bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of an 8-week multimodal exercise program on ground reaction forces and plantar pressure during walking in boys with autism spectrum disorder
Authors: Dehghani Mahrokh , Jafarnezhadgero Amir Ali , Darvishani Mohamad Abdollahpour , Aali Shirin , Granacher Urs 
Published: March 2023

Abstract
Background
Autism spectrum disorder is a developmental disability with first signs appearing in children aged 3 years and younger. Given that autism spectrum disorder is accompanied by a broad range of symptoms such as impaired sensory, neurological, and neuromotor functions, it appears plausible to argue that an intervention program focusing on multimodal exercise rather than single-mode exercise might be more effective in treating this wide variety of symptoms.

Objective
The aim of this study was to evaluate the effects of a multimodal exercise program entitled Sports, Play, and Active Recreation for Kids on variables of ground reaction forces and plantar pressure during walking in boys with autism spectrum disorder.

Methods
Twenty-four autism spectrum disorder boys aged 7–11 years were recruited and randomly allocated into an intervention or a waiting control group. Sports, Play, and Active Recreation for Kids was conducted over a period of 8 weeks with three weekly sessions. This training protocol includes aerobic dance and jump rope exercises as well as running games. Pre- and post-training, ground reaction forces and plantar pressure variables were recorded while walking at a constant walking speed of 0.9 m/s using a foot scan embedded in a 15-m walkway.

Results
Significant group-by-time interactions were found for the first peak of vertical ground reaction force, loading rate, and peak pressure at the medial heel region (all p = 0.001–0.49, d = 0.89–1.40). Post-hoc analyses showed significant pre-post decreases for the first peak of vertical ground reaction force (p = 0.001, d = 1.27), loading rate (p = 0.009, d = 1.11), and peak pressure at the medial heel region (p = 0.021, d = 1.01).

Conclusions
Our results suggest that a joyful and multimodal exercise program has positive effects on kinetic walking characteristics of autism spectrum disorder boys. Accordingly, we recommend to implement this type of exercise in prepubertal autism spectrum disorder boys to improve gait kinetics.

Trial registration
Iranian Registry of Clinical Trials IRCT20170806035517N4. Registered on November 8, 2021. This study was approved by the Ethical Committee of the University of Mohaghegh Ardabili, Ardabil, Iran (IR.UMA.REC.1400.019). The study was conducted in accordance with the latest version of the Declaration of Helsinki.
The integration of rapid qualitative research in clinical trials: reflections from the ward-based goal-directed fluid therapy (GDFT) in acute pancreatitis feasibility trial
Authors: Vindrola-Padros Cecilia , Froghi Farid , Gopalan Vignesh , Maruthan Sachan , Filipe Helder , McNeil Margaret , Garcia Sara Mingo , Davidson Brian ,   on behalf of the GAP trial team
Published: March 2023

AbstractBackgroundThere has been an increase in the integration of qualitative studies in randomised controlled trials. The purpose of this article is to reflect on our experience of carrying out a rapid qualitative study during a feasibility trial of goal-directed fluid therapy (GDFT) in patients with acute pancreatitis, including our sharing of emerging findings and the use of these findings by the trial team.MethodsThe study was designed as a rapid feedback evaluation and combined interviews with staff and patients who took part in the trial.FindingsThe rapid qualitative study pointed to common problems in trial recruitment among multiple sites, where lack of engagement of clinical teams across sites might impact negatively on patient recruitment. The article describes how the use of rapid feedback loops can be used as the trial is ongoing to inform changes in implementation. It also covers the potential challenges of working rapidly and collaborative with the trial team.ConclusionsRapid feedback evaluations can be used to generate findings across all stages of trial design and delivery. Additional research is required to explore the implementation of this research design in other settings and trial designs.
Master protocol to assess the long-term safety in kidney transplant recipients who previously received Medeor’s cellular immunotherapy products: the MDR-105-SAE
Authors: Kant Sam , Kaufman Dixon B. , Micsa Lenuta , Brennan Daniel C. 
Published: March 2023

Abstract
Background
Immunosuppression in transplantation continues to be associated with a multitude of adverse effects. Induction of immune tolerance may be a viable strategy to reduce dependence on immunosuppression. Various trials are currently underway to assess the efficacy of this strategy. However, long-term safety data for these immune tolerance regimes has yet to be established.

