bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving outcomes of AF ablation by integrated personalized lifestyle interventions: rationale and design of the prevention to improve outcomes of PVI (POP) trial
Authors: Vermeer Jasper , Vinck Tineke , de Louw Bianca , Slingerland Stacey , van ’t Veer Marcel , Regis Marta , Jansen Jos-marien , van den Heuvel Edwin , Dekker Lukas 
Published: April 2023

AbstractProgression of atrial fibrillation (AF) and outcomes of ablation therapy are strongly affected by modifiable risk factors. Although previous studies show beneficial effects of modifying single risk factors, there is lack of evidence from randomized controlled trials on the effects of integrated AF lifestyle programmes. The POP trial is designed to evaluate the clinical outcomes of a dedicated nurse-led AF lifestyle outpatient clinic in patients with symptomatic AF. This study is a prospective, 1:1 randomized, single centre, investigator-initiated clinical trial in 150 patients with paroxysmal or persistent AF referred for a first pulmonary vein isolation (PVI). Prior to the ablation, patients in the intervention group receive a personalized risk factor treatment programme in a specialized, protocolized, nurse-led outpatient clinic. Patient education and durable lifestyle management is promoted with an e-health platform. Patients in the control group receive standard care by cardiologists before ablation. The primary endpoint is the number of hospitalizations for re-ablation and cardioversion, with a follow-up of 12 months after ablation. Secondary endpoints include mortality, number of acute ischemic events, stroke or hospitalizations for heart failure, quality of life, number of ablations cancelled because of symptom reduction, and ablation success rate at 12 months. Determinants of patient and staff experience are explored and a cost-effectiveness analysis is included. The POP trial will help ascertain the efficacy and cost-effectiveness of an integrated technology-supported lifestyle therapy in patients with symptomatic AF. The trial is funded by the Netherlands Organisation for Health Research and Development [10070012010001]. Home sleep apnoea testing devices were provided by Itamar Medical, Ltd.ClinicalTrials.gov Identifier NCT05148338.
Graphical abstract

AF atrial fibrillation, OSA obstructive sleep apnoea, PFA pulsed field ablation, PVI pulmonary vein isolation.
Biomarkers for parkinsonian disorders in CNS-originating EVs: promise and challenges
Authors: Dutta Suman , Hornung Simon , Taha Hash Brown , Bitan Gal 
Published: April 2023

AbstractExtracellular vesicles (EVs), including exosomes, microvesicles, and oncosomes, are nano-sized particles enclosed by a lipid bilayer. EVs are released by virtually all eukaryotic cells and have been shown to contribute to intercellular communication by transporting proteins, lipids, and nucleic acids. In the context of neurodegenerative diseases, EVs may carry toxic, misfolded forms of amyloidogenic proteins and facilitate their spread to recipient cells in the central nervous system (CNS). CNS-originating EVs can cross the blood–brain barrier into the bloodstream and may be found in other body fluids, including saliva, tears, and urine. EVs originating in the CNS represent an attractive source of biomarkers for neurodegenerative diseases, because they contain cell- and cell state-specific biological materials. In recent years, multiple papers have reported the use of this strategy for identification and quantitation of biomarkers for neurodegenerative diseases, including Parkinson’s disease and atypical parkinsonian disorders. However, certain technical issues have yet to be standardized, such as the best surface markers for isolation of cell type-specific EVs and validating the cellular origin of the EVs. Here, we review recent research using CNS-originating EVs for biomarker studies, primarily in parkinsonian disorders, highlight technical challenges, and propose strategies for overcoming them.
Corneal confocal microscopy identifies corneal nerve loss and increased Langerhans cells in presymptomatic carriers and patients with hereditary transthyretin amyloidosis
Authors: Thimm Andreas , Carpinteiro Alexander , Oubari Sara , Papathanasiou Maria , Kessler Lukas , Rischpler Christoph , Malik Rayaz Ahmed , Herrmann Ken , Reinhardt Hans Christian , Rassaf Tienush , Kleinschnitz Christoph , Hagenacker Tim , Stettner Mark 
Published: April 2023

Abstract
Background
Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a rare, but life-threatening protein misfolding disorder due to TTR gene mutations. Cardiomyopathy (ATTRv-CM) and polyneuropathy (ATTRv-PN) with early small nerve fibre involvement are the most common manifestations. Timely diagnosis and treatment initiation are key to limiting progression of disease. Corneal confocal microscopy (CCM) is a non-invasive method to quantify corneal small nerve fibres and immune cell infiltrates in vivo.

