bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose intensification strategy influences infliximab pharmacokinetics but not clinical response after the same number of doses
Authors: Srinivasan Ashish , De Cruz Peter , Sam Melissa , Toong Catherine , van Langenberg Daniel R. 
Published: January 2023

AbstractBackgroundThe optimal infliximab dose intensification strategy to address secondary loss of response (LOR) remains unclear. This study aimed to compare clinical and pharmacokinetic outcomes following (i) upfront infliximab re‐induction with (ii) ongoing 6‐weekly dose interval shortening (DIS), after the same number of doses.MethodsA prospective parallel cohort study of inflammatory bowel disease patients who required infliximab dose intensification for secondary LOR using (i) re‐induction (i.e., repeat 5 mg/kg 0, 2, 6‐week dosing) followed by 8‐weekly maintenance or (ii) 6‐weekly 5 mg/kg DIS was undertaken. Week 32 clinical response was the primary outcome, with secondary evaluation of infliximab pharmacokinetics and predictors of response.ResultsOf 104 patients, 54 underwent re‐induction, and 50 underwent 6‐weekly DIS; 43 per cohort had clinically active disease, with comparable baseline infliximab levels (2.03 vs 2.02 ug/mL, P = 0.83). Clinical response was similar across re‐induction and DIS cohorts at weeks 12 (69.8 vs 65.1%) and 32 (53.5 vs 62.8%, each P > 0.50); however, both strategies demonstrated distinct pharmacokinetic profiles at weeks 6 (18.45 vs 5.36 ug/mL, P < 0.01), 12 (8.94 vs 5.96 ug/mL, P = 0.02) and 30 (3.89 vs 6.35 ug/mL, P = .0.02). In multivariable analyses, objectively verified active disease at baseline (OR 12.92, 95% CI [1.84–90.84], P = 0.01), subtherapeutic week 6 infliximab levels (OR 0.12, 95% CI [0.01, 0.99], P = 0.049) and week 12 clinical response (OR 5.44, 95% CI [1.20–19.97], P = 0.04) were associated with week 32 response, as were week 2 infliximab levels (OR 1.34, 95% CI [1.02–1.47], P = 0.04) following re‐induction. Following re‐induction, week 2 infliximab levels <15.6 ug/mL (AUROC 0.76, 95% CI [0.54–0.99], P < 0.05) predicted nonresponse at week 32.ConclusionDose intensification strategy impacted immediate and sustained infliximab levels but not clinical response. Upfront intensification was associated with short‐term pharmacokinetic advantages, including predictors of response, that diminished with time. Hence, when applying upfront dose intensification, clinicians should consider continuing intensified dosing to sustain early pharmacokinetic advantages based on predictors of (non)response.
A comprehensive anatomical network analysis of human brain topology
Authors: Schuurman Tim , Bruner Emiliano 
Published: January 2023

AbstractA network approach to the macroscopic anatomy of the human brain can be used to model physical interactions among regions in order to study their topological properties, as well as the topological properties of the overall system. Here, a comprehensive model of human brain topology is presented, based on traditional macroanatomical divisions of the whole brain, which includes its subcortical regions. The aim was to localise anatomical elements that are essential for the geometric balance of the brain, as to identify underlying phenotypic patterns of spatial arrangement and understand how these patterns may influence brain morphology in ontogeny and phylogeny. The model revealed that the parahippocampal gyrus, the anterior lobe of the cerebellum and the ventral portion of the midbrain are subjected to major topological constraints that are likely to limit or channel their morphological evolution. The present model suggests that the brain can be divided into a superior and an inferior morphological block, linked with extrinsic topological constraints imposed by the surrounding braincase. This information should be considered duly both in ontogenetic and phylogenetic studies of primate neuroanatomy.
Treat yourself: Food delivery apps and the interplay between justification for use and food well‐being
Authors: Capito Sabrina , Pergelova Albena 
Published: January 2023

