bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantification of neurofilament light and glial fibrillary acidic protein in finger-prick blood
Authors: Kolanko Magdalena A , Huber Hanna , David Michael C B , Montoliu-Gaya Laia , Simrén Joel , Blennow Kaj , Zetterberg Henrik , Nilforooshan Ramin , Malhotra Paresh , Sharp David J , Ashton Nicholas J , Graham Neil S N
Published: April 2024

An accurate diagnosis of neurodegenerative disease and traumatic brain injury is important for prognostication and treatment. Neurofilament light and glial fibrillary acidic protein (GFAP) are leading biomarkers for neurodegeneration and glial activation that are detectable in blood. Yet, current recommendations require rapid centrifugation and ultra-low temperature storage post-venepuncture. Here, we investigated if these markers can be accurately measured in finger-prick blood using dried plasma spot cards. Fifty patients (46 with dementia; 4 with traumatic brain injury) and 19 healthy volunteers underwent finger-prick and venous sampling using dried plasma spot cards and aligned plasma sampling. Neurofilament light and GFAP were quantified using a Single molecule array assay and correlations between plasma and dried plasma spot cards assessed. Biomarker concentrations in plasma and finger-prick dried plasma spot samples were significantly positively correlated (neurofilament light ρ = 0.57; GFAP ρ = 0.58, P < 0.001). Finger-prick neurofilament light and GFAP were significantly elevated after acute traumatic brain injury with non-significant group-level increases in dementia (91% having Alzheimer’s disease dementia). In conclusion, we present preliminary evidence that quantifying GFAP and neurofilament light using finger-prick blood collection is viable, with samples stored at room temperature using dried plasma spot cards. This has potential to expand and promote equitable testing access, including in settings where trained personnel are unavailable to perform venepuncture.
Spike-induced cytoarchitectonic changes in epileptic human cortex are reduced via MAP2K inhibition
Authors: Smith Rachael A , Mir Fozia , Butler Mitchell P , Maharathi Biswajit , Loeb Jeffrey A
Published: April 2024

Interictal spikes are electroencephalographic discharges that occur at or near brain regions that produce epileptic seizures. While their role in generating seizures is not well understood, spikes have profound effects on cognition and behaviour, depending on where and when they occur. We previously demonstrated that spiking areas of human neocortex show sustained MAPK activation in superficial cortical Layers I–III and are associated with microlesions in deeper cortical areas characterized by reduced neuronal nuclear protein staining and increased microglial infiltration. Based on these findings, we chose to investigate additional neuronal populations within microlesions, specifically inhibitory interneurons. Additionally, we hypothesized that spiking would be sufficient to induce similar cytoarchitectonic changes within the rat cortex and that inhibition of MAPK signalling, using a MAP2K inhibitor, would not only inhibit spike formation but also reduce these cytoarchitectonic changes and improve behavioural outcomes. To test these hypotheses, we analysed tissue samples from 16 patients with intractable epilepsy who required cortical resections. We also utilized a tetanus toxin-induced animal model of interictal spiking, designed to produce spikes without seizures in male Sprague–Dawley rats. Rats were fitted with epidural electrodes, to permit EEG recording for the duration of the study, and automated algorithms were implemented to quantify spikes. After 6 months, animals were sacrificed to assess the effects of chronic spiking on cortical cytoarchitecture. Here, we show that microlesions may promote excitability due to a significant reduction of inhibitory neurons that could be responsible for promoting interictal spikes in superficial layers. Similarly, we found that the induction of epileptic spikes in the rat model produced analogous changes, including reduced neuronal nuclear protein, calbindin and parvalbumin-positive neurons and increased microglia, suggesting that spikes are sufficient for inducing these cytoarchitectonic changes in humans. Finally, we implicated MAPK signalling as a driving force producing these pathological changes. Using CI-1040 to inhibit MAP2K, both acutely and after spikes developed, resulting in fewer interictal spikes, reduced microglial activation and less inhibitory neuron loss. Treated animals had significantly fewer high-amplitude, short-duration spikes, which correlated with improved spatial memory performance on the Barnes maze. Together, our results provide evidence for a cytoarchitectonic pathogenesis underlying epileptic cortex, which can be ameliorated through both early and delayed MAP2K inhibition. These findings highlight the potential role for CI-1040 as a pharmacological treatment that could prevent the development of epileptic activity and reduce cognitive impairment in both patients with epilepsy and those with non-epileptic spike-associated neurobehavioural disorders.
Resting-state functional connectivity in children cooled for neonatal encephalopathy
Authors: Spencer Arthur P C , Goodfellow Marc , Chakkarapani Ela , Brooks Jonathan C W
Published: April 2024

