai , Wu Yang , Wei Hui-Qiang , Lin Wei-Dong , Kaisaier Wulamiding , Li Runkai , Chen Yili , Dong Yugang , Fang Xian-Hong , Liao Yi-Jian , Wu Shu-Lin , Liao Hong-Tao , Xue Yu-Mei , Wu Zexuan
Published: December 2024

Aims

Both genetic and environmental factors contribute to the development of ventricular arrhythmias (VAs). However, the extent to which genetic susceptibility modifies the effects of air pollutants on the risk of VAs remains poorly understood.

Methods and results

This study included 491 305 participants without VAs at baseline from UK Biobank. Exposure to ambient air pollutants, including particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOX), was estimated through land use regression modelling. The associations between air pollutants and the incidence of VAs were then investigated using a Cox proportional hazards model adjusted for covariates. Additionally, we established a polygenic risk score for VAs and assessed the joint effect of genetic susceptibility and air pollution on incident VAs. During a median follow-up of 14.3 years, 4333 participants were diagnosed with VAs. Increased long-term exposure to PM2.5, PM10, NO2, and NOx was significantly associated with higher risks of VAs, with hazard ratios (HRs) per quintile increase of 1.07 (95% confidence interval, 95% CI: 1.03–1.11), 1.07 (1.03–1.11), 1.10 (1.06–1.14), and 1.08 (1.05–1.12) for each pollutant, respectively. Notably, there were significant additive interactions between air pollutants and genetic risk. Participants with both high genetic risk and high exposure to air pollution exhibited the greatest risk of VAs, with the highest HRs observed for PM2.5 (HR, 4.51; 95% CI, 3.66–5.56), PM10 (HR, 4.28; 95% CI, 3.52–5.22), NO2 (HR, 4.90; 95% CI, 3.97–6.03), and NOx (HR, 4.56; 95% CI, 3.72–5.60), respectively.

Conclusion

Long-term exposure to air pollution is associated with an increased risk of VAs, especially in individuals with a high genetic risk.
Increased Anion Exchanger-1 (Band 3) on the Red Blood Cell Membrane Accelerates Scavenging of Nitric Oxide Metabolites and Predisposes Hypertension Risks
Authors: Chen Li-Yang , Chen Pin-Lung , Jiang Si-Tse , Lee Hui-Lin , Liu Yen-Yu , Chueh Alysa , Lin Jing-Heng , Chen Caleb G , Hung Chung-Lieh , Hsu Kate
Published: December 2024

The erythrocyte membrane is highly specialized with ∼1 million anion exchanger-1 (AE1) per cell for rapid membrane permeation of HCO3−(aq), as most blood CO2(g) is carried in this hydrated anionic form. People with the GP.Mur blood type have more AE1 on their erythrocyte membrane, and they excrete CO2(g) more efficiently. Unexpectedly, GP.Mur/increased AE1 is also associated with higher blood pressure (BP). To solve this, we knocked the human GYP.Mur gene into C57BL/6J mice at 3′-UTR of GYPA to generate GPMur knock-in (KI) mice. KI of human GYP.Mur increased murine AE1 expression on the red blood cells (RBC). GPMur KI mice were naturally hypertensive, with normal kidney functions and lipid profiles. Blood NO3− [the stable nitric oxide (NO) reservoir] was significantly lower in the GPMur mice. GPMur KI also accelerated AE1-mediated NO2− influx into the RBCs and intraerythrocytic NO2−/NO processing. From tests with different categories of antihypertensives, hypertension in GPMur mice responded best to direct arterial vasodilator hydralazine, suggesting that vasodilator deficiency is the leading cause of “GPMur/AE1-triggered hypertension.” In conclusion, we showed that GPMur/increased AE1 predisposed hypertension risks. Mechanistically, higher AE1 expression increased RBC membrane permeability for NO2− and consequently accelerated erythroid NO2−/NO metabolism; this is associated with lower NO bioavailability and higher BP. As hypertension affects a quarter of the world population and GP.Mur is a common Southeast Asian (SEA) blood type, this work may serve as a primer for “GPMur (biomarker)-based” therapeutic development for hypertension.
Transcriptome and Evolutionary Analysis of Pseudotrichomonas keilini, a Free-Living Anaerobic Eukaryote
Authors: Abu-Elmakarem Hend , Taerum Stephen J , Petitjean Celine , Kotyk Michael , Kay Christopher , Čepička Ivan , Bass David , Gile Gillian H , Williams Tom A
Published: December 2024