Methods/design
At the completion of primary follow-up of various Medeor kidney transplant studies, subjects receiving cellular immunotherapy products will be followed annually as per protocolized schedule for up to an additional 84 months (7 years) to evaluate long-term safety. Long-term safety will be assessed by summarizing incidence of serious adverse events, adverse events leading to study withdrawal and hospitalization rates.

Discussion
This extension study will be an important step in evaluating safety issues pertaining to immune tolerance regimens, long-term effects of which are largely unknown. These data are essential for furthering an unrealized goal of kidney transplantation- graft longevity without the adverse effects from long-term immunosuppression. The study design utilizes the methodology of a master protocol, wherein multiple therapies can be assessed simultaneously with accompanied gathering of long-term safety data.
Capnographic monitoring reduces hypoxia incidence in older patients undergoing gastrointestinal endoscopy under propofol sedation: study protocol for a multicenter randomized controlled trial
Authors: Lian Qiuyue , Chen Shaoyi , Cheng Xiangyang , Zhang Jie , Yu Weifeng , Zhou Renlong , Su Diansan 
Published: March 2023

Abstract
Background
Hypoxia is a very common adverse event that occurs during gastrointestinal endoscopy under sedation, especially in older patients, owing to limited reservation of heart, brain, lung, and other organs. Prolonged or severe hypoxia can cause ischemia of the coronary artery and permanent nervous system damage, and even result in death. Hence, it is imperative to reduce or prevent hypoxia during gastrointestinal endoscopy under sedation in older patients. Although several oxygen delivery methods would reduce hypoxia during this procedure, early detection of respiratory depression and early administration of intervention would be the best method to reduce or even confirm the hypoxia. Capnographic monitoring is reportedly more sensitive for detecting respiratory depression before the onset of hypoxia than the current clinical routine monitoring of pulse oxygen saturation; however, its effect is controversial. Therefore, in this study, we aimed to improve the safety of gastrointestinal endoscopy under sedation in older patients.

Methods
A multicenter, randomized, single-blind, two-arm parallel-group, controlled with an active comparator, interventional superiority clinical trial will be conducted to evaluate the impact of an additional capnographic monitoring-based intervention on the incidence of hypoxia in older patients. Patients (n = 1800) scheduled for gastrointestinal endoscopy with propofol sedation will be randomly assigned to either a control or interventional arm, wherein standard or capnographic monitoring is implemented, respectively.

Discussion
This study primarily aims to examine whether an additional capnographic monitoring-based intervention can reduce the incidence of hypoxia in older patients during gastrointestinal endoscopy under propofol and sufentanil sedation. The results of this study may extensively impact gastrointestinal endoscopy under sedation and the development of associated guidelines.

Trial registration
ClinicalTrials.gov NCT05030870. Registered on September 1, 2021.
A randomised study of rituximab and belimumab sequential therapy in PR3 ANCA-associated vasculitis (COMBIVAS): design of the study protocol
Authors: McClure Mark E. , Gopaluni Seerapani , Wason James , Henderson Robert B. , Van Maurik Andre , Savage Caroline C.O. , Pusey Charles D. , Salama Alan D. , Lyons Paul A. , Lee Jacinta , Mynard Kim , Jayne David R. , Jones Rachel B. ,   on behalf the COMBIVAS investigators
Published: March 2023