Therapeutic hypothermia improves outcomes following neonatal hypoxic-ischaemic encephalopathy, reducing cases of death and severe disability such as cerebral palsy compared with normothermia management. However, when cooled children reach early school-age, they have cognitive and motor impairments which are associated with underlying alterations to brain structure and white matter connectivity. It is unknown whether these differences in structural connectivity are associated with differences in functional connectivity between cooled children and healthy controls. Resting-state functional MRI has been used to characterize static and dynamic functional connectivity in children, both with typical development and those with neurodevelopmental disorders. Previous studies of resting-state brain networks in children with hypoxic-ischaemic encephalopathy have focussed on the neonatal period. In this study, we used resting-state fMRI to investigate static and dynamic functional connectivity in children aged 6–8 years who were cooled for neonatal hypoxic-ischaemic without cerebral palsy [n = 22, median age (interquartile range) 7.08 (6.85–7.52) years] and healthy controls matched for age, sex and socioeconomic status [n = 20, median age (interquartile range) 6.75 (6.48–7.25) years]. Using group independent component analysis, we identified 31 intrinsic functional connectivity networks consistent with those previously reported in children and adults. We found no case-control differences in the spatial maps of these intrinsic connectivity networks. We constructed subject-specific static functional connectivity networks by measuring pairwise Pearson correlations between component time courses and found no case-control differences in functional connectivity after false discovery rate correction. To study the time-varying organization of resting-state networks, we used sliding window correlations and deep clustering to investigate dynamic functional connectivity characteristics. We found k = 4 repetitively occurring functional connectivity states, which exhibited no case-control differences in dwell time, fractional occupancy or state functional connectivity matrices. In this small cohort, the spatiotemporal characteristics of resting-state brain networks in cooled children without severe disability were too subtle to be differentiated from healthy controls at early school-age, despite underlying differences in brain structure and white matter connectivity, possibly reflecting a level of recovery of healthy resting-state brain function. To our knowledge, this is the first study to investigate resting-state functional connectivity in children with hypoxic-ischaemic encephalopathy beyond the neonatal period and the first to investigate dynamic functional connectivity in any children with hypoxic-ischaemic encephalopathy.
Remarkably facilitated crystallization of MSE-type zeolite by using an efficient organic structure-directing agent
Authors: Nakamura Kaisei , Okubo Kai , Takaoka Fumiya , Zhang Shengxiang , Inagaki Satoshi , Kubota Yoshihiro
Published: April 2024

A very powerful organic structure-directing agent (OSDA) for the synthesis of MSE-type zeolite was designed and successfully prepared. When using conventional OSDA, more than 10 d of crystallization time was necessary, whereas the use of the new type of OSDA gave a highly crystalline MSE-type zeolite using only 32 h of crystallization time.
Expression of inducible nitric oxide synthase, nitrotyrosine, eosinophilic peroxidase, eotaxin-3, and galectin-3 in patients with gastroesophageal reflux disease, eosinophilic esophagitis, and in healthy controls: a semiquantitative image analysis of 3,3′-diaminobenzidine-stained esophageal biopsies
Authors: Plate John , Bove Mogens , Larsson Helen M , Norder Grusell Elisabeth , Chatterjee Nabanita , Johansson Leif E , Bergquist Henrik
Published: April 2024

Eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) share many histopathological features; therefore, markers for differentiation are of diagnostic interest and may add to the understanding of the underlying mechanisms. The nitrergic system is upregulated in GERD and probably also in EoE. Esophageal biopsies of patients with EoE (n = 20), GERD (n = 20), and healthy volunteers (HVs) (n = 15) were exposed to antibodies against inducible nitric oxide synthase (iNOS), nitrotyrosine, eosinophilic peroxidase, eotaxin-3, and galectin-3. The stained object glasses were randomized, digitized, and blindly analyzed regarding the expression of DAB (3,3′-diaminobenzidine) by a protocol developed in QuPath software. A statistically significant overexpression of iNOS was observed in patients with any of the two inflammatory diseases compared with that in HVs. Eotaxin-3 could differentiate HVs versus inflammatory states. Gastroesophageal reflux patients displayed the highest levels of nitrotyrosine. Neither iNOS nor nitrotyrosine alone were able to differentiate between the two diseases. For that purpose, eosinophil peroxidase was a better candidate, as the mean levels increased stepwise from HVs via GERD to EoE. iNOS and nitrotyrosine are significantly overexpressed in patients with EoE and GERD compared with healthy controls, but only eosinophil peroxidase could differentiate the two types of esophagitis. The implications of the finding of the highest levels of nitrotyrosine among gastroesophageal reflux patients are discussed.
Preoperative smoking status and long-term survival after coronary artery bypass grafting: a competing risk analysis
Authors: Abreu Armando , Máximo José , Leite-Moreira Adelino
Published: April 2024

OBJECTIVES

Patients with severe coronary artery disease who undergo coronary artery bypass grafting consistently demonstrate that continued smoking after surgery increases late mortality rates. Smoking may exert its harmful effects through the ongoing chronic process of atherosclerotic progression both in the grafts and the native system. However, it is not clear whether cardiac mortality is primary and solely responsible for the inferior late survival of current smokers.

METHODS

In this retrospective analysis, we included all consecutive patients undergoing primary isolated coronary artery bypass surgery from 1 January 2000 to 30 September 2015 in an Academic Hospital in Northern Portugal. The predictive or independent variable was the patients' smoking history status, a categorical variable with 3 levels: non-smoker (the comparator), ex-smoker for >1 year (exposure 1) and current smoker (exposure 2). The primary end point was long-term all-cause mortality. Secondary outcomes were long-term cause-specific mortality (cardiovascular and noncardiovascular). We fitted overall and Fine and Gray subdistribution hazard models.