The early evolution of eukaryotes and their adaptations to low-oxygen environments are fascinating open questions in biology. Genome-scale data from novel eukaryotes, and particularly from free-living lineages, are the key to answering these questions. The Parabasalia are a major group of anaerobic eukaryotes that form the most speciose lineage of Metamonada. The most well-studied are parasitic parabasalids, including Trichomonas vaginalis and Tritrichomonas foetus, but very little genome-scale data are available for free-living members of the group. Here, we sequenced the transcriptome of Pseudotrichomonas keilini, a free-living parabasalian. Comparative genomic analysis indicated that P. keilini possesses a metabolism and gene complement that are in many respects similar to its parasitic relative T. vaginalis and that in the time since their most recent common ancestor, it is the T. vaginalis lineage that has experienced more genomic change, likely due to the transition to a parasitic lifestyle. Features shared between P. keilini and T. vaginalis include a hydrogenosome (anaerobic mitochondrial homolog) that we predict to function much as in T. vaginalis and a complete glycolytic pathway that is likely to represent one of the primary means by which P. keilini obtains ATP. Phylogenomic analysis indicates that P. keilini branches within a clade of endobiotic parabasalids, consistent with the hypothesis that different parabasalid lineages evolved toward parasitic or free-living lifestyles from an endobiotic, anaerobic, or microaerophilic common ancestor.
Family Care Partners and Paid Caregivers: National Estimates of Role-Sharing in Home Care
Authors: Fabius Chanee D , Gallo Joseph J , Burgdorf JuliaG , Samus Quincy M , Skehan Maureen , Stockwell Ian , Wolff Jennifer L
Published: December 2024

Background and Objectives

We describe “role-sharing” in home care, defined as family care partners and paid caregivers assisting with the same task(s).

Research Design and Methods

We studied 440 participants in the 2015 National Health and Aging Trends Study receiving paid help with self-care, mobility, or medical care. We describe patterns in receiving paid help only, help from care partners only, and role-sharing. We examine whether sole reliance on paid help or role-sharing differs by Medicaid-enrollment and dementia status.

Results

Half (52.9%) of care networks involved role-sharing. Care networks involving role-sharing more often occurred among older adults with dementia (48.7% vs 25.6%, p < .001) and less often for those who were Medicaid-enrolled (32.1% vs 49.4%, p < .01). Those living with dementia more often experienced role-sharing in eating (odds ratio [OR] 3.9 [95% confidence interval {CI} 1.20, 8.50]), bathing (OR 2.7, [95% CI 1.50, 4.96]), dressing (OR 2.1 [95% CI 1.14, 3.86]), toileting (OR 2.9 [95% CI 1.23, 6.74]), and indoor mobility (OR 2.8 [95% CI 1.42, 5.56]), and less often received help solely from paid helpers with medication administration (OR 0.24, [95% CI .12, .46]). Medicaid-enrollees more often received paid help only in dressing (OR 2.0 [95% CI 1.12, 3.74]), outdoor (OR 2.4 [95% CI 1.28, 4.36]), and indoor mobility (OR 4.3 [95% CI 2.41, 7.62]), and with doctor visits (OR 2.8 [95% CI 1.29, 5.94]).

Discussion and Implications

Role-sharing is common, especially among older adults living with dementia who are not Medicaid-enrolled. Strategies supporting information sharing and collaboration in home-based care merit investigation.
Copyright and Research in Latin America: Law, Courts, and Perceptions
Authors: Valente Mariana G , Lana Alice P , Houang André P
Published: December 2024

Research on the intersection of copyright law, research activities, and innovation in Latin America reveals significant deficiencies in the legal framework and public discourse surrounding copyright limitations and exceptions (L&Es) for research purposes. The problem is more visible with modern data assembling and analyzing techniques, such as through artificial intelligence (AI) systems. This study highlights the scarcity of explicit provisions for research-related exceptions in the region by examining copyright legislation, case law, and stakeholder perspectives in six Latin American countries. Despite indications that judicial interpretation is expanding the scope of L&Es, particularly in Brazil, awareness of legal nuances remains low among researchers and broader stakeholder communities, hindering meaningful public discourse on the need for copyright reform. Our findings underscore the imperative to enhance awareness, foster community engagement, and promote public dialogue to advocate for legal reforms that balance copyright protection and research freedoms. Moreover, the lack of robust L&Es for research in the Global South exacerbates disparities with the Global North and impedes progress in fields reliant on copyrighted materials, such as AI research.
Navigating the Reformation in Suffolk: the painters’ perspectives
Authors: Tittler Robert
Published: December 2024