Methods
This cross-sectional study investigated the utility of CCM in 20 patients with ATTRv amyloidosis (ATTRv-CM, n = 6; ATTRv-PN, n = 14) and presymptomatic carriers (n = 5) compared to 20 age- and sex-matched healthy controls. Corneal nerve fibre density, corneal nerve fibre length, corneal nerve branch density, and cell infiltrates were assessed.

Results
Corneal nerve fibre density and nerve fibre length were significantly lower in patients with ATTRv amyloidosis compared to healthy controls regardless of the clinical phenotype (ATTRv-CM, ATTRv-PN) and corneal nerve fibre density was significantly lower in presymptomatic carriers. Immune cell infiltrates were only evident in patients with ATTRv amyloidosis, which correlated with reduced corneal nerve fibre density.

Conclusions
CCM identifies small nerve fibre damage in presymptomatic carriers and symptomatic patients with ATTRv amyloidosis and may serve as a predictive surrogate marker to identify individuals at risk of developing symptomatic amyloidosis. Furthermore, increased corneal cell infiltration suggests an immune-mediated mechanism in the pathogenesis of amyloid neuropathy.
Concurrent metaboreflex activation increases chronotropic and ventilatory responses to passive leg movement without sex-related differences
Authors: Laginestra Fabio Giuseppe , Favaretto Thomas , Giuriato Gaia , Martignon Camilla , Barbi Chiara , Pedrinolla Anna , Cavicchia Alessandro , Venturelli Massimo 
Published: April 2023

AbstractPrevious studies in animal models showed that exercise-induced metabolites accumulation may sensitize the mechanoreflex-induced response. The aim of this study was to assess whether the magnitude of the central hemodynamic and ventilatory adjustments evoked by isolated stimulation of the mechanoreceptors in humans are influenced by the prior accumulation of metabolic byproducts in the muscle. 10 males and 10 females performed two exercise bouts consisting of 5-min of intermittent isometric knee-extensions performed 10% above the previously determined critical force. Post-exercise, the subjects recovered for 5 min either with a suprasystolic circulatory occlusion applied to the exercised quadriceps (PECO) or under freely-perfused conditions (CON). Afterwards, 1-min of continuous passive leg movement was performed. Central hemodynamics, pulmonary data, and electromyography from exercising/passively-moved leg were recorded throughout the trial. Root mean square of successive differences (RMSSD, index of vagal tone) was also calculated. Δpeak responses of heart rate (ΔHR) and ventilation ($$\Delta \dot{V}_{{\text{E}}}$$

Δ

V
˙

E

) to passive leg movement were higher in PECO compared to CON (ΔHR: 6 ± 5 vs 2 ± 4 bpm, p = 0.01; 3.9 ± 3.4 vs 1.9 ± 1.7 L min−1, p = 0.02). Δpeak of mean arterial pressure (ΔMAP) was significantly different between conditions (5 ± 3 vs  − 3 ± 3 mmHg, p < 0.01). Changes in RMSSD with passive leg movement were different between PECO and CON (p < 0.01), with a decrease only in the former (39 ± 18 to 32 ± 15 ms, p = 0.04). No difference was found in all the other measured variables between conditions (p > 0.05). These findings suggest that mechanoreflex-mediated increases in HR and $$\dot{V}_{{\text{E}}}$$

V
˙

E

are sensitized by metabolites accumulation. These responses were not influenced by biological sex.
Apomixis: oh, what a tangled web we have!
Authors: Niccolò Terzaroli , Anderson Aaron W. , Emidio Albertini 
Published: April 2023

Abstract
Main conclusion
Apomixis is a complex evolutionary trait with many possible origins. Here we discuss various clues and causes, ultimately proposing a model harmonizing the three working hypotheses on the topic.

Abstract
Asexual reproduction through seeds, i.e., apomixis, is the holy grail of plant biology. Its implementation in modern breeding could be a game-changer for agriculture. It has the potential to generate clonal crops and maintain valuable complex genotypes and their associated heterotic traits without inbreeding depression. The genetic basis and origins of apomixis are still unclear. There are three central hypothesis for the development of apomixis that could be: i) a deviation from the sexual developmental program caused by an asynchronous development, ii) environmentally triggered through epigenetic regulations (a polyphenism of sex), iii) relying on one or more genes/alleles. Because of the ever-increasing complexity of the topic, the path toward a detailed understanding of the mechanisms underlying apomixis remains unclear. Here, we discuss the most recent advances in the evolution perspective of this multifaceted trait. We incorporated our understanding of the effect of endogenous effectors, such as small RNAs, epigenetic regulation, hormonal pathways, protein turnover, and cell wall modification in response to an upside stress. This can be either endogenous (hybridization or polyploidization) or exogenous environmental stress, mainly due to oxidative stress and the corresponding ROS (Reacting Oxygen Species) effectors. Finally, we graphically represented this tangled web.
Atypical meningiomas with an immunohistochemical profile consistent with hypermetabolic or proliferative molecular groups show high mitotic index, chromosomal instability, and higher recurrence risk
Authors: Barresi Valeria , Ammendola Serena , Simbolo Michele , Pedron Serena , Caffo Maria , Scarpa Aldo 
Published: April 2023