RESULTS

We identified 5242 eligible patients. Follow-up was 99.7% complete (with 17 patients lost to follow-up). The median follow-up time was 12.79 years (interquartile range, 9.51–16.60). Throughout the study, there were 2049 deaths (39.1%): 877 from cardiovascular causes (16.7%), 727 from noncardiovascular causes (13.9%) and 445 from unknown causes (8.5%). Ex-smokers had an identical long-term survival than non-smokers [hazard ratio (HR) 0.99; 95% confidence interval (CI) 0.88, 1.12; P = 0.899]. Conversely, current smokers had a 24% increase in late mortality risk (HR 1.24; 95% CI 1.07, 1.44; P = 0.004) as compared to non-smokers. While the current smoker status increased the relative incidence of noncardiac death by 61% (HR 1.61; 95% CI 1.27, 2.05, P < 0.001), it did confer a 25% reduction in the relative incidence of cardiac death (HR 0.75; 95% CI 0.59, 0.97; P = 0.025).

CONCLUSIONS

Whereas ex-smokers have an identical long-term survival to non-smokers, current smokers exhibit an increase in late all-cause mortality risk at the expense of an increased relative incidence of noncardiac death. By subtracting the inciting risk factor, smoking cessation reduces the relative incidence of cardiac death.
Validation of a machine learning algorithm to identify pulmonary vein isolation during ablation procedures for the treatment of atrial fibrillation: results of the PVISION study
Authors: De Pooter Jan , Timmers Liesbeth , Boveda Serge , Combes Stephane , Knecht Sebastien , Almorad Alexandre , De Asmundis Carlos , Duytschaever Mattias
Published: April 2024

Aims

Pulmonary vein isolation (PVI) is the cornerstone of ablation for atrial fibrillation. Confirmation of PVI can be challenging due to the presence of far-field electrograms (EGMs) and sometimes requires additional pacing manoeuvres or mapping. This prospective multicentre study assessed the agreement between a previously trained automated algorithm designed to determine vein isolation status with expert opinion in a real-world clinical setting.

Methods and results

Consecutive patients scheduled for PVI were recruited at four centres. The ECGenius electrophysiology (EP) recording system (CathVision ApS, Copenhagen, Denmark) was connected in parallel with the existing system in the laboratory. Electrograms from a circular mapping catheter were annotated during sinus rhythm at baseline pre-ablation, time of isolation, and post-ablation. The ground truth for isolation status was based on operator opinion. The algorithm was applied to the collected PV signals off-line and compared with expert opinion. The primary endpoint was a sensitivity and specificity exceeding 80%. Overall, 498 EGMs (248 at baseline and 250 at PVI) with 5473 individual PV beats from 89 patients (32 females, 62 ± 12 years) were analysed. The algorithm performance reached an area under the curve (AUC) of 92% and met the primary study endpoint with a sensitivity and specificity of 86 and 87%, respectively (P = 0.005; P = 0.004). The algorithm had an accuracy rate of 87% in classifying the time of isolation.

Conclusion

This study validated an automated algorithm using machine learning to assess the isolation status of pulmonary veins in patients undergoing PVI with different ablation modalities. The algorithm reached an AUC of 92%, with both sensitivity and specificity exceeding the primary study endpoints.
Lipid changes and volatile compounds formation in different processing stages of dry-cured Spanish mackerel
Authors: Wang Shanyu , Jian Chong , Hu Mengyue , Zhao Ling , Sun Huihui , Liu Qi , Cao Rong , Xue Yong
Published: April 2024

Objectives

This study delves into the alterations in lipids and major flavor compounds occurring throughout various drying stages (raw fish, dry-cured for 4, 8, and 12 d) of dry-cured Spanish mackerel (DCSM) and elucidates the mechanism underlying their formation.

Materials and Methods

In this paper, we used Thin Layer Chromatography and Headspace Gas Chromatography-Ion Mobility Spectrometry to determine the changes in lipid and volatile substances during the drying process of Spanish mackerel.

Results

The phospholipid, triacylglycerol, heptanal, t-2-hexenal, and dimethyl disulfide contents were notably lower in the samples collected 4 d before processing. The peroxide value and thiobarbituric acid reactive substances significantly increased after 4–8 d, concomitant with the generation of numerous volatile compounds, including alcohols, aldehydes, and ketones. Substantial quantities of 2-methylbutyraldehyde, thiazole, butyl acetate, and trimethylpyrazine emerged during the 8–12 d processing phase. Furthermore, C18:1n-9, C20:5n-3, and C22:6n-3 demonstrated noteworthy correlations with the development of 21 compounds. Principal component analysis, grounded in lipid and volatile compound content, adeptly classified the DCSM drying process into lipolysis and flavor preparation (0–4 d), lipid oxidation and flavor formation (4–8 d), and maturation (8–12 d). The ripening stage played a crucial role in shaping the comprehensive flavor profile.