Scholarship on the impact of the English Reformation on the visual culture of the era has ignored the role of the painters who helped produce it. Yet it was the painters with their brushes no less than the preachers with their sermons who articulated the doctrinal and social developments of the era. Taking the example of Suffolk, this study examines the implications of the Reformation era for the painters’ occupation – including arms painters, glass painters, decorative painters and figurative painters – in provincial England. It supports its discussion with a biographical directory of Suffolk painters in the era c.1490–1640.
Reconstructing half a century of coregonine recruitment reveals species-specific dynamics and synchrony across the Laurentian Great Lakes
Authors: Brown Taylor A , Rudstam Lars G , Sethi Suresh A , Ripple Paul , Smith Jason B , Treska Ted J , Hessell Christopher , Olsen Erik , He Ji X , Jonas Jory L , Rook Benjamin J , Blankenheim Joshua E , Beech Sarah J H , Brown Erin , Berglund Eric K , Cook H Andrew , Dunlop Erin S , James Stephen , Pothoven Steven A , Amidon Zachary J , Sweka John A , Carl Dray D , Hansen Scott P , Bunnell David B , Weidel Brian C , Honsey Andrew E
Published: December 2024

Understanding how multiple species and populations vary in their recruitment dynamics can elucidate the processes driving recruitment across space and time. Lake Whitefish (Coregonus clupeaformis) and Cisco (C. artedi) are socioecologically important fishes across their range; however, many Laurentian Great Lakes populations have experienced declining, poor, or sporadic recruitment in recent decades. We integrated catch and age data from 38 long-term surveys across each of the Great Lakes and Lake Simcoe, resulting in a combined time series spanning 1960–2019. We estimated Lake Whitefish and Cisco year-class strength (YCS) in each lake using longitudinal mixed-effects regressions of relative cohort abundance. We subsequently quantified interspecific, spatial, and temporal synchrony in YCS using correlation and dynamic factor analyses. Lake Whitefish YCS was positively spatially synchronous on average, and YCS in all six lakes was elevated during the 1980s–1990s. In contrast, Cisco YCS was sporadic, not spatially synchronous, and highly variable around long-term, lake-specific means. YCS was not synchronous between species in any lake. Collectively, our analyses demonstrate that these species exhibit differential recruitment dynamics that may be regulated by species-specific factors. Results from this study can be leveraged in future research on the causes and consequences of cross-species, cross-basin recruitment variability.
Comparing unilateral and bilateral cerebral perfusion during total arch replacement for acute type A aortic dissection
Authors: Ji Yumeng , Qiu Juntao , Zhang Kai , Qin Huiyuan , Song Jian , Zhou Chenyu , Gao Shiqi , Hou Bin , Cao Fangfang , Wang Ji , Yu Cuntao , Gao Wei
Published: December 2024

OBJECTIVES

To assess the effects of unilateral versus bilateral antegrade cerebral perfusion (u-ACP vs. b-ACP) on postoperative complications and mid-term follow-up results in Asian patients with acute type A aortic dissection (ATAAD) undergoing total arch replacement (TAR) + the frozen elephant trunk (FET).

METHODS

Clinical baseline data and postoperative complications of 702 ATAAD patients undergoing TAR + FET at China Cardiovascular Centre Fuwai Hospital between January 2019 and December 2022 were collected. Patients were categorized into two groups based on ACP: unilateral (n = 402) and bilateral (n = 300). Propensity scores were matched for 217 pairs of patients. Mid-term and perioperative surgical complications were analysed, and baseline characteristics between the two groups were assessed.

RESULTS

The matched cohort revealed comparable 30-day mortality rates between u-ACP and b-ACP: 4.15% and 3.23%, respectively (P = 0.61). Rates of postoperative permanent neurologic dysfunction (PND) were similar across groups (2.76% for u-ACP and 3.23% for b-ACP, P = 0.76). However, u-ACP exhibited a higher incidence of postoperative transient neurologic deficit (TND) at 14.29% compared to 6.91% with b-ACP (P = 0.01). Logistic regression models identified u-ACP and cardiopulmonary bypass (CPB) time as independent risk factors for TND. Mid-term survival rates were comparable between the two groups (5-year survival: 90.29% vs. 93.67%, P = 0.133).