AbstractThis study examines the relationship between justification for use and well‐being in respect to mobile food delivery apps (FDA). Adopting an interpretivist qualitative approach, the study offers contributions to the FDA and food well‐being literature by uncovering four groups of licensing effects that consumers use in justifying FDA use. Those licensing effects can have either positive or negative influence on consumers' well‐being depending on the degree to which consumers engage in self‐regulation, awareness, and conscious managing of their relationship with food. The study also unravels the importance of dealing with the tensions between FDA use and well‐being by shedding light on feelings of guilt and financial anxiety related to FDA use.
Going home: Clinician perspectives on decision‐making in paediatric home mechanical ventilation
Authors: Jeffreys Juliette , Rahman Mayukh , Vears Danya , Massie John 
Published: January 2023

AimDespite a recent increase in the use of ventilators in the home setting for children with chronic respiratory failure, there is currently no unified approach for clinical decision‐making for children requiring long‐term mechanical ventilation. The purpose of this study is to understand the clinician's perspective on decision‐making around home ventilation for children, and how home‐based care contributes to successful outcomes in this population.MethodsWe recruited physicians and home ventilation nurses with at least 2 years' experience working in an Australian paediatric tertiary home ventilation service using professional networks and snowball sampling. Semi‐structured interviews were conducted by two researchers between February 2019 and June 2020. Interviews were audio‐recorded, transcribed, and analysed using inductive content analysis.ResultsTwenty‐five individuals participated (17 physicians and 8 home ventilation nurses). Participants viewed themselves as impartial medical advocates in the decision‐making process, believing the decision to initiate or cease ventilation belonged to the child's family. While participants held the child's quality of life as the cornerstone of decision‐making, quality of life was subjective and family specific.ConclusionThese findings provide insight into how clinicians working with children with chronic respiratory insufficiency approach the decision to introduce home‐based ventilation. By understanding their role, strategies can be developed to assist them, leading to better outcomes for patients and families. Further research is needed to compare the perspectives of clinicians with the experience of ventilator‐assisted children and families in Australia.
Genomic diversity and differentiation between island and mainland populations of white‐tailed eagles (Haliaeetus albicilla)
Authors: Hansen Charles Christian Riis , Láruson Áki Jarl , Rasmussen Jacob Agerbo , Ballesteros Jesus Adrian Chimal , Sinding Mikkel‐Holger S. , Hallgrimsson Gunnar T. , von Schmalensee Menja , Stefansson Robert A. , Skarphédinsson Kristinn Haukur , Labansen Aili Lage , Leivits Madis , Sonne Christian , Dietz Rune , Skelmose Kim , Boertmann David , Eulaers Igor , Martin Michael D. , Helgason Agnar S. , Gilbert M. Thomas P. , Pálsson Snæbjörn 
Published: January 2023

AbstractDivergence in the face of high dispersal capabilities is a documented but poorly understood phenomenon. The white‐tailed eagle (Haliaeetus albicilla) has a large geographic dispersal capability and should theoretically be able to maintain genetic homogeneity across its dispersal range. However, following analysis of the genomic variation of white‐tailed eagles, from both historical and contemporary samples, clear signatures of ancient biogeographic substructure across Europe and the North‐East Atlantic is observed. The greatest genomic differentiation was observed between island (Greenland and Iceland) and mainland (Denmark, Norway and Estonia) populations. The two island populations share a common ancestry from a single mainland population, distinct from the other sampled mainland populations, and despite the potential for high connectivity between Iceland and Greenland they are well separated from each other and are characterized by inbreeding and little variation. Temporal differences also highlight a pattern of regional populations persisting despite the potential for admixture. All sampled populations generally showed a decline in effective population size over time, which may have been shaped by four historical events: (1) Isolation of refugia during the last glacial period 110–115,000 years ago, (2) population divergence following the colonization of the deglaciated areas ~10,000 years ago, (3) human population expansion, which led to the settlement in Iceland ~1100 years ago, and (4) human persecution and exposure to toxic pollutants during the last two centuries.
Characterizing zebra crossing zones using LiDAR data
Authors: Esmorís Alberto M. , Vilariño David L. , Arango David F. , Varela‐García Francisco‐Alberto , Cabaleiro José C. , Rivera Francisco F. 
Published: January 2023

