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Participants
ankle sprain
All students (n = 114) enrolled in the subject were invited to participate and informed about the RCT including potential effects and demands of the intervention. Four students refused to participate in the study and eight students dropped out during the 14 weeks due to failure to complete the weekly questionnaire, gen...
PMC10559614
Methods
Participants were randomly allocated to three groups (intervention, placebo, and control). Students allocated into the intervention group wore a superficial neuromodulation device (© 2020 Irmoki) while students remained seated at rest following lectures at University. The device consists of 4 wireless receptors to be p...
PMC10559614
Data collection and analysis
fatigue, muscular soreness
Sociodemographical data were collected at baseline. Outcomes were gathered by means of an online questionnaire at baseline and after weeks 2, 4, 6, and 8 which retrieved data about fatigue, sleep quality, muscular soreness, stress level, and mood. In addition, participants in the intervention and placebo groups were as...
PMC10559614
Procedures related to the implementation of the UR programme
PMC10559614
Participants
From 114 students enrolled in the subject, ergo involved in the implementation of the UR teaching strategies for 14 weeks, the same four students who refused to participate on the RCT also refused to answer the UR outcome evaluation questionnaires at the end of the semester. Thus, 110 responses were collected. In addit...
PMC10559614
Methods
UR strategies were executed according to the subject´s syllabus. These were based, combined, and integrated on the theoretical topics described in Fig.  The strategies used during UR methodology implementationThe RCT, the implementation of UR strategies, and the evaluation were led by the two main lecturers of the subj...
PMC10559614
Data collection and outcome measures
At the end of the semester, an ad hoc questionnaire completed by participants in the study collected several outcomes focused on four dimensions: (a) the integration of research knowledge related to the theoretical contents; (b) the development of research competencies; (c) the level of self-efficacy about the skills t...
PMC10559614
Statistical analysis
Statistical analysis was conducted using Jamovi (v. 1.6.23, The Jamovi Project, Sydney, Australia). Descriptive statistics were calculated with proportions and frequencies and the distribution of the investigated variables was presented with bar diagrams.
PMC10559614
Results
mistakes
110 participants (sex: 48 M/54F; and age: 19.5 (1.63) years) completed the questionnaire about the impact of the UR teaching strategies. Figures  Results of the questionnaire: effect on integration of research knowledge related to the theoretical contents Results of the questionnaire: effect on the development of resea...
PMC10559614
Discussion
The research-based activity framed in a UR programme consisting of the implementation of a real RCT in which students were involved as participants and researchers, supervised by qualified lecturers, showed positive effects on the acquisition of theoretical content, the development of research competences, the level of...
PMC10559614
Limitations
BLIND
This study has some limitations. A systematic pre-post semester analysis and the lack of a control group of students without UR implementation are the most important. In this sense, a control group was very difficult to achieve because it was practically unfeasible to blind the students to the implementation of the RCT...
PMC10559614
Conclusion
This study presents a novel approach of the framework of UR in the unexplored healthcare discipline. Conducting an RCT is a challenging but valuable, useful, and effective way to integrate research and an inquiring attitude in physiotherapy students. Forms of teaching and learning focused on enhancing research and inqu...
PMC10559614
Acknowledgements
The authors thank all the students who participated as volunteers and the teachers who were involved for their contribution to the study. Likewise, we also want to thank the company Irmoki for the loan of the devices.
PMC10559614
Authors‘ contributions
A.A., I.S. and M.A. conducted the RCT. I.S. and I.V. analyzed and interpreted the data. A.A. was a major contributor in writing the manuscript. All authors read and approved the final manuscript.
PMC10559614
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
PMC10559614
Data Availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
PMC10559614
Declarations
PMC10559614
Ethics approval and consent to participate
This study was approved by the Research Ethics Committee of the University of Deusto (ETK-21/21–22) and was undertaken according to the Helsinki declaration. Informed consent was obtained from all subjects.
PMC10559614
Consent for publication
Not Applicable.
PMC10559614
Competing interests
The authors declare no competing interests.