CONCLUSIONS

Both u-ACP and b-ACP are effective brain protection techniques for ATAAD patients undergoing TAR. The use of b-ACP significantly reduces the incidence of TND.
Nearly minimax optimal Wasserstein conditional independence testing
Authors: Neykov Matey , Wasserman Larry , Kim Ilmun , Balakrishnan Sivaraman
Published: December 2024

This paper is concerned with minimax conditional independence testing. In contrast to some previous works on the topic, which use the total variation distance to separate the null from the alternative, here we use the Wasserstein distance. In addition, we impose Wasserstein smoothness conditions that on bounded domains are weaker than the corresponding total variation smoothness imposed, for instance, by Neykov et al. (2021, Ann. Statist., 49, 2151–2177). This added flexibility expands the distributions that are allowed under the null and the alternative to include distributions that may contain point masses for instance. We characterize the optimal rate of the critical radius of testing up to logarithmic factors. Our test statistic that nearly achieves the optimal critical radius is novel, and can be thought of as a weighted multi-resolution version of the $U$-statistic studied by Neykov et al. (2021, Ann. Statist., 49, 2151–2177).
Differentially private low-dimensional synthetic data from high-dimensional datasets
Authors: He Yiyun , Strohmer Thomas , Vershynin Roman , Zhu Yizhe
Published: December 2024

Differentially private synthetic data provide a powerful mechanism to enable data analysis while protecting sensitive information about individuals. However, when the data lie in a high-dimensional space, the accuracy of the synthetic data suffers from the curse of dimensionality. In this paper, we propose a differentially private algorithm to generate low-dimensional synthetic data efficiently from a high-dimensional dataset with a utility guarantee with respect to the Wasserstein distance. A key step of our algorithm is a private principal component analysis (PCA) procedure with a near-optimal accuracy bound that circumvents the curse of dimensionality. Unlike the standard perturbation analysis, our analysis of private PCA works without assuming the spectral gap for the covariance matrix.
Getting a Foot in the Door: Lessons for the UK from Australian and New Zealand Approaches to Trade Union Right of Entry
Authors: McFarlane Katherine
Published: December 2024

British trade unions currently have limited statutory scope to enter workplaces and access the workers therein. The importance of facilitating union access has been repeatedly recognised in Australia and New Zealand, where substantive rights of entry are enshrined in legislation. The British Labour Party has recognised the importance of allowing unions to enter workplaces and committed to introducing statutory entry rights as an election promise. This article examines whether the Australian or New Zealand legislative schemes could be used as a blueprint for drafting equivalent British legislation. A comparison of the respective regimes reveals that the Australian laws are more regulated, restrictive and complex than the New Zealand provisions. The article ultimately advocates for the New Zealand legislation to be used as a model framework if analogous rights are enacted in Britain, but acknowledges that some features of the Australian regime might be attractive to employers and stakeholders who are cautious about expanding union rights. The Australian and New Zealand provisions have been subject to frequent reform since their enactment, mirroring the attitudes of successive governments towards trade unions. Any equivalent rights introduced in Britain will likely follow a similar trajectory over time.
Landscape of Bacterial Enteric Disease and Traveler´s Diarrhea in South America
Authors: Gaspar Carlos , Rios Paul , Moeller Tyler D
Published: December 2024

Diarrheal disease is a global public health threat. Cases of enteric disease caused by bacterial enteropathogens result in a significant health burden and can lead to antimicrobial resistance patterns that increase and evolve over time and geography, posing serious health challenges for local populations as well as civilian travelers and military personnel deployed to endemic regions. This review describes the prevalence of the most common bacterial agents of diarrheal disease in South America, as well as the distribution patterns of antibiotic resistance and predominant strains that are present in the region. Furthermore, the development of relevant prevention and treatment strategies are described, and United States Naval Medical Research Unit SOUTH disease surveillance and enteric disease research efforts in this regional context are highlighted.
Metagenomics reveals the genetic diversity between sublineages of UCYN-A and their algal host plastids
Authors: Kantor Ella Joy H , Robicheau Brent M , Tolman Jennifer , Archibald John M , LaRoche Julie
Published: December 2024