AbstractLight detection and ranging (LiDAR) scanning in urban environments leads to accurate and dense three‐dimensional point clouds where the different elements in the scene can be precisely characterized. In this paper, two LiDAR‐based algorithms that complement each other are proposed. The first one is a novel profiling method robust to noise and obstacles. It accurately characterizes the curvature, the slope, the height of the sidewalks, obstacles, and defects such as potholes. It was effective for 48 of 49 detected zebra crossings, even in the presence of pedestrians or vehicles in the crossing zone. The second one is a detailed quantitative summary of the state of the zebra crossing. It contains information about the location, the geometry, and the road marking. Coarse grain statistics are more prone to obstacle‐related errors and are only fully reliable for 18 zebra crossings free from significant obstacles. However, all the anomalous statistics can be analyzed by looking at the associated profiles. The results can help in the maintenance of urban roads. More specifically, they can be used to improve the quality and safety of pedestrian routes.
Suppression of citrus canker disease mediated by flagellin perception
Authors: Andrade Maxuel de Oliveira , da Silva Jaqueline Cristina , Soprano Adriana Santos , Shimo Hugo Massayoshi , Leme Adriana Franco Paes , Benedetti Celso Eduardo 
Published: January 2023

AbstractCitrus cancer, caused by strains of Xanthomonas citri (Xc) and Xanthomonas aurantifolii (Xa), is one of the most economically important citrus diseases. Although our understanding of the molecular mechanisms underlying citrus canker development has advanced remarkably in recent years, exactly how citrus plants fight against these pathogens remains largely unclear. Using a Xa pathotype C strain that infects Mexican lime only and sweet oranges as a pathosystem to study the immune response triggered by this bacterium in these hosts, we herein report that the Xa flagellin C protein (XaFliC) acts as a potent defence elicitor in sweet oranges. Just as Xa blocked canker formation when coinfiltrated with Xc in sweet orange leaves, two polymorphic XaFliC peptides designated flgIII‐20 and flgIII‐27, not related to flg22 or flgII‐28 but found in many Xanthomonas species, were sufficient to protect sweet orange plants from Xc infection. Accordingly, ectopic expression of XaFliC in a Xc FliC‐defective mutant completely abolished the ability of this mutant to grow and cause canker in sweet orange but not Mexican lime plants. Because XaFliC and flgIII‐27 also specifically induced the expression of several defence‐related genes, our data suggest that XaFliC acts as a main immune response determinant in sweet orange plants.
Effect of orodispersible hyaluronic acid film on palatal mucosa wound healing
Authors: Lee Jeong Hyun , Lee Ko Eun , Kang Sang Wook , Park Seung Hwan , Chae Yong Kwon , Lee Myoung‐Han , Kweon Dong‐Keun , Choi Sung Chul , Nam Ok Hyung 
Published: January 2023

AbstractObjectiveThe objective of the study was to evaluate the healing effect of hyaluronic acid films on palatal wounds.Materials and MethodsAfter making 5‐mm diameter palatal wounds, 72 rats were randomly assigned to three groups: control, hyaluronic acid gel, and hyaluronic acid film. The animals were sacrificed at 3, 7, and 21 days after the experiment. Clinical, histological, and RT‐PCR analyses were performed. Human ex vivo oral mucosa models were used. Histological analysis and pan‐cytokeratin staining were performed at 5 days after wound creation.ResultsIn rat model, both gels and films showed favorable healing on Days 3 and 7 compared with healing in the control (p < 0.05). Film showed remarkable VEGF and α‐SMA expression than did the others (p < 0.05). Immunohistochemical analysis showed that film exhibited significantly lower CD68 and greater α‐SMA and vimentin expression levels than those in the others (p < 0.05). In human model, re‐epithelialization rate of film group was significantly higher than that of the others. Complete epithelial regeneration was confirmed only in film group using pan‐cytokeratin staining.ConclusionsWithin the limits of this study, hyaluronic acid film outperformed gels in terms of palatal wound healing in both models.
Spinal cord stimulation and return to work of patients with failed back surgery syndrome
Authors: Dauriac‐Le Masson Valérie , Gatt Marie‐Thérèse , Chekroun Corinne , Turak Baris , Djian Marie Christine 
Published: January 2023