AbstractBackgroundSequential B cell-targeted immunotherapy with BAFF antagonism (belimumab) and B cell depletion (rituximab) may enhance B cell targeting in ANCA-associated vasculitis (AAV) through several mechanisms.MethodsStudy design: COMBIVAS is a randomised, double-blind, placebo-controlled trial designed to assess the mechanistic effects of sequential therapy of belimumab and rituximab in patients with active PR3 AAV. The recruitment target is 30 patients who meet the criteria for inclusion in the per-protocol analysis. Thirty-six participants have been randomised to one of the two treatment groups in a 1:1 ratio: either rituximab plus belimumab or rituximab plus placebo (both groups with the same tapering corticosteroid regimen), and recruitment is now closed (final patient enrolled April 2021). For each patient, the trial will last for 2 years comprising a 12-month treatment period followed by a 12-month follow-up period.Participants: Participants have been recruited from five of seven UK trial sites. Eligibility criteria were age ≥ 18 years and a diagnosis of AAV with active disease (newly diagnosed or relapsing disease), along with a concurrent positive test for PR3 ANCA by ELISA.Interventions: Rituximab 1000 mg was administered by intravenous infusions on day 8 and day 22. Weekly subcutaneous injections of 200 mg belimumab or placebo were initiated a week before rituximab on day 1 and then weekly through to week 51. All participants received a relatively low prednisolone (20 mg/day) starting dose from day 1 followed by a protocol-specified corticosteroid taper aiming for complete cessation by 3 months.Outcomes: The primary endpoint of this study is time to PR3 ANCA negativity. Key secondary outcomes include change from baseline in naïve, transitional, memory, plasmablast B cell subsets (by flow cytometry) in the blood at months 3, 12, 18 and 24; time to clinical remission; time to relapse; and incidence of serious adverse events. Exploratory biomarker assessments include assessment of B cell receptor clonality, B cell and T cell functional assays, whole blood transcriptomic analysis and urinary lymphocyte and proteomic analysis. Inguinal lymph node and nasal mucosal biopsies have been performed on a subgroup of patients at baseline and month 3.DiscussionThis experimental medicine study provides a unique opportunity to gain detailed insights into the immunological mechanisms of belimumab-rituximab sequential therapy across multiple body compartments in the setting of AAV.Trial registrationClinicalTrials.gov NCT03967925. Registered on May 30, 2019.
Core protocol for the adaptive Platform Trial In COVID-19 Vaccine priming and BOOsting (PICOBOO)
Authors: McLeod C. , Ramsay J , Flanagan K. L. , Plebanski M. , Marshall H. , Dymock M. , Marsh J. , Estcourt M. J. , Wadia U. , Williams P. C. M. , Tjiam M. C. , Blyth C. , Subbarao K. , Nicholson S. , Faust S. , Thornton R. B. , Mckenzie A. , Snelling T. L , Richmond P. 
Published: March 2023

Abstract
Background
The need for coronavirus 2019 (COVID-19) vaccination in different age groups and populations is a subject of great uncertainty and an ongoing global debate. Critical knowledge gaps regarding COVID-19 vaccination include the duration of protection offered by different priming and booster vaccination regimens in different populations, including homologous or heterologous schedules; how vaccination impacts key elements of the immune system; how this is modified by prior or subsequent exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and future variants; and how immune responses correlate with protection against infection and disease, including antibodies and effector and T cell central memory.

Methods
The Platform Trial In COVID-19 priming and BOOsting (PICOBOO) is a multi-site, multi-arm, Bayesian, adaptive, randomised controlled platform trial. PICOBOO will expeditiously generate and translate high-quality evidence of the immunogenicity, reactogenicity and cross-protection of different COVID-19 priming and booster vaccination strategies against SARS-CoV-2 and its variants/subvariants, specific to the Australian context. While the platform is designed to be vaccine agnostic, participants will be randomised to one of three vaccines at trial commencement, including Pfizer’s Comirnaty, Moderna’s Spikevax or Novavax’s Nuvaxovid COVID-19 vaccine. The protocol structure specifying PICOBOO is modular and hierarchical. Here, we describe the Core Protocol, which outlines the trial processes applicable to all study participants included in the platform trial.

Discussion
PICOBOO is the first adaptive platform trial evaluating different COVID-19 priming and booster vaccination strategies in Australia, and one of the few established internationally, that is designed to generate high-quality evidence to inform immunisation practice and policy. The modular, hierarchical protocol structure is intended to standardise outcomes, endpoints, data collection and other study processes for nested substudies included in the trial platform and to minimise duplication. It is anticipated that this flexible trial structure will enable investigators to respond with agility to new research questions as they arise, such as the utility of new vaccines (such as bivalent, or SARS-CoV-2 variant-specific vaccines) as they become available for use.

Trial registration
Australian and New Zealand Clinical Trials Registry ACTRN12622000238774. Registered on 10 February 2022.
Impact of corticosteroids on the duration of ventilatory support during severe acute exacerbations of chronic obstructive pulmonary disease in patients in the intensive care unit: a study protocol for a multicentre, randomized, placebo-controlled, double-blind trial
Authors: Ferré Alexis , Thille Arnaud W. , Mekontso-Dessap Armand , Similowski Thomas , Legriel Stéphane , Aegerter Philippe , Demoule Alexandre ,   The Réseau Européen de Recherche en Ventilation Artificielle (REVA) research network
Published: March 2023

Abstract
Background
Patients who are admitted to the intensive care unit (ICU) for severe acute exacerbations of chronic obstructive pulmonary disease (COPD) have poor outcomes. Although international clinical practice guidelines cautiously recommend the routine use of systemic corticosteroids for COPD exacerbations, data are scarce and inconclusive regarding their benefit for most severe patients who require mechanical ventilation in the ICU. Furthermore, corticosteroids may be associated with an increased risk of infection, ICU-acquired limb weakness, and metabolic disorders.