PMC10559614
List of Abbreviations
Evidence-based practiceUndergraduate researchRandomised controlled trial
PMC10559614
Background
tumor
TUMOR, SOLID TUMORS
The mammalian target of rapamycin (mTOR) kinase, a central component of the PI3K/AKT/mTOR pathway, plays a critical role in tumor biology as an attractive therapeutic target. We conducted this first-in-human study to investigate the safety, pharmacokinetics (PK), and pilot efficacy of LXI-15029, an mTORC1/2 dual inhibi...
PMC10702058
Methods
intolerable adverse events, unresectable malignant solid tumors
DISEASE PROGRESSION
Eligible patients with advanced, unresectable malignant solid tumors after failure of routine therapy or with no standard treatment were enrolled to receive ascending doses (10, 20, 40, 60, 80, 110, and 150 mg) of oral LXI-15029 twice daily (BID) (3 + 3 dose-escalation pattern) until disease progression or intolerable ...
PMC10702058
Results
toxicity, hypertriglyceridemia, leukocytopenia
LEUKOCYTOPENIA, HYPERTRIGLYCERIDEMIA, DISEASE
Between June 2017 and July 2021, a total of 24 patients were enrolled. LXI-15029 was well tolerated at all doses. Only one dose-limiting toxicity (grade 3 increased alanine aminotransferase) occurred in the 150 mg group, and the maximum tolerated dose was 110 mg BID. The most common treatment-related AEs were leukocyto...
PMC10702058
Conclusions
SOLID TUMORS
LXI-15029 demonstrated reasonable safety and tolerability profiles and encouraging preliminary antitumor activity in Chinese patients with advanced malignant solid tumors, which warranted further validation in phase II trials.
PMC10702058
Trial registration
NCT03125746(24/04/2017),
PMC10702058
Keywords
PMC10702058
Methods
PMC10702058
Patient eligibility
ONCOLOGY, SOLID TUMORS
Patients were eligible for enrollment based on the following criteria: 1) 18 to 65 years of age; 2) histologically or cytologically diagnosed with advanced malignant solid tumors; 3) failure of routine therapy or without conventional standard therapy; 4) Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0...
PMC10702058
Study design
DLTs, neutropenia, fever, toxicity, PD, Cancer
ADVERSE EVENT, DISEASE PROGRESSION, NON-INFECTIOUS PNEUMONIA, NEUTROPENIA, ADVERSE EVENTS, THROMBOCYTOPENIA, DISEASE, SOLID TUMORS, ABNORMAL RENAL FUNCTION, ADVERSE EFFECT, CANCER
This was a single-center, open-label, phase I study to determine the safety, PK, the maximum tolerated dose (MTD), and preliminary efficacy of LXI-15029 monotherapy in Chinese patients with advanced malignant solid tumors. LXI-15029 capsules (provided by Shandong Luoxin Pharmaceutical Group Co., Ltd.) were administered...
PMC10702058
Endpoints
Tumors, SD
DISEASE, SECONDARY, TUMORS
The primary endpoint was the safety and tolerability of LXI-15029 monotherapy, including confirmation of MTD. The secondary endpoints were the PK parameters and investigator-assessed antitumor effect, including objective response rate (ORR, defined as the proportion of patients with complete response [CR] and partial r...
PMC10702058
PK analysis
BLOOD
Blood samples for PK analysis of LXI-15029 were collected on day 1 (pre-dose, 20 min, 40 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, and 48 h), cycle 1 day 8 (pre-dose), cycle 1 day 15 (pre-dose), and cycle 1 day 28 (pre-dose, 20 min, 40 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, and 12 h). The blood samples w...
PMC10702058
Patient assessments and evaluation
toxicity
All patients who received at least one dose of LXI-15029 were included in the safety and toxicity evaluations. Safety evaluations were performed on days 1, 8, 15, and 22 in cycle 1 and once every month after that. The safety assessments included vital signs, laboratory tests, and an electrocardiogram. Safety data were ...