Conclusion

This study offers valuable insights to enhance traditional DCSM flavor processing and regulation.
Paving the path for implementation of clinical genomic sequencing globally: Are we ready?
Authors: Marshall Deborah A , Hua Nicolle , Buchanan James , Christensen Kurt D , Frederix Geert W J , Goranitis Ilias , Ijzerman Maarten , Jansen Jeroen P , Lavelle Tara A , Regier Dean A , Smith Hadley S , Ungar Wendy J , Weymann Deirdre , Wordsworth Sarah , Phillips Kathryn A
Published: April 2024

Despite the emerging evidence in recent years, successful implementation of clinical genomic sequencing (CGS) remains limited and is challenged by a range of barriers. These include a lack of standardized practices, limited economic assessments for specific indications, limited meaningful patient engagement in health policy decision-making, and the associated costs and resource demand for implementation. Although CGS is gradually becoming more available and accessible worldwide, large variations and disparities remain, and reflections on the lessons learned for successful implementation are sparse. In this commentary, members of the Global Economics and Evaluation of Clinical Genomics Sequencing Working Group (GEECS) describe the global landscape of CGS in the context of health economics and policy and propose evidence-based solutions to address existing and future barriers to CGS implementation. The topics discussed are reflected as two overarching themes: (1) system readiness for CGS and (2) evidence, assessments, and approval processes. These themes highlight the need for health economics, public health, and infrastructure and operational considerations; a robust patient- and family-centered evidence base on CGS outcomes; and a comprehensive, collaborative, interdisciplinary approach.
The impact of cardiopulmonary bypass time on the Sequential Organ Failure Assessment score after cardiac surgery
Authors: Velho Tiago R , Pereira Rafael Maniés , Guerra Nuno Carvalho , Ferreira Ricardo , Pedroso Dora , Neves-Costa Ana , Nobre Ângelo , Moita Luís Ferreira
Published: April 2024

OBJECTIVES

Postoperative organ dysfunction is common after cardiac surgery, particularly when cardiopulmonary bypass (CPB) is used. The Sequential Organ Failure Assessment (SOFA) score is validated to predict morbidity and mortality in cardiac surgery. However, the impact of CPB duration on postoperative SOFA remains unclear.

METHODS

This is a retrospective study. Categorical values are presented as percentages. The comparison of SOFA groups utilized the Kruskal–Wallis chi-squared test, complemented by ad hoc Dunn’s test with Bonferroni correction. Multinomial logistics regressions were employed to evaluate the relationship between CPB time and SOFA.

RESULTS

A total of 1032 patients were included. CPB time was independently associated with higher postoperative SOFA scores at 24 h. CPB time was significantly higher in patients with SOFA 4–5 (**P = 0.0022) or higher (***P < 0.001) when compared to SOFA 0–1. The percentage of patients with no/mild dysfunction decreased with longer periods of CPB, down to 0% for CPB time >180min (50% of the patients with >180m in of CPB presented SOFA ≥ 10). The same trend is observed for each of the SOFA variables, with higher impact in the cardiovascular and renal systems. Severe dysfunction occurs especially >200 min of CPB (cardiovascular system >100 min; other systems mainly >200 min).

CONCLUSIONS

CPB time may predict the probability of postoperative SOFA categories. Patients with extended CPB durations exhibited higher SOFA scores (overall and for each variable) at 24 h, with higher proportion of moderate and severe dysfunction with increasing times of CPB.
Community pharmacy discharge medicines service activity as recorded in PharmOutcomes: a retrospective exploration and analysis
Authors: Wilcock Michael , Bastian Liam , Jones Anne , Baqir Wasim
Published: April 2024

Objectives

Transition of care when a patient moves between healthcare locations is a risk factor for medication errors and medicines-related preventable harm. The aims of this retrospective service evaluation were to understand, by classifying and quantifying, the nature of interventions made by community pharmacy when receiving a discharge medicines service referral from a secondary care hospital, with a focus on two groups of high-risk medicines supplied at discharge—oral anticoagulants and weak opioids following hip or knee surgery.

Methods

Records made on the PharmOutcomes™ platform by community pharmacists in response to referral for the NHS England discharge medicines service were analysed and summarized. This analysis was exploratory and interpretative in nature and used a convenience sample of patients who had consented for the service over 12 months from May 2022 to April 2023.

Key findings

During 12 months, 6811 referrals occurred, of which 71% were recorded as having different stages of the service completed on PharmOutcomes™. Medicines reconciliation, first-prescription review, and consultation stages decreased as patients progressed through the service. Slightly greater rates of completion were observed for patients receiving oral anticoagulants and for codeine or dihydrocodeine following hip and knee surgery, although overall referrals were low for this latter cohort.

Conclusions

Through this service, community pharmacists are well placed to support the safe and effective use of medicines including oral anticoagulants and weak opioids posthospital discharge and potentially reduce incidents of avoidable harm. The variations in recorded completion rates across the three stages of the service and the apparent greater finalization rates for the high-risk medicines studied require further investigation.
Antibiofilm Agents for the Treatment and Prevention of Bacterial Vaginosis: A Systematic Narrative Review
Authors: Gao Michael , Manos Jim , Whiteley Greg , Zablotska-Manos Iryna
Published: April 2024

Background

Bacterial vaginosis (BV) is difficult to eradicate due to BV biofilms protecting BV bacteria (Gardnerella, Prevotella, and other genera). With the growing understanding of biofilms, we systematically reviewed the current knowledge on the efficacy of anti-BV biofilm agents.

Methods

We searched literature in the Scopus, Medline, and Embase databases for empirical studies investigating substances for the treatment of BV biofilms or prevention of their recurrence and their efficacy and/or safety.