Methods and analysis
This study is an investigator-initiated, multicentre, randomized, placebo-controlled, double-blind trial comparing systemic corticosteroids to placebo during severe acute exacerbations of COPD in patients who require mechanical ventilation in French ICUs. A total of 440 patients will be randomized 1:1 to methylprednisolone (1 mg/kg) or placebo for 5 days, and stratified according to initial mechanical ventilation (non-invasive or invasive), pneumonia as triggering factor, and recent use of systemic corticosteroids (< 48 h). The primary outcome is the number of ventilator-free days at day 28, defined as the number of days alive and without mechanical invasive and/or non-invasive ventilation between randomization and day 28. Secondary outcomes include non-invasive ventilation (NIV) failure rate, duration of mechanical ventilation (invasive and/or NIV), circulatory support (vasopressor), outcomes related to corticosteroid adverse events (severe hyperglycaemia, gastrointestinal bleeding, uncontrolled arterial hypertension, ICU-acquired weakness, ICU-acquired infections, and delirium), lengths of ICU and hospital stay, ICU and hospital mortality, day 28 and day 90 mortality, number of new exacerbation(s)/hospitalization(s) between hospital discharge and day 90, and dyspnoea and comfort at randomization, ICU discharge, and day 90. Subgroup analyses for the primary outcome are planned according to stratification criteria at randomization.
Enantioseparation, quantification, molecular docking and molecular dynamics study of five β-adrenergic blockers on Lux-Cellulose-2 column
Authors: Saleh Ola Ahmed , Badawey Amr Mohamed , Aboul-Enein Hassan Y. , Fouad Marwa Ahmed 
Published: March 2023

AbstractEnantioseparation of five β-adrenergic blockers was studied using two mobile phases on a cellulose tris(3‐chloro‐4‐methylphenylcarbamate) (Lux-Cellulose-2) chiral column in normal phase mode. The first mobile phase composed of n-hexane: ethanol: diethylamine 60: 40: 0.1 by volume has successfully resolved the chromatographic peaks of three pairs of β-adrenergic blockers namely, bisoprolol, carvedilol and atenolol. A mixture of n-hexane: ethanol: diethyl amine 75: 25: 0.1 by volume was used as the second mobile phase to separate the four pairs of enantiomers, metoprolol, carvedilol, nebivolol and atenolol with high resolution values. The mobile phases were pumped at a flow rate 1 mL/min with column temperature 25 °C using a UV detector at 230 nm. Molecular docking simulations of the five pairs of enantiomers was carried out in the cavities of the chiral stationary phase to gain a better understanding of the interaction between analyte enantiomers and chiral stationary phase and to better understand the mechanism of chiral recognition. According to the results, hydrogen bond interactions and π-π- interactions were the main types of interaction involved in the chiral recognition. Molecular dynamics simulation was performed to investigate the solvent effect on the interaction of the five pair of enantiomers in the chiral stationary phase cavity under dynamic conditions.
Rapid screening of secondary aromatic metabolites in Populus trichocarpa leaves
Authors: Harman-Ware Anne E. , Martin Madhavi Z. , Engle Nancy L. , Doeppke Crissa , Tschaplinski Timothy J. 
Published: March 2023

Abstract
Background
High-throughput metabolomics analytical methodology is needed for population-scale studies of bioenergy-relevant feedstocks such as poplar (Populus sp.). Here, the authors report the relative abundance of extractable aromatic metabolites in Populus trichocarpa leaves rapidly estimated using pyrolysis-molecular beam mass spectrometry (py-MBMS). Poplar leaves were analyzed in conjunction with and validated by GC/MS analysis of extracts to determine key spectral features used to build PLS models to predict the relative composition of extractable aromatic metabolites in whole poplar leaves.