PMC10702058
Statistical analysis
EVENT
All safety, tolerance, PK, and antitumor data from each dose group were tabulated and summarized according to the statistical analysis plan. The statistical analysis of the study was descriptive. The continuous variables were described as mean ± standard deviation or median (minimum, maximum). For the PK data, geometri...
PMC10702058
Results
PMC10702058
Preliminary efficacy data
PD, tumor, fibrosarcoma, SD
TUMOR, FIBROSARCOMA
Of the 24 participants who completed the treatment plan, 20 were evaluated for therapeutic efficacy. The tumor target lesions ranged from one to five. The lung, liver, and lymph nodes were the most common target lesion sites. Efficacy was evaluated based on the oncological evaluation analysis set and investigator asses...
PMC10702058
Discussion
tumor, pneumonia, cancers, stomatitis, hyperlipidemia, toxicities, cancer, hepatotoxicity, sarcoma, Cancer
TUMOR, PNEUMONIA, CANCERS, STILL, HYPERLIPIDEMIA, STOMATITIS, CANCER, DISEASE, HYPERGLYCEMIA, SARCOMA, BONE MARROW SUPPRESSION, NEUROENDOCRINE CARCINOMA, CANCER
The discovery of mTOR represents a fundamental breakthrough in the understanding of cell growth, metabolism, and disease [The serious toxicities of PI3K/AKT/mTOR inhibitors limit their clinical use and approval, including hyperglycemia, hyperlipidemia, bone marrow suppression, pneumonia, stomatitis, and hepatotoxicity ...
PMC10702058
Conclusions
SOLID TUMORS
LXI-15029 monotherapy demonstrated a favorable safety profile, tolerability, and preliminary antitumor activity in Chinese patients with advanced malignant solid tumors. PK-guided dosing might improve the efficacy and safety of LXI-15029, leading to further investigation in a larger population-based phase II study and ...
PMC10702058
Acknowledgements
We thank the participants in this study and gratefully acknowledge the collaboration of all investigators for their contributions. We thank W Wang, YH Wang, and MJ Li from Shandong Luoxin Pharmaceutical Group Co., Ltd. for assisting us with data analysis. We thank MedSci for editorial language assistance.
PMC10702058
Authors’ contributions
Conception and design: Q Li and B Xu. Development of methodology: Q Li, J Wang, and B Xu. Acquisition of data (acquired and managed patients, provided facilities, etc.): J Wang, L Gui, J Wang, Y Chi, Q Li, Y Mu, and B Xu. Analysis and interpretation of data (e.g., statistical analysis, computational analysis): Q Li and...
PMC10702058
Funding
This study was sponsored by Shandong Luoxin Pharmaceutical Group Co., Ltd., National Key Research and Development Program of China (No. 2018YFC1312101), and the Chinese Academy of Medical Science Innovation Fund for Medical Sciences(No. CIFMS-2021-I2M-1–014).
PMC10702058
Availability of data and materials
The datasets used and/or analyzed during the present study are available from the corresponding author upon reasonable request.
PMC10702058
Declarations
PMC10702058
Ethics approval and consent to participate
Cancer
CANCER
All interventions in this study were conducted in accordance with the Declaration of Helsinki guidelines of the International Conference for Harmonization/Good Clinical Practice guidelines and approved by the Independent Ethics Committee (IEC) of the National Cancer Center/Cancer Hospitals (Approved No.16–166/1245). Wr...
PMC10702058
Consent for publication
Not applicable.
PMC10702058
Competing interests
The authors declare no competing interests.
PMC10702058
References
PMC10702058
ABSTRACT.
infection, malaria infection, malnutrition, ’
MALARIA, INFECTION, MALARIA, INTERACTION, MALNUTRITION, FRANCIS
Financial Support: This study was supported by the Bill & Melinda Gates Foundation (Grant no. OPP1187628).Authors’ addresses: Elisabeth Gebreegziabher and Elodie Lebas, Francis I. Proctor Foundation, University of California San Francisco, San Francisco, CA, E-mails: The relationship between malaria infection and malnu...