AbstractThe use of adjuvant radiotherapy is controversial for atypical meningiomas undergoing gross total resection. It has recently been proposed that meningiomas may be classified into four molecular groups (MG): immunogenic (MG1), benign NF2-wildtype (MG2), hypermetabolic (MG3), and proliferative (MG4). The two latter have the worst prognosis, and it has been suggested that they can be identified using ACADL and MCM2 immunostainings. We studied 55 primary atypical meningiomas, treated with gross total resection and no adjuvant therapies, to assess whether ACADL and MCM2 immuno-expression may identify patients at higher recurrence risk, thus requiring adjuvant treatments. Twelve cases resulted ACADL-/MCM2-, 9 ACADL + /MCM2-, 17 ACADL + /MCM2 + , and 17 ACADL-/MCM2 + . MCM2 + meningiomas displayed more frequent atypical features (prominent nucleoli, small cells with high nuclear-to-cytoplasmic ratio) and CDKN2A hemizygous deletion (HeDe) (P = 0.011). The immunoexpression of ACADL and/or MCM2 was significantly associated with higher mitotic index, 1p and 18q deletions, increased recurrence rate (P = 0.0006), and shorter recurrence-free survival (RFS) (P = 0.032). At multivariate analysis, carried out including ACADL/MCM2 immuno-expression, mitotic index, and CDKN2A HeDe as covariates, this latter resulted a significant and independent prognosticator of shorter RFS (P = 0.0003).
Development of myelin in fetal and postnatal neocortex of the pig, the European wild boar Sus scrofa
Authors: Sobierajski Eric , Lauer German , Czubay Katrin , Grabietz Hannah , Beemelmans Christa , Beemelmans Christoph , Meyer Gundela , Wahle Petra 
Published: April 2023

AbstractMyelination of the neocortex of altricial species is mostly a postnatal event, and the appearance of myelin has been associated with the end of the critical period for ocular dominance plasticity in rodent visual cortex. Due to their precocality, ungulates may tell a different story. Here, we analyzed the development of PDGFRα positive oligodendrocyte precursor cells and expression of myelin proteins in the laminar compartments of fetal and postnatal porcine cortex from E45 onwards. Precursor cell density initially increased and then decreased but remained present at P90. MAG and MBP staining were detectable at E70 in subventricular zone and deep white matter, ascending into gyral white matter at E85, and into the gray matter and marginal zone at E100 (birth in pig at E114). Protein blots confirmed the declining expression of PDGFRα from E65 onwards, and the increase of MBP and MAG expression from E80 onwards. Somatosensory input elicited by spontaneous activity is considered important for the formation of the body representation. Indeed, PDGFRα, MBP and MAG expression started earlier in somatosensory than in visual cortex. Taken together, myelination proceeded in white and gray matter and marginal zone of pig cortex before birth with an areal-specific time course, and an almost mature pattern was present at P5 in visual cortex.
Rituximab-associated hypogammaglobulinemia in children with idiopathic nephrotic syndrome: results of an ESPN survey
Authors: Zurowska Aleksandra , Drozynska-Duklas Magdalena , Topaloglu Rezan , Bouts Antonia , Boyer Olivia , Shenoy Mohan , Vivarelli Marina ,   on behalf of ESPN Glomerulonephritis Working Group, Alpay H. , Andersen R. , Ariceta G. , Atmış B. , Bayrakçı U. S. , Esrea B. , Baudouin V. , Bervina N. , Benetti E. , Berard E. , Bjerre A. , Christian M. , Couderc A. , Dehoorne J. , Deschenes G. , Dossier C. , Düşünsel R. , Ekinci Z. , Emma F. , Espinoza L. , Gianviti A. , Herrero Goñi M. , Guido G. , Ghio L. , Groothoff J. , Hacıhamdioğlu D. Ö. , Espino Hernández M. , Jankauskiene A. , Kagan M. , Kemper M. , Kovacevic M. , Kohl S. , Kramar R. T. , López-González M. , Aris A. M. , Maringhini S. , Marlais M. , Melgosa M. , Mitsioni A. , Montini G. , Moczulska A. , Murer L. , Obukhova V. , Oh J. , Ortega P. , Özçakar Z. B. , Ulinski T. , Pasini A. , Papalia T. , Paunova S. , Pena A. , Pecoraro C. , Petrosyan E. , Peruzzi L. , Printza N. , Prikhodina L. , Pietrement C. , Rittig S. , Rodrigo D. , Savenkova N. , Saraga M. , Sever F. L. , Schreuder M. , Szczepanska M. , Tasic V. , Tonshoff B. , Tullus K. , Vara J. , Vande Walle J. , Volokhina E. , Zieg J. , Waters A. , Weber L. T. , Webbe N. , Wasiak M. 
Published: April 2023

