bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADAD1 is required for normal translation of nuclear pore and transport protein transcripts in spermatids ofMus musculus
Authors: Potgieter Sarah , Eddy Christopher , Badrinath Aditi , Chukrallah Lauren , Lo Toby , Mohanty Gayatri , Visconti Pablo E , Snyder Elizabeth M 
Published: June 2023

AbstractADAD1 is a testis-specific RNA-binding protein expressed in post-meiotic spermatids whose loss leads to defective sperm and male infertility. However, the drivers of the Adad1 phenotype remain unclear. Morphological and functional analysis of Adad1 mutant sperm showed defective DNA compaction, abnormal head shaping, and reduced motility. Mutant testes demonstrated minimal transcriptome changes; however, ribosome association of many transcripts was reduced, suggesting ADAD1 may be required for their translational activation. Further, immunofluorescence of proteins encoded by select transcripts showed delayed protein accumulation. Additional analyses demonstrated impaired subcellular localization of multiple proteins, suggesting protein transport is also abnormal in Adad1 mutants. To clarify the mechanism giving rise to this, the manchette, a protein transport microtubule network, and the LINC (linker of nucleoskeleton and cytoskeleton) complex, which connects the manchette to the nuclear lamin, were assessed across spermatid development. Proteins of both displayed delayed translation and/or localization in mutant spermatids implicating ADAD1 in their regulation, even in the absence of altered ribosome association. Finally, ADAD1’s impact on the NPC (nuclear pore complex), a regulator of both the manchette and the LINC complex, was examined. Reduced ribosome association of NPC encoding transcripts and reduced NPC protein abundance along with abnormal localization in Adad1 mutants confirmed ADAD1's impact on translation is required for a NPC in post-meiotic germ cells. Together, these studies lead to a model whereby ADAD1’s influence on nuclear transport leads to deregulation of the LINC complex and the manchette, ultimately generating the range of physiological defects observed in the Adad1 phenotype.
O018 A virtual reality training platform for surgeons, anaesthetists, and obstetricians in low and middle-income countries
Authors: Bolton WS , Aruparayil NK , Please H , Patel R , Dalton J , Agery B , Mwachiro M , Ndizeye O , Daya L , Bains L , Mishra A , Jani P , Culmer PR , Gnanaraj J , Jayne DG , Dhanda J 
Published: June 2023

Abstract

Introduction
Many surgeons, anaesthetists, and obstetricians in low and middle-income countries (LMICs) lack access to training opportunities. The purpose of this study was to evaluate the feasibility of VR procedural training at scale for these specialties.

Methods
An online, free to participant, single-day event programme was designed to cover operative anatomy and procedural steps for Bellwether procedures including Laparotomy and Caesarean section, use of a novel gasless laparoscopic surgery device, administration of spinal anaesthetic and basic trauma principles. Demonstration was performed using fresh frozen cadavers and virtual presentations. Faculty comprised of an equal split between UK and LMIC surgeons from a range of countries virtually connected. The 4K live 360°VR broadcast was achieved via vMix virtual video switcher. vMix Call remote broadcast contributor links and additional angles via NDI IP system.

Results
A total of 236 unique live views were generated. Participants were from 43 countries (n=17 high income countries: n=26 LMICs). In addition, fifty cardboard headsets were transported to two sites for dissemination to local trainees and students: Nairobi, Kenya, and Delhi, India. The mean per-user engagement time for the group was 132 minutes. Nine LMICs had an average per country user engagement of &gt;140 minutes.

Conclusion
It is feasible to live stream surgical training videos in VR and achieve significant user engagement for participants from LMICs. This technology allowed resources and faculty in a HIC setting to collaborate in real-time with faculty input from LMIC via virtual reality, facilitating multi-directional learning.

Take-home message
Live virtual reality surgical training courses are feasible and can provide scalable learning environments, achieving significant engagement from surgeons, obstetricians and anaesthetists across the world, including several low and middle-income countries.
Cardiac lipid metabolism, mitochondrial function, and heart failure
Authors: Da Dalt Lorenzo , Cabodevilla Ainara G , Goldberg Ira J , Norata Giuseppe Danilo 
Published: June 2023