Results
The Pearson correlation coefficient for the relative abundance of extractable aromatic metabolites based on ranking between GC/MS analysis and py-MBMS analysis of the Boardman leaf set was 0.86 with R2 = 0.76 using a simplified prediction approach from select ions in MBMS spectra. Metabolites most influential to py-MBMS spectral features in the Clatskanie set included the following compounds: catechol, salicortin, salicyloyl-coumaroyl-glucoside conjugates, α-salicyloylsalicin, tremulacin, as well as other salicylates, trichocarpin, salicylic acid, and various tremuloidin conjugates. Ions in py-MBMS spectra with the highest correlation to the abundance of extractable aromatic metabolites as determined by GC/MS analysis of extracts, included m/z 68, 71, 77, 91, 94, 105, 107, 108, and 122, and were used to develop the simplified prediction approach without PLS models or a priori measurements.

Conclusions
The simplified py-MBMS method is capable of rapidly screening leaf tissue for relative abundance of extractable aromatic secondary metabolites to enable prioritization of samples in large populations requiring comprehensive metabolomics that will ultimately inform plant systems biology models and advance the development of optimized biomass feedstocks for renewable fuels and chemicals.
Unveiling the underlying molecular mechanisms of high lutein production efficiency in Chlorella sorokiniana FZU60 under a mixotrophy/photoautotrophy two-stage strategy by transcriptomic, physiological, and biochemical analyses
Authors: Ma Ruijuan , Zhang Zhen , Fang Hong , Liu Xinyu , Ho Shih-Hsin , Xie Youping , Chen Jianfeng 
Published: March 2023

AbstractBackgroundChlorella sorokinianaFZU60 is a promising lutein producing microalga. A mixotrophy/photoautotrophy two-stage strategy can achieve high biomass concentration at stage 1 and high lutein content at stage 2, leading to excellent lutein production efficiency inC. sorokinianaFZU60. However, the underlying molecular mechanisms are still unclear, restraining the further improvement of lutein production.ResultsIn this study, physiological and biochemical analysis revealed that photochemical parameters (Fv/Fm and NPQ) and photosynthetic pigments contents increased during the shift from mixotrophy to photoautotrophy, indicating that photosynthesis and photoprotection enhanced. Furthermore, transcriptomic analysis revealed that the glyoxylate cycle and TCA cycle were suppressed after the shift to photoautotrophy, leading to a decreased cell growth rate. However, the gene expression levels of photosynthesis, CO2fixation, autophagy, and lutein biosynthesis were upregulated at the photoautotrophy stage, demonstrating that microalgal cells could obtain more precursor to synthesize lutein for enhancing photosynthesis and reducing reactive oxygen species.ConclusionsThe findings help to elucidate the molecular mechanisms for high lutein production efficiency ofC. sorokinianaFZU60 under the mixotrophy/photoautotrophy strategy, identify key functional genes responsible for lutein biosynthesis, and shed light on further improvement of lutein production by genetic or metabolic engineering in future studies.
Range of metastrongylids (superfamily Metastrongyloidea) of public health and veterinary concern present in livers of the endemic lizard Gallotia galloti of Tenerife, Canary Islands, Spain
Authors: Izquierdo-Rodriguez Elena , Anettová Lucia , Hrazdilová Kristýna , Foronda Pilar , Modrý David 
Published: March 2023

Abstract
Background
Endemic lizards of the genus Gallotia are of high ecological value to the terrestrial ecosystem of the archipelago of the Canary Islands, being potent seed spreaders as well as an important component of the diet of other vertebrates. The endemic lizard Gallotiagalloti in Tenerife has recently been reported to be a paratenic host of Angiostrongyluscantonensis, an invasive metastrongylid with zoonotic potential that is associated with rats as definitive hosts. However, microscopic examination of G.galloti tissue samples also revealed the presence of other metastrongylid larvae inside granulomas on the liver of this reptile. The aim of this study was to investigate the presence of helminths other than A.cantonensis in tissues of G.galloti from Tenerife.

Methods
A multiplex-nested PCR targeting the internal transcribed spacer 1 was designed that enabled the species-specific detection of A.cantonensis, Angiostrongylusvasorum, Aelurostrongylusabstrusus, Crenosomastriatum and Crenosomavulpis. Liver samples from 39 G.galloti were analysed.

Results
Five metastrongylids were detected: A.cantonensis (15.4% of samples analysed), A.vasorum (5.1%), Ae.abstrusus (30.8%), C.striatum (30.8%) and undetermined metastrongylid sequences (12.8%). Co-infection was highly prevalent among the lizards which tested positive.

Conclusions
The study provides a new specific tool for the simultaneous detection of a range of metastrongylids of veterinary importance as well as new data on the circulation of metastrongylids in an ecosystem dominated by lizards.

Graphical Abstract