AbstractObjectivesChronic pain has a substantial negative impact on work‐related outcomes, which underlines the importance of interventions to reduce the burden. Spinal cord stimulation (SCS) efficiently relieves pain in specific chronic pain syndromes and is recommended for treating failed back surgery syndrome (FBSS) or post‐surgical chronic back pain that is refractory to other treatments. To examine the impact of SCS in patients with FBSS on the return to work (RTW), we determined the RTW rate and the factors positively associated with the RTW.Materials and MethodsAmong 106 patients with FBSS who benefitted from SCS at a single institution in France between September 1999 and March 2010, we retrospectively included 59 who had stopped work at the time of SCS because of disability or sick leave and evaluated the RTW (rate and predictors, estimating odds ratios [ORs] and 95% confidence intervals [CIs]).ResultsThe mean (SD) post‐surgery follow‐up for the 59 patients (34 men; mean [SD] age 46.9 [7.4] years) was 7.5 (3.6) years (range 5–15). The RTW rate was 30.5%, with a median [IQR] recovery time of 5.5 months [3–8.5]. RTW was improved with functional improvement evolution (OR 1.1, 95% CI [1.01–1.1], p = 0.02) and was reduced with unemployment > 3 years (OR 0.1, 95% CI [0.01–0.7], p = 0.02).ConclusionsOur protocol for SCS for patients with FBSS, including a strict selection of patients and a multidisciplinary approach, led to good results, especially for the RTW. RTW should be a therapeutic goal, directly affecting indirect costs related to FBSS.
Positive crossover: Parent perceived partner responsiveness and health of youth with asthma
Authors: Bierstetel Sabrina J. , Farrell Allison K. , Tobin Erin T. , Kane Heidi S. , Imami Ledina , Zilioli Samuele , Slatcher Richard B. 
Published: January 2023

AbstractRomantic relationship functioning has implications that extend beyond the romantic dyad. This study tests whether a key positive aspect of relationships, perceived partner responsiveness, can cross over from parents' romantic relationships to children's health and well‐being via parenting behavior. In a sample of 112 youth with asthma and their primary caregivers, when caregivers perceived higher partner responsiveness in their romantic relationship, youth experienced improved self‐reported asthma symptoms, pulmonary functioning, and positive affect. The associations were robust while controlling for parents' relationship conflict and other relevant covariates, except for the pulmonary functioning outcome, which was instead predicted by parents' conflict. However, parenting behavior (i.e., positive and negative parenting) did not appear to mediate these links. This work highlights the importance of positive romantic relationship processes for youth health and well‐being, emphasizing the relevance of clinical intervention work and the need to continue investigating mechanisms through which these processes may be linked.
The effect of citrus planting orientation on the gradient and incidence of huanglongbing
Authors: Primiano Isabela Vescove , Eduardo Wellington Ivo , Amorim Lilian , Bergamin Filho Armando , Montesino Luiz Henrique , Bassanezi Renato Beozzo 
Published: January 2023

AbstractSuccessful primary spread of huanglongbing (HLB) within the citrus orchard occurs by the dispersal of the Asian citrus psyllid (ACP; Diaphorina citri) carrying the HLB bacterium “Candidatus Liberibacter asiaticus” (CLas) from external areas to blocks located in the orchard periphery. Higher ACP population is usually concentrated in a strip of up to 200 m from the orchard's edge. Consequently, a higher number of HLB‐symptomatic trees is also detected in this edge strip. Control strategies should be intensified in this strip to prevent further ACP dispersal and therefore to avoid more infected trees in inner blocks. The effect of the citrus planting direction, either parallel or perpendicular to the orchard's edge, was evaluated by comparing the HLB gradient and incidence in blocks located at the orchard's edge by the analysis of satellite images. Six areas with two neighbouring blocks (one planted in parallel and the other in a perpendicular direction) were evaluated in two periods. The exponential decay model was fitted to the HLB incidence at each distance in each block. Parameters from the model (a and b parameters) were similar between blocks planted in parallel (0.60 and 0.018 per metre, on average) and perpendicular (0.75 and 0.016 per metre, on average) planting directions. The total HLB incidence in blocks with a perpendicular planting direction (±30.3%) was higher than in blocks with a parallel planting direction (±22.8%). Overall, planting parallel to the orchard's edge is beneficial in reducing HLB incidence in orchards. This strategy can be integrated into HLB management programmes.
APLP2 is predominantly cleaved by β‐secretase and γ‐secretase in the human brain
Authors: Yanagida Kanta , Maruyama Riki , Tagami Shinji , Kudo Takashi , Okochi Masayasu , Fukumori Akio 
Published: January 2023