Abstract
A fine balance between uptake, storage, and the use of high energy fuels, like lipids, is crucial in the homeostasis of different metabolic tissues. Nowhere is this balance more important and more precarious than in the heart. This highly energy-demanding muscle normally oxidizes almost all the available substrates to generate energy, with fatty acids being the preferred source under physiological conditions.
In patients with cardiomyopathies and heart failure, changes in the main energetic substrate are observed; these hearts often prefer to utilize glucose rather than oxidizing fatty acids. An imbalance between uptake and oxidation of fatty acid can result in cellular lipid accumulation and cytotoxicity. In this review, we will focus on the sources and uptake pathways used to direct fatty acids to cardiomyocytes. We will then discuss the intracellular machinery used to either store or oxidize these lipids and explain how disruptions in homeostasis can lead to mitochondrial dysfunction and heart failure. Moreover, we will also discuss the role of cholesterol accumulation in cardiomyocytes. Our discussion will attempt to weave in vitro experiments and in vivo data from mice and humans and use several human diseases to illustrate metabolism gone haywire as a cause of or accomplice to cardiac dysfunction.
Lipocalin 10 is essential for protection against inflammation-triggered vascular leakage by activating LDL receptor-related protein 2-slingshot homologue 1 signalling pathway
Authors: Zhao Hongyan , Wang Peng , Wang Xiaohong , Du Wa , Yang Hui-Hui , Liu Yueying , Cui Shu-Nan , Huang Wei , Peng Tianqing , Chen Jing , Gao Chen , Wang Yigang , Sadayappan Sakthivel , Ma Chengen , Fan Yanbo , Wang Chunting , Fan Guo-Chang 
Published: June 2023

Abstract

Aims
Systemic inflammation occurs commonly during many human disease settings and increases vascular permeability, leading to organ failure, and lethal outcomes. Lipocalin 10 (Lcn10), a poorly characterized member of the lipocalin family, is remarkably altered in the cardiovascular system of human patients with inflammatory conditions. Nonetheless, whether Lcn10 regulates inflammation-induced endothelial permeability remains unknown.

Methods and results
Systemic inflammation models were induced using mice by injection of endotoxin lipopolysaccharide (LPS) or caecal ligation and puncture (CLP) surgery. We observed that the expression of Lcn10 was dynamically altered only in endothelial cells (ECs), but not in either fibroblasts or cardiomyocytes isolated from mouse hearts following the LPS challenge or CLP surgery. Using in vitro gain- and loss-of-function approaches and an in vivo global knockout mouse model, we discovered that Lcn10 negatively regulated endothelial permeability upon inflammatory stimuli. Loss of Lcn10 augmented vascular leakage, leading to severe organ damage and higher mortality following LPS challenge, compared to wild-type controls. By contrast, overexpression of Lcn10 in ECs displayed opposite effects. A mechanistic analysis revealed that both endogenous and exogenous elevation of Lcn10 in ECs could activate slingshot homologue 1 (Ssh1)-Cofilin signalling cascade, a key axis known to control actin filament dynamics. Accordingly, a reduced formation of stress fibre and increased generation of cortical actin band were exhibited in Lcn10-ECs, when compared to controls upon endotoxin insults. Furthermore, we identified that Lcn10 interacted with LDL receptor-related protein 2 (LRP2) in ECs, which acted as an upstream factor of the Ssh1-Confilin signalling. Finally, injection of recombinant Lcn10 protein into endotoxic mice showed therapeutic effects against inflammation-induced vascular leakage.

Conclusion
This study identifies Lcn10 as a novel regulator of EC function and illustrates a new link in the Lcn10-LRP2-Ssh1 axis to controlling endothelial barrier integrity. Our findings may provide novel strategies for the treatment of inflammation-related diseases.
Coronary microevaginations characterize culprit plaques and their inflammatory microenvironment in a subtype of acute coronary syndrome with intact fibrous cap: results from the prospective translational OPTICO-ACS study
Authors: Seppelt Claudio , Abdelwahed Youssef S , Meteva Denitsa , Nelles Gregor , Stähli Barbara E , Erbay Aslihan , Kränkel Nicolle , Sieronski Lara , Skurk Carsten , Haghikia Arash , Sinning David , Dreger Henryk , Knebel Fabian , Trippel Tobias D , Krisper Maximilian , Gerhardt Teresa , Rai Himanshu , Klotsche Jens , Joner Michael , Landmesser Ulf , Leistner David M 
Published: June 2023

Abstract

Aims
Coronary microevaginations (CMEs) represent an outward bulge of coronary plaques and have been introduced as a sign of adverse vascular remodelling following coronary device implantation. However, their role in atherosclerosis and plaque destabilization in the absence of coronary intervention is unknown. This study aimed to investigate CME as a novel feature of plaque vulnerability and to characterize its associated inflammatory cell–vessel–wall interactions.