Abstract
Background
There is paucity of information on rituximab-associated hypogammaglobulinemia (HGG) and its potential infectious consequences in children treated for idiopathic nephrotic syndrome (INS).

Methods
A survey was distributed by the European Society Pediatric Nephrology to its members. It addressed the screening and management practices of pediatric nephrology units for recognizing and treating RTX-associated HGG and its morbidity and mortality. Eighty-four centers which had treated an overall 1328 INS children with RTX responded.

Results
The majority of centers administered several courses of RTX and continued concomitant immunosuppressive therapy. Sixty-five percent of centers routinely screened children for HGG prior to RTX infusion, 59% during, and 52% following RTX treatment. Forty-seven percent had observed HGG prior to RTX administration, 61% during and 47% >9 months following treatment in 121, 210, and 128 subjects respectively. Thirty-three severe infections were reported among the cohort of 1328 RTX-treated subjects, of whom 3 children died. HGG had been recognized in 30/33 (80%) of them.

Conclusions
HGG in steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) children is probably multifactorial and can be observed prior to RTX administration in children with SDNS/FRNS. Persistent HGG lasting >9 months from RTX infusion is not uncommon and may increase the risk of severe infections in this cohort. We advocate for the obligatory screening for HGG in children with SDNS/FRNS prior to, during, and following RTX treatment. Further research is necessary to identify risk factors for developing both HGG and severe infections before recommendations are made for its optimal management.

Graphical abstract
A reactive path relinking algorithm for solving the bi-objective p-Median and p-Dispersion problem
Authors: Lozano-Osorio I. , Sánchez-Oro J. , López-Sánchez A. D. , Duarte A. 
Published: April 2023

AbstractThis paper deals with an interesting facility location problem known as the bi-objective p-Median and p-Dispersion problem (BpMD problem). The BpMD problem seeks to locate p facilities to service a set of n demand points, and the goal is to minimize the total distance between facilities and demand points and, simultaneously, maximize the minimum distance between all pairs of hosted facilities. The problem is addressed with a novel path relinking approach, called reactive path relinking, which hybridizes two of the most extended path relinking variants: interior path relinking and exterior path relinking. Additionally, the proposal is adapted to a multi-objective perspective for finding a good approximation of the Pareto front. Computational results prove the superiority of the proposed algorithm over the best procedures found in the literature.
Locating the propagation source in complex networks with observers-based similarity measures and direction-induced search
Authors: Yang Fan , Li Chungui , Peng Yong , Liu Jingxian , Yao Yabing , Wen Jiayan , Yang Shuhong 
Published: April 2023

AbstractLocating the propagation source is one of the most important strategies to control the harmful diffusion process on complex networks. Most existing methods only consider the infection time information of the observers, but the diffusion direction information of the observers is ignored, which is helpful to locate the source. In this paper, we consider both of the diffusion direction information and the infection time information to locate the source. We introduce a relaxed direction-induced search (DIS) to utilize the diffusion direction information of the observers to approximate the actual diffusion tree on a network. Based on the relaxed DIS, we further utilize the infection time information of the observers to define two kinds of observers-based similarity measures, including the Infection Time Similarity and the Infection Time Order Similarity. With the two kinds of similarity measures and the relaxed DIS, a novel source locating method is proposed. We validate the performance of the proposed method on a series of synthetic and real networks. The experimental results show that the proposed method is feasible and effective in accurately locating the propagation source.
Growth pattern of lumbar maturity stage at L1 to L5 during adolescent growth spurt
Authors: Tsutsui Toshiharu , Iizuka Satoshi , Takei Seira , Sakamaki Wataru , Maemichi Toshihiro , Torii Suguru 
Published: April 2023

Abstract
Purpose
This study aimed to clarify the order of the lumbar maturity stage, each at L1 to L5, and the relationships between age at peak height velocity (APHV) and the lumbar maturity stage.