UCYN-A (or Cand. Atelocyanobacterium thalassa) has been recognized as a globally distributed, early stage, nitrogen-fixing organelle (the “nitroplast”) of cyanobacterial origin present in the haptophyte alga Braarudosphaera bigelowii. Although the nitroplast was recognized as UCYN-A2, not all sublineages of UCYN-A have been confirmed as nitroplasts, and full genomes are still lacking for several known sublineages. We investigated the differences between UCYN-A sublineages by sequencing and assembly of metagenomic sequences acquired from cultured biomass from NW Atlantic seawater, which yielded near-complete Metagenome Assembled Genomes (MAGs) corresponding to UCYN-A1, -A4, and the plastid of the UCYN-A4-associated B. bigelowii. Weekly time-series data paired with the recurrence of specific microbes in cultures used for metagenomics gave further insight into the microbial community associated with the algal/UCYN-A complex. The UCYN-A1 MAG was found to have 99% average nucleotide identity (ANI) to the Pacific-derived reference genome despite its Atlantic Ocean origin. Comparison of the UCYN-A4 MAG (the initial genome sequenced from this sublineage) to other genomes showed that UCYN-A4 is sufficiently genetically distinct from both UCYN-A1 and UCYN-A2 (ANI of ~83% and ~85%, respectively) to be considered its own sublineage, but more similar to UCYN-A2 than -A1, supporting its possible classification as a nitroplast. The B. bigelowii plastid sequence was compared with published plastid sequences (sharing 78% ANI with Chrysochromulina parva) adding to our understanding of genomic variation across Haptophyta organelles and emphasizing the need for further full genomic sequencing of B. bigelowii genotypes and their organelles.
Phenotypic antibiotic resistance of Mycoplasma genitalium and its variation between different macrolide resistance-associated mutations
Authors: Doelman T A , Adriaens N , Westerhuis B M , Bruisten S M , Vergunst C E , Bouwman F M , van Dam A P
Published: December 2024

Objectives

Mycoplasma genitalium, a sexually transmitted bacterium, faces increasing antibiotic resistance, particularly to azithromycin. However, presence of macrolide resistance-associated mutations (MRAMs) does not evidently implicate azithromycin treatment failure. This study aimed to establish an in vitro co-culture system of M. genitalium isolates and perform phenotypic susceptibility testing for different antibiotics, focusing on azithromycin to evaluate genotypic and phenotypic resistance across MRAMs.

Methods

Urine specimens testing positive for M. genitalium via nucleic acid amplification were co-cultured with Vero cells. Phenotypic susceptibility testing was performed for eight antibiotics. Growth inhibition and MIC of M. genitalium by azithromycin were compared across different MRAMs.

Results

M. genitalium was cultured from 20/40 (50.0%) positive urine samples, with phenotypic susceptibility tested in a subset. MICs ranged as follows: azithromycin (0.008–>32 mg/L), levofloxacin (1–4 mg/L), moxifloxacin (<0.25–1 mg/L), sitafloxacin (<0.032–0.25 mg/L), minocycline (<0.25–1 mg/L), doxycycline (<0.125–2 mg/L), spectinomycin (<2.5–>25 mg/L) and lefamulin (<0.004–0.063 mg/L). Isolates with A2058T demonstrated 24-, 7-, 15- and 12-fold increases in growth inhibition compared with A2058G at azithromycin concentrations of 4, 8, 16 and 32 mg/L, respectively (P < 0.01). MRAMs ranked from low to high impact on MIC range were as follows: wildtype (0.008–0.016), A2058T (8–32), A2059G (≥32) and A2058G (>32).

Conclusions

This study revealed that M. genitalium isolates vary in azithromycin-induced growth inhibition across MRAMs, potentially explaining differences in clinical treatment efficacy. Phenotypic susceptibility testing for other antibiotics demonstrated relatively low MICs. Future studies should incorporate clinical treatment efficacy and symptom severity to optimize treatment for M. genitalium.
Evaluating the effects of ivacaftor exposure on Staphylococcus aureus small colony variant development and antibiotic tolerance
Authors: Bollar Gretchen E , Shaffer Kendall M , Keith Johnathan D , Oden Ashley M , Dowell Alexander E , Ryan Kevin J , Acosta Edward P , Guimbellot Jennifer S , Kiedrowski Megan R , Birket Susan E
Published: December 2024

Background

Ivacaftor exhibits anti-staphylococcal properties but does not clear Staphylococcus aureus from the lungs of people with cystic fibrosis (pwCF). We assessed whether exposure to therapeutic concentrations of ivacaftor could allow S. aureus to form small colony variants (SCVs), a phenotype commonly associated with bacterial persistence.

Methods

Humanized G551D-CFTR (hG551D) rats were treated with ivacaftor for 7 days. Concentrations in the plasma, epithelial lining fluid and lung tissue lysate were measured using LC-MS/MS. Survival of S. aureus during ivacaftor treatment was assessed in an hG551D rat model of lung infection. S. aureus adaptation to therapeutic concentrations of ivacaftor was investigated in vitro by serial passage in the presence of 10 µM ivacaftor. Bacterial survival in the presence of antimicrobials was evaluated using growth curves and density assays.

Results

Ivacaftor plasma concentrations of treated hG551D rats reached 3.488 ± 1.118 µM, with more variable concentrations in the epithelial lining fluid and lung tissue lysate. During S. aureus infection, ivacaftor-treated hG551D rats returned similar numbers of bacteria from the lung, compared with vehicle-treated controls. Exposure of S. aureus to ivacaftor in vitro led to the formation of ivacaftor-tolerant SCVs with an unstable phenotype and increased antibiotic tolerance.