Methods and results
A total of 557 patients from the translational OPTICO-ACS study programme underwent optical coherence tomography imaging of the culprit vessel and simultaneous immunophenotyping of the culprit lesion (CL). Two hundred and fifty-eight CLs had a ruptured fibrous cap (RFC) and one hundred had intact fibrous cap (IFC) acute coronary syndrome (ACS) as an underlying pathophysiology. CMEs were significantly more frequent in CL when compared with non-CL (25 vs. 4%, P &lt; 0.001) and were more frequently observed in lesions with IFC-ACS when compared with RFC-ACS (55.0 vs. 12.7%, P &lt; 0.001). CMEs were particularly prevalent in IFC-ACS-causing CLs independent of a coronary bifurcation (IFC-ICB) when compared with IFC-ACS with an association to a coronary bifurcation (IFC-ACB, 65.4 vs. 43.7%, P = 0.030). CME emerged as the strongest independent predictor of IFC-ICB (relative risk 3.36, 95% confidence interval 1.67–6.76, P = 0.001) by multivariable regression analysis. IFC-ICB demonstrated an enrichment of monocytes in both culprit blood analysis (culprit ratio: 1.1 ± 0.2 vs. 0.9 ± 0.2, P = 0.048) and aspirated culprit thrombi (326 ± 162 vs. 96 ± 87 cells/mm2, P = 0.017), while IFC-ACB confirmed the accumulation of CD4+ T cells, as recently described.

Conclusion
This study provides novel evidence for a pathophysiological involvement of CME in the development of IFC-ACS and provides first evidence for a distinct pathophysiological pathway for IFC-ICB, driven by CME-derived flow disturbances and inflammatory activation involving the innate immune system.

Trial registration
Registration of the study at clinicalTrials.gov (NCT03129503).
Cardiovascular risks of continuing vs. initiating NSAIDs after first-time myocardial infarction or heart failure: a nationwide cohort study
Authors: Schmidt Morten , Hallas Jesper , Ernst Martin Thomsen , Pottegård Anton 
Published: June 2023

Abstract

Aims
It is unknown whether the cardiovascular risks associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) shortly after first-time myocardial infarction (MI) or heart failure (HF) differ between patients continuing and initiating use.

Methods and results
Using nationwide health registries, we conducted a cohort study of all patients with first-time MI or HF during 1996–2018 (n = 273 682). NSAID users (n = 97 966) were categorized as continuing (17%) and initiating (83%) users according to prescription fillings &lt; 60 days before index diagnosis. The primary outcome was a composite of new MI, HF admission, and all-cause death. Follow-up started 30 days after the index discharge date. We used Cox regression to compute hazard ratios (HRs) with 95% confidence intervals (CIs) comparing NSAID users vs. non-users. The most commonly filled NSAIDs were ibuprofen (50%), diclofenac (20%), etodolac (8.5%), and naproxen (4.3%). The composite outcome HR of 1.25 (CI: 1.23–1.27) was driven by initiators (HR = 1.39, 1.36–1.41) and not continuing users (HR = 1.03, 1.00–1.07). The lack of association among continuing users was also observed for individual NSAIDs (ibuprofen and naproxen), except diclofenac (HR = 1.11, 95% CI: 1.05–1.18). Among initiators, the HR was 1.63 (CI: 1.57–1.69) for diclofenac, 1.31 (CI: 1.27–1.35) for ibuprofen, and 1.19 (CI: 1.08–1.31) for naproxen. The results were consistent for both MI and HF patients, the individual components of the composite outcome, and various sensitivity analyses.

Conclusion
NSAID initiators were more susceptible to adverse cardiovascular outcomes after first-time MI or HF than continuing users.
Coronary microcirculatory dysfunction can be assessed by positive dicrotic wave and amplitude index on resting distal coronary pressure waveform, a newly developed index
Authors: Fujimori Yoshiharu , Hashimoto Satoshi , Takahashi Miki , Hoshino Hirotada , Shimizu Kenji , Terasawa Yuya , Wakabayashi Tadamasa , Imai Taku 
Published: June 2023

Abstract

Aims
Some lesions have high resting distal coronary pressure/aortic pressure (Pd/Pa) despite low fractional flow reserve (FFR). This study aimed to assess microcirculatory dysfunction as a possible basal mechanism.