PMC9978547
INTRODUCTION
malaria, Malnutrition, malaria infection, malnutrition
MALARIA, MALNUTRITION, UNDERNOURISHED, MALNUTRITION
Malnutrition and malaria continue to be major causes of morbidity and mortality in low- and middle-income countries. Globally, 8.9% of the population in 2019 was undernourished,The association between malaria infection and malnutrition is complex, and the directionality of these associations is poorly understood.To bet...
PMC9978547
MATERIALS AND METHODS
PMC9978547
Study design, setting, and population.
SECONDARY
For this secondary analysis, we used data from a randomized controlled trial (GAMIN) conducted between 2019 and 2020 to evaluate the potential effect of azithromycin on intestinal microbiome changes and child growth.
PMC9978547
Data collection and measures.
®
Data were collected at three time points: baseline, 2 weeks, and 6 months after enrollment. Anthropometric measures, including weight, height, and mid-upper arm circumference (MUAC) were taken at each study visit. Weight was measured using the SECA 847 scale (Chino, CA) to weigh infants and children to the nearest 0.1 ...
PMC9978547
Covariates.
infection, malnutrition
MALARIA, INFECTION, MALNUTRITION
Potential confounders of the association between malnutrition and malaria infection were selected a priori using a directed acyclic graph and based on previous literature.
PMC9978547
Statistical analysis methods.
malaria, infection, malaria infection, malnutrition
MALARIA, INFECTION, REGRESSION, MALNUTRITION
For all analyses, we used generalized estimating equations (GEEs) with robust standard errors to account for repeated observations in children. Six observations with extreme HAZ, WAZ, or WHZ scores (z-score > 6 or < −6) (To examine the effect of baseline anthropometric measures on point prevalence of malaria infection,...
PMC9978547
RESULTS
malaria infection statusMUAC
Characteristics of study participants are shown in Characteristics of children enrolled in the GAMIN trial in Burkina Faso by baseline malaria infection statusMUAC = mid-upper arm circumference.
PMC9978547
Effect of malaria infection on anthropometric measures.
infection, malaria infection
MALARIA, INFECTION
In the adjusted analysis, children with malaria infection at baseline had slightly lower mean height, MUAC, HAZ, and WAZ at 2 weeks and 6 months after enrollment compared with children without malaria infection, although these estimates did not reach statistical significance (Unadjusted and adjusted mean difference in ...
PMC9978547
Sensitivity analyses.
malaria, infection
MALARIA, INFECTION
In a sensitivity analysis controlling for age in months in models stratified by age groups (0–30 and 30–60 months), we found that results were very similar with regard to point estimates and statistical significance. The only change was for children aged 0–30 months, where the effect of baseline height on the prevalenc...
PMC9978547
DISCUSSION
malaria, infection, malaria infection
MALARIA, INFECTION
Our findings show that in this study population, baseline malaria infection did not affect growth at measurements 2 weeks and 6 months later. The effect of baseline anthropometric measures on the prevalence of malaria infection varied by child age. An increase in anthropometric measures at baseline increased the preval...
PMC9978547
Effect of malaria infection on anthropometric measures.
malaria
MALARIA, MALNUTRITION
Previous studies found mixed results regarding the effect of malaria on growth and malnutrition. Some studies found that malaria could impair growth.
PMC9978547
Effect of anthropometric measures on the prevalence of malaria infection.
malaria, malaria infection
MALARIA, INFECTION
For the effect of baseline anthropometric measures on the prevalence of malaria infection, in the adjusted analysis, there was no substantial increase or decrease in the prevalence of malaria infection for increasing anthropometric measures. Although the findings from previous studies are mixed, this result is in line ...
PMC9978547
Effect modification by age.
malaria, micronutrient deficiencies, malaria infection, protein-energy malnutrition, malnutrition
MALARIA, PROTEIN-ENERGY MALNUTRITION, MALNUTRITION
In this study, we found that the effect of baseline anthropometric measures on malaria infection prevalence varied by age. In those aged 30–60 months, there was a slight decrease in the prevalence of malaria infection as baseline measures increased, although the CIs did not reach statistical significance. Contrary to s...