Results

Of 201 unique titles, 35 satisfied the inclusion criteria. Most studies (89%) reported on preclinical laboratory research on the efficacy of experimental antibiofilm agents (80%) rather than their safety. Over 50% were published within the past 5 years. Agents were classified into 7 groups: antibiotics, antiseptics, cationic peptides, enzymes, plant extracts, probiotics, and surfactants/surfactant components. Enzymes and probiotics were most commonly investigated. Earlier reports of antibiotics having anti-BV biofilm activity have not been confirmed. Some compounds from other classes demonstrated promising anti-BV biofilm efficacy in early studies.

Conclusions

Further research is anticipated on successful antibiofilm agents. If confirmed as effective and safe in human clinical trials, they may offer a breakthrough in BV treatment. With rising antibiotic resistance, antibiofilm agents will significantly improve the current standard of care for BV management.
Comparison of carbapenem MIC for NDM-producing Enterobacterales by different AST methods
Authors: Lee Alfred Lok Hang , Leung Eddie Chi Man , Chow Viola Chi Ying
Published: April 2024

Introduction

This study compared the performance of MIC test strip (ETEST), automated AST card (Vitek 2) and broth microdilution (BMD) in determining carbapenem susceptibility and MIC values of NDM-producing Enterobacterales.

Methods

NDM-producing Enterobacterales recovered from clinical specimens were included. The presence of blaNDM was confirmed by PCR. Identification of bacterial isolates was done by MALDI-TOF. Phenotypic susceptibility to three carbapenems (ertapenem, imipenem and meropenem) was tested by BMD, ETEST and Vitek 2. MIC values were interpreted in accordance with CLSI M100 (2022 edition). Using BMD as the reference standard, the essential agreement (EA), categorical agreement (CA), very major error (VME) and major error (ME) rates were evaluated.

Results

Forty-seven NDM-producing Enterobacterales isolates were included, 44 of which were Escherichia coli. The EA of Vitek 2 was 97.9% for ertapenem, 25.5% for meropenem and 42.6% for imipenem. Using Vitek 2, there were 0% VMEs across all three carbapenems tested. The EA of ETEST was 53.2% for ertapenem, 55.3% for imipenem and 36.2% for meropenem. The rates of VMEs for ETEST were high too (ertapenem 8.5%, meropenem 36.2%, imipenem 26.1%). The MIC values obtained from Vitek 2 were consistently higher than those from BMD, while MICs from ETEST were consistently lower than those from BMD.

Conclusions

The VME rate for ETEST was unacceptably high when BMD was used as the standard for comparison. Vitek 2 had acceptable EA and CA for ertapenem when BMD was used as the standard for comparison. For meropenem and imipenem, neither of the methods (ETEST, Vitek 2) showed acceptable EA and CA when compared with BMD.
Effects of dietary water-soluble extract of rosemary supplementation on growth performance and intestinal health of broilers infected with Eimeria tenella
Authors: Peng Fang , Duan Jiaqi , He Xi , Xie Kun , Song Zehe
Published: April 2024

This study was conducted to explore the effect of dietary supplementation of water-soluble extract of rosemary (WER) on growth performance and intestinal health of broilers infected with Eimeria tenella (E. tenella), and evaluate the anticoccidial activity of WER. 360 1-d-old Chinese indigenous male yellow-feathered broiler chickens were randomly allocated to six groups: blank control (BC) group and infected control (IC) group received a basal diet; positive control (PC) group, received a basal diet supplemented with 200 mg/kg diclazuril; WER100, WER200, and WER300 groups received a basal diet containing 100, 200, and 300 mg/kg WER, respectively. On day 21, all birds in the infected groups (IC, PC, WER100, WER200, and WER300) were orally gavaged with 1 mL phosphate-buffered saline (PBS) of 8 × 104 sporulated oocysts of E. tenella, and birds in the BC group were administrated an aliquot of PBS dilution. The results showed that dietary supplementation of 200 mg/kg WER increased the average daily gain of broilers compared to the IC group from days 22 to 29 (P < 0.001). The anticoccidial index values of 100, 200, and 300 mg/kg WER were 137.49, 157.41, and 144.22, respectively, which indicated that WER exhibited moderate anticoccidial activity. Compared to the IC group, the groups supplemented with WER (100, 200, and 300 mg/kg) significantly lowered fecal oocyst output (P < 0.001) and cecal coccidia oocysts, alleviated intestinal damage and maintained the integrity of intestinal epithelium. Dietary supplementation with WER significantly improved antioxidant capacity, elevated the levels of secretory immunoglobulin A, and diminished inflammation within the cecum, particularly at a dosage of 200 mg/kg. The results of this study indicated that dietary supplementation with 200 mg/kg WER could improve broiler growth performance and alleviate intestinal damage caused by coccidiosis.
Seasonal migration pattern of an important rice pest, Nilaparvata lugens (Hemiptera: Delphacidae), on Hainan Island, China
Authors: Gu Fuxiong , Lu Hui , Lyu Baoqian , Zhang Qikai , Jiao Bin , Tang Jihong
Published: April 2024