AbstractBackgroundAmyloid‐β peptide is well‐known as a pathogen of Alzheimer's disease, but its precursor, amyloid‐beta precursor protein (APP), remains unexplained 30 years after its discovery. APP has two homologues called amyloid precursor‐like protein 1 (APLP1) and amyloid precursor‐like protein 2 (APLP2), and shares a similar structural organisation with them and has partially overlapping functions. APP family proteins are essential for survival, shown by the crossbreeding analysis of knockout mice of APP family molecules, including APLP1 and APLP2. APLP2 is known to play the most important role among them, but the molecular metabolism of APLP2 is only partially understood. Here, we analysed ectodomain shedding and γ‐secretase cleavage of APLP2 by molecular biological and biochemical techniques.MethodWe analysed the culture supernatant of HEK293 cells overexpressing APLP2 and human cerebrospinal fluid. For the analysis of secreted APLP2 fragments, we raised the OA603 antibody that reacts with the juxtamembrane domain of APLP2. Substrate cleavage sites were identified by matrix assisted laser desorption/ionisation mass spectrometry.ResultsBy overexpressing in HEK293 cells, APLP2 undergoes ectodomain shedding at three sites in the extracellular region by α‐ and β‐secretase‐like activity and then is intramembranously cleaved at three sites by γ‐secretase. In particular, in shedding, α‐secretase‐like activity was dominant in HEK cells. Surprisingly, in human cerebrospinal fluid, APLP2‐derived metabolic fragments were mainly cleaved by β‐secretase‐like activity, not by α‐secretase‐like activity. Because APP is also mainly cleaved by beta‐site amyloid precursor protein cleaving enzyme 1 in neurons and APLP1 is expressed exclusively in neurons, these findings suggest that APP family proteins may play a common role via β‐secretase‐like cleavage in the central nerve system.ConclusionsThus, these findings may contribute to a better understanding of the role of APP family proteins in Alzheimer's disease.
The adaptation model of immunity: A new insight into aetiology and treatment of multiple sclerosis
Authors: Manjili Masoud H. 
Published: January 2023

AbstractCurrent research and drug development for multiple sclerosis (MS) is fully influenced by the self–nonself (SNS) model of immunity, suggesting that breakage of immunological tolerance towards self‐antigens expressed in the central nervous system (CNS) is responsible for pathogenesis of MS; thus, immune suppressive drugs are recommended for the management of the disease. However, this model provides incomplete understanding of the causes and pathways involved in the onset and progression of MS and limits our ability to effectively treat this neurological disease. Some pre‐clinical and clinical reports have been misunderstood; some others have been underappreciated because of the lack of a theoretical model that can explain them. Also, current immunotherapies are guided according to the models that are not designed to explain the functional outcomes of an immune response. The adaptation model of immunity is proposed to offer a new understanding of the existing data and galvanize a new direction for the treatment of MS. According to this model, the immune system continuously communicates with the CNS through the adaptation receptors (AdRs) and adaptation ligands (AdLs) or co‐receptors, signal IV, to support cell growth and neuroplasticity. Alterations in the expression of the neuronal AdRs results in MS by shifting the cerebral inflammatory immune responses from remyelination to demyelination. Therefore, novel therapeutics for MS should be focused on the discovery and targeting of the AdR/AdL axis in the CNS rather than carrying on with immune suppressive interventions.