Methods and results
Patients were grouped into two according to coffee intake (caffeine 222 mg) before coronary angiography. Through an adenosine-induced Pd/Pa decrease, amplitude index was calculated by dividing the difference between the highest pressure after the inflection point and the minimal diastolic pressure by the pulse pressure on the Pd waveform. In 130 coronary lesions (caffeine group, n = 69; non-caffeine group, n = 61) from 113 patients, the amplitude index through the adenosine-induced Pd/Pa decrease in all lesions was 0.54 ± 0.11 at resting Pd/Pa and 0.44 ± 0.12 at FFR (P &lt; 0.0001). The positive dicrotic wave distribution on a maximal hyperaemia (FFRnicr)–resting Pd/Pa graph was analysed. In lesions with FFRnicr &lt;0.80 on the FFRnicr–resting Pd/Pa graph, the resting Pd/Pa was divided into three zones based on Pd/Pa values: high-remaining, intermediate, and low. The high-remaining zone had a higher amplitude index than the intermediate zone (0.60 ± 0.09 vs. 0.48 ± 0.12; P &lt; 0.005); the low zone lesions had no inflection point (no amplitude index). The high-remaining zone correlated with a larger positive dicrotic wave than the intermediate zone (94 vs. 30%; P &lt; 0.005). Most lesions in the high-remaining zone corresponded to the caffeine group.

Conclusion
In severe coronary stenosis, a high-remaining resting Pd/Pa with a high amplitude index or a positive dicrotic wave on the resting Pd waveform suggests microcirculatory dysfunction, such as insufficient arteriolar dilation reactive to myocardial ischaemia.

Registration
UMIN000046883.
Left ventricular functional recovery after atrial fibrillation catheter ablation in heart failure: a prediction model
Authors: Bergonti Marco , Ascione Ciro , Marcon Lorenzo , Pambrun Thomas , Della Rocca Domenico G , Ferrero Teba Gonzalez , Pannone Luigi , Kühne Michael , Compagnucci Paolo , Bonomi Alice , Gevaert Andreas B , Anselmino Matteo , Casella Michela , Krisai Philipp , Tondo Claudio , Rodríguez-Mañero Moises , Derval Nicolas , Chierchia Gian-Battista , de Asmundis Carlo , Heidbuchel Hein , Jaïs Pierre , Sarkozy Andrea 
Published: June 2023

Abstract

Aims
Management of patients with atrial fibrillation (AF) and concomitant heart failure (HF) remains complex. The Antwerp score, based on four parameters [QRS &gt;120 ms (2 points), known aetiology (2 points), paroxysmal AF (1 point), severe atrial dilation (1 point)] adequately estimated the probability of left ventricular ejection fraction (LVEF) recovery after AF ablation in a single-centre cohort. The present study aims to externally validate this prediction model in a large European multi-centre cohort.

Methods and results
A total of 605 patients (61.1 ± 9.4 years, 23.8% females, 79.8% with persistent AF) with HF and impaired LVEF (&lt;50%) undergoing AF ablation in 8 European centres were retrospectively identified. According to the LVEF changes at 12-month echocardiography, 427 (70%) patients fulfilled the ‘2021 Universal Definition of HF’ criteria for LVEF recovery and were defined as ‘responders’. External validation of the score yielded good discrimination and calibration {area under the curve 0.86 [95% confidence interval (CI) 0.82–0.89], P &lt; .001; Hosmer–Lemeshow P = .29}. Patients with a score &lt; 2 had a 93% probability of LVEF recovery as opposed to only 24% in patients with a score &gt; 3. Responders experienced more often positive ventricular remodelling [odds ratio (OR) 8.91, 95% CI 4.45–17.84, P &lt; .001], fewer HF hospitalizations (OR 0.09, 95% CI 0.05–0.18, P &lt; .001) and lower mortality (OR 0.11, 95% CI 0.04–0.31, P &lt; .001).