Methods
A total of 120 male first-grade junior high school soccer players were enrolled and followed for two years, and measurements were performed five times (T1 to T5). The lumbar maturity stage was assessed according to the degree of lesion of the epiphyseal from L1 to L5 using magnetic resonance imaging and classified into three stages: cartilaginous stage, apophyseal stage, and epiphyseal stage. The relationships between T1 and T5 temporal changes and developmental stages divided by 0.5 year increments based on APHV and the lumbar maturity stage at L1 to L5 were examined. For the apophyseal stage, developmental age calculated based on the difference between APHV and chronological age between each lumbar vertebra was compared.

Results
We found that part of the cartilaginous stages decreased as time progressed, while that of the apophyseal and epiphyseal stages increased at L1 to L5 (chi-square test, p < 0.01). L5 matured earlier with the apophyseal stage than L1 to L4 (p < 0.05). The lumbar maturity stage was attained toward L1 from L5, comparing different lumbar levels.

Conclusion
The lumbar maturity stage progresses from L5 toward L1, and the apophyseal and epiphyseal stages would replace the cartilaginous stage at approximately 14 years of age or after APHV.
Use of monofilament sutures and triclosan coating to protect against surgical site infections in spinal surgery: a laboratory-based study
Authors: Fawi H. M. T. , Papastergiou P. , Khan F. , Hart A. , Coleman N. P. 
Published: April 2023

Abstract
Purpose
We investigated bacterial propagation through multifilament, monofilament sutures and whether sutures coated with triclosan would exhibit a different phenomenon.

Methods
One centimetre (cm) wide trenches were cut in the middle of Columbia blood Agar plates. We tested a 6 cm length of two Triclosan-coated (PDS plus®, Vicryl plus®) and two uncoated (PDS ®, Vicryl ®) sutures. Each suture was inoculated with a bacterial suspension containing methicillin-sensitive Staphylococcus aureus (MSSA), Escherichia coli (E. coli), Staphylococcus epidermidis, methicillin-resistant Staphylococcus aureus (MRSA) at one end of each suture. The plates were incubated at 36C for 48 h, followed by room temperature for a further 5 days. We established bacterial propagation by observing for any bacterial growth on the Agar on the opposite side of the trench.

Results
Bacterial propagation was observed on the opposite side of the trench with both suture types, monofilament PDS and multifilament Vicryl, when tested with the motile bacterium (E. coli). Propagation was not observed on the other side of the trench with the monofilament PDS suture following incubation with MSSA and S. epidermidis, and in 66% of MRSA. With multifilament suture Vicryl, propagation was observed on the other side of the trench in 90% (MSSA), 80% (S. epidermidis), and 100% (MRSA) of plates tested. No bacterial propagation was observed in any of the triclosan-coated sutures (monofilament or multifilament).

Conclusions
Monofilament sutures are associated in vitro with less bacterial propagation along their course when compared to multifilament sutures. Inhibition in both sutures can be further enhanced with a triclosan coating.
An improved microfluidic device to enhance the enrichment factors in liquid phase microextraction: application to the simultaneous extraction of polar and non-polar acids in biological samples
Authors: Martín Alejandro , Fernández-Torres Rut , Bello-López Miguel Ángel , Ramos-Payán María 
Published: April 2023

AbstractA new microfluidic device to enhance the enrichment factor in miniaturized systems is proposed. The microfluidic system was design for liquid phase microextractions, and it was applied to the simultaneous extraction of acidic compounds of a wide range of polarity (0.5 < log P < 3). The device operated under stagnant acceptor phase conditions and all the operational parameters involved were optimized. Tributyl phosphate was found to be a new highly efficient supported liquid membrane to simultaneously extract analytes of very different polarities. The optimal donor and acceptor phase were pH 2 and pH 13, respectively. The donor flow rate and the extraction time were investigated simultaneously, offering great versatility with high enrichment factors (EFs). Limits of quantitation were within 0.02 and 0.09 µg mL−1 for all compounds at 10 µL min−1 as donor flow rate and 20-min extractions, offering EFs between 11 and 18 with only 200-µL sample volume consumption. The method was successfully applied to human urine samples, observing recoveries between 47 and 90% for all compounds. This new proposed microfluidic system increases the wide range of applications, especially when the analytes are present in lower concentrations in the sample.
Graphical Abstract