Conclusions

Treatment with ivacaftor did not alter S. aureus burden in the cystic fibrosis rat and led to the formation of tolerant SCVs in vitro, suggesting that development of an SCV phenotype may allow S. aureus to persist in the cystic fibrosis lung during ivacaftor therapy.
Paediatricians’ knowledge, perceptions, preparedness and involvement towards paediatric antimicrobial stewardship in Pakistan: findings and the implications
Authors: Mustafa Zia Ul , Khan Amer Hayat , Salman Muhammad , Harun Sabariah Noor , Meyer Johanna C , Godman Brian
Published: December 2024

Introduction

Antibiotics are frequently prescribed for neonates and children. However, this can be excessive with inappropriate prescribing leading to increased antimicrobial resistance (AMR). Paediatricians are key initiators of antibiotics. Consequently, their awareness, perceptions, readiness and potential barriers towards hospital-based antimicrobial stewardship programmes are of considerable importance, especially in Pakistan with high rates of AMR.

Materials and methods

A web-based cross-sectional survey among paediatricians from June to August 2023 using a validated questionnaire. Paediatricians from all four Provinces and the capital territory of Pakistan were invited from randomly selected public and private sector hospitals.

Results

383 paediatricians participated (79.8% response rate). Most were male (87.7%), aged 35 years or less (55.4%), working in tertiary care hospitals (68.4%) and undertaking 51–100 child consultations every day (45%). Only 15% reported obtaining training on antibiotic usage, AMR and/or antimicrobial stewardship. Only 7.6% confirmed functional antimicrobial stewardship programmes in their institutions. Most had adequate knowledge of antibiotic use and AMR. However, key issues were not fully understood with only 27.4% believing antibiotics were being overused among children. Paediatricians with less experience, and who undertook fewer consultations per day, had significantly lower knowledge scores. Most participants were prepared to initiate antimicrobial stewardship programmes; however, perceived barriers included a lack of online learning sources, treatment guidelines and support from hospital administration.

Discussion

Paediatricians had appropriate knowledge about antibiotic use and AMR although concerns with antibiotic use. Important barriers to integrating antimicrobial stewardship programmes were identified, which need addressing for these to become routine.
Back to Basics: Unraveling the Fundamentals of Lateral Flow Assays
Authors: Restrepo-Cano Valentina , García-Huertas Paola , Caraballo-Guzmán Arley , Sánchez-Jiménez Miryan M , Torres-Lindarte Giovanny
Published: December 2024

Background

Lateral flow assay (LFA) is a rapid analytical technique that has been implemented as a point-of-care approach for analyte detection. Given the rapid expansion of the use of LFA as a point-of-care testing strategy, LFA development has been subjected to extensive research, which has resulted in upgraded designs and technologies, improving levels of specificity and costs associated with manufacturing. This has allowed LFA to become an important option in rapid testing while maintaining appropriate limits of detection for accurate diagnoses.

Content

This review focuses on the theoretical basis of LFA, its components, formats, multiparametric possibilities, labels, and applications. Also, challenges associated with the technique and possible solutions are explored.

We explore LFA as a detection technique, its benefits, opportunities for improvement, and applications, and how challenges to its design can be approached.
Development of a Modified QuEChERS Extraction for the Detection of Rosemary Extracts (E392) Expressed as Sum of Carnosol and Carnosic Acid in Food by LC-MS/MS
Authors: Wong Yiu-Tung , Leung Tak-Shing , Fung Wai-Hong
Published: December 2024

Background

Rosemary extracts are derived from the leaves of Rosmarinus officinalis and commonly employed as a natural food preservative. They serve as natural antioxidants in food, preventing spoilage and extending shelf life.

Objective

This study aimed to develop a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction with liquid chromatography tandem mass spectrometry (LC-MS/MS) for the analysis of rosemary extracts in food as the sum of its markers carnosol and carnosic acid.

Method

Carnosol and carnosic acid in food were extracted by a modified QuEChERS extraction after the addition of analyte protectants during extraction and analyzed by LC-MS/MS via an internal standard calibration method. 2,2'-isopropylidienediphenol and podocarpic acid were used as internal standards for carnosol and carnosic acid, respectively.

Results

The limit of detection (LOD) of carnosol and carnosic acid were all less than 1 mg/kg, while their corresponding values of limit of quantitation (LOQ) ranged from 1.44 to 3.12 mg/kg in various matrixes. Spike recoveries at three fortification levels (10, 50, and 300 mg/kg) were all within 90–110% with RSD less than 10% in all cases.