PMC9978547
Strengths and limitations.
malaria infection, malnutrition
MALNUTRITION
This study had some limitations. First, we had a relatively small sample size, which could limit our statistical power to detect more subtle differences. However, several other studies, particularly longitudinal studies on this topic, also had similar sample sizes ranging between 202 and 847 participants.This study als...
PMC9978547
CONCLUSION
malaria, infection, malaria infection, malnutrition
MALARIA, INFECTION, MALNUTRITION
The effect of malnutrition on the prevalence of malaria infection may vary by age. The prevalence of malaria infection increased with increasing anthropometric measures among children aged 0–30 months, whereas it slightly decreased for children aged 30–60 months. Children aged 30–60 months with lower height, HAZ, and M...
PMC9978547
REFERENCES
PMC9978547
Purpose
pain
The aim of this study was to explore the isolated and combined effects of caffeine and citrulline malate (CitMal) on jumping performance, muscular strength, muscular endurance, and pain perception in resistance-trained participants.
PMC10468939
Methods
Using a randomized and double-blind study design, 35 resistance-trained males (
PMC10468939
Results
Compared to the placebo condition, isolated caffeine ingestion and co-ingestion of caffeine and CitMal significantly enhanced strength in 1RM bench press (Cohen’s
PMC10468939
Conclusion
Caffeine ingestion appears to be ergogenic for muscular strength and muscular endurance, while adding CitMal does not seem to further enhance these effects.
PMC10468939
Supplementary Information
The online version contains supplementary material available at 10.1007/s00394-023-03212-x.
PMC10468939
Keywords
Open access funding provided by Nord University
PMC10468939
Introduction
Caffeine is a highly popular ergogenic supplement used among athletes and non-athletes alike [Another supplement that has gained popularity in recent years is citrulline malate (CitMal), which represents a combination of L-citrulline and malic acid. L-citrulline is a non-essential amino acid primarily found in foods su...
PMC10468939
Methods
PMC10468939
Study design
PP pain
A randomized, double-blind, placebo-controlled, crossover trial (Fig. Overview of the study design. CMJ countermovement jump, RM repetitions maximum, SQ squat, BP bench press, AMRAP as many repetitions as possible, PP pain perceptionTimeline of test day. Questionnaire one was only given on familiarization (personal dat...
PMC10468939
Supplementation
All supplement conditions had a similar color and taste as they were mixed in 500 mL of Fun Light zero-calorie sweetened water (200 mL water and 300 mL non-caloric Fun light sweetener; Fun Light
PMC10468939
Adverse events
nausea, insomnia, disability
ADVERSE EVENTS, ADVERSE EVENT
The incidence and severity of adverse events were tracked during the testing sessions and throughout the remainder of the testing day. Specifically, during the testing sessions, the participants were encouraged to provide details about any adverse events (e.g., nausea). After the testing was completed, the participants...
PMC10468939
Measurements
PMC10468939
Countermovement jump
Each testing session started with the CMJ test on a force plate (Muscle lab, Ergotest Technology AS, Porsgrunn, Norway), which was used to evaluate jump height (cm), maximal power (W), rate of force development (kN/s), and peak force (N/kg). The CMJ was performed with feet shoulder-width apart and hands on the hips dur...
PMC10468939
1RM squat and bench press
Participants completed a 1RM test for both the squat and the bench press. In both exercises, a five sets warm-up protocol was utilized. In the first set, the participants completed several repetitions only with the barbell. Then, they completed 8, 6, 3, and 2 repetitions with loads amounting to 40%, 60%, 70%, and 80% o...
PMC10468939
Repetitions to failure and pain perception
Muscular failure, muscular failure, pain
Muscular endurance was evaluated by having the participants complete one set of repetitions to muscular failure in the squat and bench press using 60% of 1RM (from 1RM measured at each trial). During the set, the number of completed repetitions was counted out loud by the test leader. No breaks were allowed between rep...