The brown planthopper, Nilaparvata lugens (Hemiptera: Delphacidae) (BPH), is a major, regionally migratory pest of rice in Asia. Despite intensive migratory studies, the seasonal migratory pattern of this species in the year-round breeding region (i.e., Hainan Island) remains largely unknown. To understand the migration dynamics, we conducted relevant research based on BPH light trap catches on Hainan in 2017–2022. Results showed that the occurrence dynamics of BPH in Hainan oscillated in different years and seasons. Overall, there are 4 migration peak periods on Hainan, with outbound peak periods in April–May and August–September and inbound peak periods in June and October. Trajectory and wind fields showed that in August–September, Hainan had complex meteorological conditions, and the outbound paths of BPH were variable, mainly landing in southeastern Guangxi and southwestern Guangdong. In contrast, April–May was influenced by southeasterly winds, with a wider outbound range and a further distance, landing along northeastern Vietnam from west to east toward Guangxi and Guangdong areas with time. Wind-rain fields, trajectory, and hydrogen isotope showed that in June, southwesterly winds transported BPH northward from the Indochina peninsula, where it was hindered by rainfall in the Leizhou Peninsula area and the migrants will be “rained out” into Hainan. Identically, in October, the interactions between northeasterly winds and rainfall belts on the southwest shore of Hainan increased the opportunities for BPH to migrate southward to reach Hainan. Our results suggest that Hainan is not only an important source of BPH migrating from East Asia but also plays the role of a bridge.
Not just for lymphoid cells: the role of the noncanonical NF-κB signaling pathway in early and late myelopoiesis with a focus on hypereosinophilic disorders
Authors: Trusiano Brie , Zimmerman Kurt L , Morrison Holly A , Allen Irving C
Published: April 2024

The noncanonical NF-κB pathway is involved in lymphoid organ development, B-cell maturation, and cytokine production. However, new research has demonstrated that this pathway is also key for the orderly and sequential maturation of myeloid cells, including neutrophils and eosinophils. When this pathway is disrupted or constitutively activated, aberrations in hematopoietic stem and progenitor cell survival and proliferation, as well as subsequent granulopoiesis and eosinophilopoiesis, are affected. Disturbance of such a coordinated and delicate process can manifest in devastating clinical disease, including acute and chronic myeloid leukemias, preleukemic processes such as myelodysplastic syndrome, or hyperinflammatory conditions like hypereosinophilic syndrome. In this review, we discuss the molecular machinery within the noncanonical NF-κB pathway, crosstalk with the canonical NF-κB pathway, murine models of noncanonical signaling, and how aberrations in this pathway manifest in leukemic or hyperinflammatory disease with a focus on hypereosinophilic syndrome. Potential and promising drug therapies will also be discussed, emphasizing the noncanonical NF-κB pathway as a potential target for improved treatment for patients with leukemia or idiopathic hypereosinophilic syndrome. The hope is that review of such mechanisms and treatments may eventually result in findings that aid physicians in rapidly diagnosing and more accurately classifying patients with such complex and overlapping hematopoietic diseases.
The regenerative liminalities of Global Citizenship Education
Authors: Palmer Nicholas
Published: April 2024

Global citizenship education (GCE) is an active entanglement in the civic priorities of the planet. In recent research, the concept has emerged as a multivalent coalescence of being, an engagement with planetary tensions and revisions of cosmopolitan ideology. In this article, I argue for a theoretical interpretation of GCE reliant on liminal-oriented practice and the potentialities of regenerative agency. Privileging Axel Honneth’s interpretation of social freedom and Boaventura de Sousa Santos’ postabyssal thinking, I argue that interfaces with the limit of our global perception reveal the regenerative qualities of our relations, allowing us to conceive ourselves as uniquely influenced by globality and possessing critical agency for otherness. Although such global perceptions can only ever be wrought within the ideological constraints of locality, a globally situated agency is more agile as a regenerative set of dispositions and interknowledge ‘globalities’. I further argue that regenerative liminalities hold significant implications for teaching and learning, as they signify the importance of a global consciousness over a technologically rationalized competency-based approach.
When digitalization hit the court: Strategizing to turn turbulence into opportunities
Authors: Kronblad Charlotta , Pregmark Johanna Envall
Published: April 2024

During Covid-19, the pace of digitalization in industry and society increased. This article zooms in on the court system in Sweden and its response to this rapidly changing context. During the pandemic, the courts had encountered new expectations, and digital technologies had been implemented at speed. Suddenly online trials and digital delivery of court services became a reality. When the pandemic eased questions arose whether to return to business-as-usual or to continue on the new digital path. This article builds on a series of strategic workshops performed at the Swedish courts 2020–23 (with a total of 200 professionals attending). We found that digitalization had affected core work processes as well as the mindset and culture for further change. However, strategic alignment of different organizational components to fit the new reality is still needed in order for the courts to keep, and develop, the largest gains from digitalization: flexibility, efficiency, and accessibility.
A recombinant plasmid encoding human hepatocyte growth factor promotes healing of combined radiation-trauma skin injury involved in regulating Nrf2 pathway in mice
Authors: Li Dujuan , Lu Yuxin , Xiao Fengjun , Cheng Xiaochen , Hu Chunsheng , Zhu Xuefeng , Wang Xiaoying , Duan Haiying , Du Li , Zhang Qinglin
Published: April 2024