Conclusions

A modified QuEChERS extraction with LC-MS/MS detection for the analysis of rosemary extracts in food was successfully developed, validated, and demonstrated to be fast, robust, and reliable.

Highlights

The developed modified QuEChERS extraction with LC-MS/MS detection offered a fast and efficient way to analyze rosemary extracts in various foods during a routine food surveillance program.
Validation of Enzytec™ Liquid Combi Sucrose/D-Glucose for Enzymatic Determination of Sucrose and D-Glucose in Selected Foods and Beverages: First Action 2024.05
Authors: Lacorn Markus , Hektor Thomas
Published: December 2024

Background

Sucrose is produced in the greatest quantity of all industrially produced organic substances and can be used in almost all processed foods. Glucose is the most abundant monosaccharide and contained in many foodstuffs naturally or added as an ingredient.

Objective

To validate the performance of the Enzytec™ Liquid Combi Sucrose/D-Glucose test kit for the determination of sucrose and D-glucose in juices, chocolate, breakfast cereals, ice cream, sweetened condensed milk, wine, beer, and soft drinks.

Methods

The kit contains all reagents in a ready-to-use format and is suitable for automation. Sucrose is cleaved by β-fructosidase. The resulting D-glucose from sucrose and glucose originally in the sample are phosphorylated and react in a NADH-generating reaction afterwards. β-Fructosidase is not present in the glucose system. The amount of NADH produced is equivalent to the amounts of sucrose and D-glucose and is measured at 340 nm within 30 min.

Results

The linear measurement range for a 100 µL test volume is from 17 to 2500 mg/L sucrose and 4 to 2000 mg/L D-glucose. Trueness was checked by using four Certified Reference Materials (CRM) and resulted in recoveries from 96 to 105%. Spiking of juices, ice cream, sweetened condensed milk, and shandy resulted in recoveries between 98 and 106% for both systems. Intermediate precision was 3% or lower for sucrose and glucose. For automation, three applications with different test volumes were validated. Linearity is given from 3.8 to 9500 mg/L for sucrose and 2.4 up to 10000 mg/L for glucose.

Conclusion

The method is robust and accurate for manual and automated applications. The method was approved as an AOAC Official Method of Analysis℠.

Highlights

The ready-to-use components of the test kit have a shelf of at least 29 months.
Effect of inulin on small extracellular vesicles microRNAs in milk from dairy cows with subclinical mastitis
Authors: Yu Wanjie , Nan Xuemei , Schroyen Martine , Wang Yue , Zhou Mengting , Tang Xiangfang , Xiong Benhai
Published: December 2024

Milk contains microRNAs (miRNA) that are shielded by small extracellular vesicles (sEVs). Beyond variations among individuals, many factors including nutrition play a role in shaping miRNA expression profiles. This study is to explore milk-derived sEVs-miRNA variations induced by inulin supplementation in subclinical mastitis-suffering cows. Fourteen lactating cows diagnosed with subclinical mastitis were equally assigned to either an inulin or a control group. Apart from total mixed rations, cows in the inulin group were provided with 300 g/d inulin during the morning feeding, while the control group did not receive any supplement. Following 1 wk of adaptation and 5 wk of treatment, sEVs-miRNA were isolated from the milk of each cow. RNA is subjected to high-throughput sequencing and differentially expressed (DE) miRNA (P < 0.05 and ∣ log2FC∣> 1) were detected through bioinformatics analysis. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to examine the target genes of DE miRNA. A sum of 350 miRNA was discovered, including 332 in the control group and 249 in the inulin group. Among these, 9 miRNA showed differential expression within the 2 groups, including 3 upregulated and 6 downregulated in the inulin group. The DE miRNA participates in regulating organismal systems, cellular processes, and signal transduction, which may affect inflammatory response and milk production. Overall, our study provides insight into the micromolecular-level mechanism of inulin in alleviating subclinical mastitis in dairy cows.
Identification of transcriptional regulators and signaling pathways mediating postnatal rumen growth and functional maturation in cattle
Authors: Pokhrel Binod , Tan Zhendong , Jiang Honglin
Published: December 2024