Conclusion
In this multi-centre study, a simple four-parameter score predicted LVEF recovery after AF ablation in patients with HF and discriminated clinical outcomes. These findings support the use of the Antwerp score to standardize shared decision-making regarding AF ablation referral in future clinical studies.
Evaluating power to detect recurrent selective sweeps under increasingly realistic evolutionary null models
Authors: Soni Vivak , Johri Parul , Jensen Jeffrey D 
Published: June 2023

Abstract
The detection of selective sweeps from population genomic data often relies on the premise that the beneficial mutations in question have fixed very near the sampling time. As it has been previously shown that the power to detect a selective sweep is strongly dependent on the time since fixation as well as the strength of selection, it is naturally the case that strong, recent sweeps leave the strongest signatures. However, the biological reality is that beneficial mutations enter populations at a rate, one that partially determines the mean wait time between sweep events and hence their age distribution. An important question thus remains about the power to detect recurrent selective sweeps when they are modeled by a realistic mutation rate and as part of a realistic distribution of fitness effects, as opposed to a single, recent, isolated event on a purely neutral background as is more commonly modeled. Here we use forward-in-time simulations to study the performance of commonly used sweep statistics, within the context of more realistic evolutionary baseline models incorporating purifying and background selection, population size change, and mutation and recombination rate heterogeneity. Results demonstrate the important interplay of these processes, necessitating caution when interpreting selection scans; specifically, false-positive rates are in excess of true﻿-positive across much of the evaluated parameter space, and selective sweeps are often undetectable unless the strength of selection is exceptionally strong.
Parental experiences and opinions regarding the management of acute otitis media in Finland—a comparative questionnaire between 2006 and 2019
Authors: Jokinen Sylvia , Ruohola Aino , Tähtinen Paula A 
Published: June 2023

Abstract

Background
Treatment guidelines for acute otitis media (AOM) have changed over the past 20 years. Watchful waiting is often recommended as an option for antibiotic treatment and the use of proper pain medication is emphasised.

Objective
To study parental experiences and opinions regarding the management of AOM and compare our findings with our previous questionnaire submitted in 2006.

Methods
We sent an online survey link through day-care centres and Facebook parental groups in Turku area. Children &lt;4 years of age attending day care were included in the analysis. We asked about the child’s history of AOM, parental opinions about AOM treatment, and antibiotic resistance. Results of 2019 were compared with those of 2006.

Results
Altogether 84% (320/381) and 83% (568/681) of children had had at least 1 episode of AOM in 2019 and 2006, respectively. In 2019, more children had been treated without antibiotics (30% vs. 13%, P &lt; 0.001) and fewer parents thought that antibiotics are necessary for the treatment of AOM (70% vs. 85%, P &lt; 0.001) compared with 2006. The use and knowledge of painkillers had increased over the past 13 years. Painkillers had been given at least once to 93% (296/320) of children in 2019 and 80% (441/552) of children in 2006 (P &lt; 0.001).

Conclusions
Today, more parents accept watchful waiting as a treatment option for AOM and give painkillers to their children, which indicates that the education about optimal management of AOM has reached parents.
Automated characterization of forest canopy vertical layering for predicting forest inventory attributes by layer using airborne LiDAR data
Authors: Penner Margaret , White Joanne C , Woods Murray E 
Published: June 2023

Abstract
Forest canopy vertical layering influences stand development and yield and is critical information for forest management planning and wood supply analysis. It is also relevant for other applications including habitat modelling, forest fuels management and assessing forest resilience. Forest inventories that use coincident airborne Light Detection and Ranging (LiDAR) data and field plots (i.e. area-based approach) to predict forest attributes generally do not consider the multi-layer canopy structure that may be found in many natural and managed forest stands. With airborne LiDAR, it is possible to separate single-layer and multi-layer stands. This information can be used to allocate predictions of forest attributes such as timber volume (m3 ha−1), by canopy layer. In this study, we used single-photon LiDAR data to automate the mapping of vertical stand layering in a temperate mixedwood forest with a variety of forest types and vertical complexities. We first predicted whether each 25 × 25 m grid cell had one or two canopy layers, and then partitioned inventory attributes (e.g. basal area (BA), gross total stem volume (GTV)) by canopy layer. We compared two methods for estimating attributes by layer at the stand level using nine independent validation stands. Overall agreement between the reference and predicted structure for the calibration plots was 74% (n = 266). At the grid-cell level, attributes were generally underestimated for the upper layer and overestimated for the lower layer. For the validation stands, the relative height of the lower layer was under-predicted compared to the reference data (46–52% versus 57%), while the proportion of BA and GTV in the lower layer were very similar to the reference values (17–19% versus 18% for BA and 12–15% versus 12% for GTV). Overall, the approach showed promise in distinguishing single- and two-layered stand conditions and partitioning estimates of inventory attributes such as BA and GTV by layer—both for grid cells and at the stand level. The inclusion of forest information by canopy layer enhances the utility of LiDAR-derived forest inventories for forest management in forest areas with complex, multi-layer stand conditions.