Combined radiation-trauma skin injury represents a severe and intractable condition that urgently requires effective therapeutic interventions. In this context, hepatocyte growth factor (HGF), a multifunctional growth factor with regulating cell survival, angiogenesis, anti-inflammation and antioxidation, may be valuable for the treatment of combined radiation-trauma injury. This study investigated the protective effects of a recombinant plasmid encoding human HGF (pHGF) on irradiated human immortalized keratinocytes (HaCaT) cells in vitro, and its capability to promote the healing of combined radiation-trauma injuries in mice. The pHGF radioprotection on irradiated HaCaT cells in vitro was assessed by cell viability, the expression of Nrf2, Bcl-2 and Bax, as well as the secretion of inflammatory cytokines. In vivo therapeutic treatment, the irradiated mice with full-thickness skin wounds received pHGF local injection. The injuries were appraised based on relative wound area, pathology, immunohistochemical detection, terminal deoxynucleotidyl transferase dUTP nick end labelling assay and cytokine content. The transfection of pHGF increased the cell viability and Nrf2 expression in irradiated HaCaT cells. pHGF also significantly upregulated Bcl-2 expression, decreased the Bax/Bcl-2 ratio and inhibited the expression of interleukin-1β and tumor necrosis factor-α in irradiated cells. Local pHGF injection in vivo caused high HGF protein expression and noticeable accelerated healing of combined radiation-trauma injury. Moreover, pHGF administration upregulated Nrf2, vascular endothelial growth factor, Bcl-2 expression, downregulated Bax expression and mitigated inflammatory response. In conclusion, the protective effect of pHGF may be related to inhibiting apoptosis and inflammation involving by upregulating Nrf2. Local pHGF injection distinctly promoted the healing of combined radiation-trauma injury and demonstrates potential as a gene therapy intervention for combined radiation-trauma injury in clinic.
SMART: spectral energy distributions Markov chain analysis with radiative transfer models
Authors: Varnava Charalambia , Efstathiou Andreas
Published: April 2024

In this paper we present the publicly available open-source spectral energy distribution (SED) fitting code SMART (Spectral energy distributions Markov chain Analysis with Radiative Transfer models). Implementing a Bayesian Markov chain Monte Carlo (MCMC) method, SMART fits the ultraviolet to millimetre SEDs of galaxies exclusively with radiative transfer models that currently constitute four types of pre-computed libraries, which describe the starburst, active galactic nucleus (AGN) torus, host galaxy, and polar dust components. An important novelty of SMART is that, although it fits SEDs exclusively with radiative transfer models, it takes comparable time to popular energy balance methods to run. Here we describe the key features of SMART and test it by fitting the multiwavelength SEDs of the 42 local ultraluminous infrared galaxies (ULIRGs) that constitute the HERschel Ultraluminous Infrared Galaxy Survey (HERUS) sample. The Spitzer spectroscopy data of the HERUS ULIRGs are included in the fitting at a spectral resolution, which is matched to that of the radiative transfer models. We also present other results that highlight the performance and versatility of SMART. SMART promises to be a useful tool for studying galaxy evolution in the JWST era. SMART is developed in Python and is available at https://github.com/ch-var/SMART.git.
Tracing the green valley with entropic thresholding
Authors: Pandey Biswajit
Published: April 2024

The green valley represents the population of galaxies that are transitioning from the actively star-forming blue cloud to the passively evolving red sequence. Studying the properties of the green valley galaxies is crucial for our understanding of the exact mechanisms and processes that drive this transition. The green valley does not have a universally accepted definition. The boundaries of the green valley are often determined by empirical lines that are subjective and vary across studies. We present an unambiguous definition of the green valley in the colour–stellar mass plane using the entropic thresholding. We first divide the galaxy population into the blue cloud and the red sequence based on a colour threshold that minimizes the intraclass variance and maximizes the interclass variance. Our method splits the region between the mean colours of the blue cloud and the red sequence into three parts by maximizing the total entropy of that region. We repeat our analysis in a number of independent stellar mass bins to define the boundaries of the green valley in the colour–mass diagram. Our method provides a robust and natural definition of the green valley.
A dusty protocluster surrounding the binary galaxy HerBS-70 at z = 2.3
Authors: Bakx Tom J L C , Berta S , Dannerbauer H , Cox P , Butler K M , Hagimoto M , Hughes D H , Riechers D A , van der Werf P P , Yang C , Baker A J , Beelen A , Bendo G J , Borsato E , Buat V , Cooray A R , Dunne L , Dye S , Eales S , Gavazzi R , Harris A I , Ismail D , Ivison R J , Jones B , Krips M , Lehnert M D , Marchetti L , Messias H , Negrello M , Neri R , Omont A , Perez-Fournon I , Nanni A , Chartab N , Serjeant S , Stanley F , Tamura Y , Urquhart S A , Vlahakis C , Weiß A , Young A J
Published: April 2024

We report on deep SCUBA-2 observations at 850 $\mu$m and NOrthern Extended Millimetre Array (NOEMA) spectroscopic measurements at 2 mm of the environment surrounding the luminous, massive (M* ≈ 2 × 1011 M⊙) Herschel-selected source HerBS-70. This source was revealed by previous NOEMA observations to be a binary system of dusty star-forming galaxies at z = 2.3, with the east component (HerBS-70E) hosting an active galactic nucleus. The SCUBA-2 observations detected, in addition to the binary system, 21 sources at >3.5σ over an area of ∼25 square comoving Mpc with a sensitivity of 1σ850 = 0.75 mJy. The surface density of continuum sources around HerBS-70 is three times higher than for field galaxies. The NOEMA spectroscopic measurements confirm the protocluster membership of three of the nine brightest sources through their CO(4–3) line emission, yielding a volume density 36 times higher than for field galaxies. All five confirmed sub-mm galaxies in the HerBS-70 system have relatively short gas depletion times (80−500 Myr), indicating the onset of quenching for this protocluster core due to the depletion of gas. The dark matter halo mass of the HerBS-70 system is estimated around 5 × 1013 M⊙, with a projected current-day mass of 1015 M⊙, similar to the local Virgo and Coma clusters. These observations support the claim that DSFGs, in particular the ones with observed multiplicity, can trace cosmic overdensities.
Time-dependent AGN disc winds – I. X-ray irradiation
Authors: Dyda Sergei , Davis Shane W , Proga Daniel
Published: April 2024