The rumen plays an essential role in the physiology and health of ruminants. The rumen undergoes substantial changes in size and function from birth to adulthood. The cellular and molecular mechanisms underlying these changes are not clear. This study aimed to identify the transcription factors (TFs) and signaling pathways mediating these changes in cattle. We found that the ratios of the emptied rumen, reticulum, omasum, and abomasum to body weight in adult steers were 4.8 (P < 0.01), 3.1 (P < 0.01), 6.0 (P < 0.01), and 0.8 (P = 0.9) times those in neonatal calves, respectively. The length of rumen papillae and the thickness of rumen epithelium, tunica mucosa and submucosa, tunica muscularis, and tunica serosa increased 7.4-, 2.0-, 3.0-, 2.9-, and 4.6-fold (P < 0.01 for all), respectively, from neonatal calves to adult steers. However, the density of rumen papillae was lower in adult steers than in neonatal calves (P < 0.05). The size of rumen epithelial cells was not different between neonatal calves and adult steers (P = 0.57). RNA sequencing identified 2,922 genes differentially expressed in the rumen between neonatal calves and adult steers. Functional enrichment analyses revealed that organ development, blood vessel development, Ras signaling, and Wnt signaling were among the functional terms enriched in genes downregulated in adult steers vs. neonatal calves and that fatty acid metabolism, immune responses, PPAR signaling, and Rap1 signaling were among those enriched in genes upregulated in adult steers vs. neonatal calves. Serum response factor (SRF), interferon regulatory factor 4, and purine-rich single-stranded DNA-binding protein alpha were among the major candidate TFs controlling the expression of genes upregulated, while TCF4, inhibitor of DNA binding 4, and snail family transcriptional repressor 2 were among those controlling the expression of genes downregulated in adult steers vs. neonatal calves. Taken together, these results suggest that the rumen grows by increasing the number, not the size, of cells from birth to adulthood, that the absorptive, metabolic, immune, and motility functions of the rumen are acquired or significantly enhanced during the postnatal life, and that the changes in rumen size and function from birth to adulthood are mediated by many candidate TFs, including SRF and TCF4, and many candidate signaling pathways, including the PPAR and Wnt signaling pathways.
Alleviation of lipopolysaccharide-induced heart inflammation in poultry treated with carnosic acid via the NF-κB and MAPK pathways
Authors: Liu Sirui , Liang Wanqing , Wu Jiaxin , Bao Endong , Tang Shu
Published: December 2024

In intensive poultry farming, environmental stress, pathogen infections, and noise can negatively impact growth or cause sudden death, leading to economic losses. The prevalent use of antibiotics as feed additives to prevent diseases in broilers has raised concerns about antibiotic resistance and highlighted the need for safer and more effective alternatives. Carnosic acid (CA), a bioactive compound derived from rosemary, exhibits notable pharmacological properties, including anti-inflammatory and antioxidant effects. This study investigates CA’s efficacy in mitigating lipopolysaccharide (LPS)-induced heart inflammation in broilers. Broilers were pretreated with CA at varying doses (20, 40, and 80 mg/kg) for 7 days then exposed to LPS (200 mg/kg) for 24h to induce an inflammatory response. LPS treatment increased the levels of the cardiac damage markers creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) and inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS), but these effects were markedly decreased in CA-pretreated poultry. Histopathological analysis indicated that CA mitigated myocardial fiber rupture and inflammatory cell infiltration. Immunohistochemistry showed that CA sustained high expression levels of the protective protein crystallin alpha B (CRYAB), the expression of which was reduced by LPS. Mechanistic studies demonstrated that CA regulates key inflammatory signaling pathways via inhibiting LPS-induced activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) by reducing the phosphorylation of p65 and inhibitor of nuclear factor kappa-B alpha (IκBα). Additionally, CA attenuated mitogen-activated protein kinase (MAPK) pathway activation, as evidenced by decreased phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 in the CA-treated groups compared to the LPS-only groups. These findings suggest that CA exerts a protective effect against LPS-induced cardiac inflammation by enhancing CRYAB expression and modulating the NF-κB and MAPK pathways. Importantly, the findings emphasize CA’s potential as a natural feed additive to enhance cardiac health in poultry and present a promising alternative to conventional antibiotics in livestock management. Further research is needed to investigate its broader applications in animal health and other inflammatory conditions.
Export-Led Decay: The Trade Channel in the Gold Standard Era
Authors: Candia Bernardo , Pedemonte Mathieu
Published: December 2024

Flexible exchange rates can facilitate price adjustments that buffer macroeconomic shocks. We test this hypothesis using adjustments to the gold standard during the Great Depression. Using novel monthly data on city-level economic activity, sectoral employment, and export data, we show that American exporting cities were significantly affected by changes in bilateral exchange rates. We calibrate a general equilibrium model to obtain aggregate effects from cross-sectional estimates. We show that the trade channel deepened the Great Depression and was a key driver of the economic recovery in 1933.