We study active galactic nucleus (AGN) line-driven disc winds using time-dependent radiation hydrodynamics. The key criterion for determining wind launching is the coupling strength of the ultraviolet radiation field via the spectral lines of the gas. The strength of these lines in turn relies crucially on the gas ionization state, determined by the local X-ray intensity. We consider a suite of models where the central ionizing radiation is affected by scattering, absorption, and re-emission by the intervening gas. In a pure attenuation model, the disc launches an episodic wind, as previous studies have shown. Including scattering or re-emission tends to weaken the wind, lowering the mass flux and outflow velocity and, if sufficiently dominant, suppressing the outflow entirely. However, the exponential nature of radiative attenuation means that only a modest, factor of a few, increase in the absorption cross-section can overcome the wind suppression due to scattering and re-emission. We find mass outflow rates of ∼20 per cent or more of the assumed inflow rate through the disc, indicating that radiation-driven winds may significantly alter the structure of the accretion flow. The winds also supply a large, time-varying column of material above the nominal constant disc scale height, which will determine the geometry of reprocessed emission from the central source. Our results suggest the need for accurate photoionization modelling, radiation transport, and accretion disc physics, to study their effects on the AGN disc winds.
Viral SARS-CoV-2 Rebound Rates in Linked Commercial Pharmacy-Based Testing and Health Care Claims
Authors: Kelly Scott P , McEwen Lisa M , Isaksson Magnus , Murphy Sarah , White Simon , Levy Matthew E , McCrone John T , Levan Geraint , Santhanam Sharad , Baniecki Mary Lynn , Bramson Candace , Rubino Heather , Hendrick Vicky , Soares Holly , Hammond Jennifer , Luo Shishi
Published: April 2024

Background

Viral SARS-CoV-2 rebound (viral RNA rebound) is challenging to characterize in large cohorts due to the logistics of collecting frequent and regular diagnostic test results. Pharmacy-based testing data provide an opportunity to study the phenomenon in a large population, also enabling subgroup analyses. The current real-world evidence approach complements approaches focused on smaller, prospective study designs.

Methods

We linked real-time reverse transcription quantitative polymerase chain reaction test data from national pharmacy-based testing to health care claims data via tokenization to calculate the cumulative incidence of viral RNA rebound within 28 days following positive test results in nirmatrelvir/ritonavir (NMV-r)–treated and untreated individuals during the Omicron era (December 2021–November 2022) and prior to the Omicron era (October 2020–November 2021).

Results

Among 30 646 patients, the rate of viral RNA rebound was 3.5% (95% CI, 2.0%–5.7%) in NMV-r–treated infections as compared with 1.5% (95% CI, 1.3%–1.7%) in untreated infections during the Omicron era and 1.9% (95% CI, 1.7%–2.1%) prior to the Omicron era. Viral RNA rebound in patients who were vaccinated (n = 8151), high risk (n = 4411), or older (≥65 years, n = 4411) occurred at comparable rates to the overall cohort (range, 1.1%–4.8%). Viral rebounds to high RNA levels in NMV-r–treated infections occurred in 8% of viral rebounds as compared with 5% to 11% in untreated infections. Rates of hospitalization were comparable between patients with NMV-r–treated infections with viral RNA rebound (0%) and untreated patients with viral RNA rebound (0%–1.2%).

Conclusions

Our findings suggest viral RNA rebound is rare (< 5%), with rates that were consistent with those from the EPIC-HR trial (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients). Most occurrences of viral RNA rebound were associated with low viral RNA levels, and viral RNA rebound progression to severe disease was not observed.
Seigneurial predation in the late medieval feud
Authors: Sharp Tristan W
Published: April 2024

This article challenges the ‘from-lordship-to-government’ model of the grand narrative of European state formation through a reconceptualization of the late medieval German feud and lordship (1300–1500). It demonstrates how the predatory lordship of the feudal revolution persisted in late medieval imperial lands by centring on how modalities of extractive violence linked the lordly feud and lordship together in a system of seigneurial violence. It thus returns to Gadi Algazi’s controversial thesis that seigneurial lordship was a protection racket enabled by the omnipresent potential of the feud’s lordly violence. The author proposes that an overlooked body of evidence, damage registers (Schadensverzeichnisse), provides the evidence necessary for confirming and broadening Algazi’s insights. Through an archival collection of these documents, the author elucidates how this late medieval system of seigneurial violence was typified by a continuum of extractive violence from plundering to the levying of tribute and protection. In doing so, the author highlights how this system of seigneurial violence, lordship, and late medieval advances in governance held the potential to work together in far more complex ways than the ‘from-lordship-to-government’ narrative acknowledges.