PMC10468939
Statistical analyses
pain
The normality of data distribution was examined and confirmed using the Shapiro–Wilk test. A one-way analysis of variance (ANOVA) with repeated measures was conducted to explore the differences in performance outcomes (jump height, RFD, force, power, 1RM squat, 1RM bench press, number of repetitions in the squat and be...
PMC10468939
Results
PMC10468939
Countermovement jump
There was no significant main effect for CMJ height [F(3, 31) = 1.28;
PMC10468939
Muscular strength
Percent change in strength from placebo to caffeine and CitMal supplementation are presented in Fig. Percentage difference compared to placebo. Mean ± 95% confidence interval for Data are presented as group mean ± 95% confidence interval and individual data (dark points are males and white points are females) for Data ...
PMC10468939
Muscular endurance
pain
A significant main effect was found for the number of repetitions in the squat [F(3, 29) = 5.40, A significant main effect was found for the number of repetitions in the bench press [F(3, 33) = 7.66, There was no significant effect for pain perception following the completion of the repetitions to failure test in squat...
PMC10468939
Effectiveness of the blinding
In the effectiveness of the blinding evaluation, 46% (16/35), 46% (16/35), 26% (9/35), and 23% (8/35) of the participants correctly guessed the placebo, caffeine, caffeine and CitMal, and isolated CitMal conditions, respectively.
PMC10468939
Adverse events
dizziness, nausea, headache
ADVERSE EVENTS, EVENTS, ADVERSE EVENT
Seven adverse events were reported. These adverse events included headache (three), nausea (three), and dizziness (one). Six out of seven adverse events were reported as ‘probably’ when investigating the relationship to the supplements, and one adverse event was categorized as ‘definite’. Six adverse events that were c...
PMC10468939
Discussion
lower-body muscular endurance, pain
This is the first study to explore the effects of co-ingestion of caffeine (5 mg/kg) and CitMal (12 g) compared to either supplement in isolation or placebo. The main findings of this study were that the isolated ingestion of caffeine and co-ingestion of caffeine and CitMal was ergogenic for upper-body muscular strengt...
PMC10468939
Countermovement jump
Caffeine consumption alone and combined with CitMal did not influence jump height in our study. The lack of an effect on CMJ measurements is contrary to other research on caffeine [Besides the two treatments with caffeine, isolated ingestion of CitMal did not enhance jumping performance. Rapid force production is neces...
PMC10468939
Muscular strength
In the present study, caffeine alone and caffeine plus CitMal increased maximal strength compared to placebo. The ergogenic effects of caffeine on maximal strength are well-established [While caffeine provided an ergogenic effect, isolated CitMal ingestion did not influence maximal strength. In the currently available ...
PMC10468939
Muscular endurance
upper-body muscular endurance
STILL
Caffeine alone and caffeine co-ingested with CitMal improved lower-body and upper-body muscular endurance with a moderate effect size. While an ergogenic effect was found in both conditions, there were no differences between isolated caffeine vs. caffeine and CitMal combined.An ergogenic effect of caffeine on muscular ...
PMC10468939
Pain perception
pain
In the analysis for pain perception, we did not find a significant main effect. Previous studies observed that caffeine ingestion reduces pain perception [
PMC10468939
Adverse events
nausea, gastrointestinal problems
From a safety perspective, the co-ingestion of caffeine and CitMal could lead to gastrointestinal problems. Indeed, several participants reported nausea, but only following the combined ingestion of caffeine and CitMal. Interestingly, the incidence of side-effects was more common in women. The reason for that may be be...
PMC10468939
Limitations and strengths of the study
VASODILATATION
One of the limitations of the present study is that we did not measure plasma concentrations of caffeine and citrulline. Secondly, we did not measure possible mediators of the supplements that could have given more insight into the potential interactions between them, such as vasoconstriction and vasodilatation. Thirdl...
PMC10468939
Conclusions
This is the first study to explore the effects of co-ingestion of caffeine (5 mg/kg) and CitMal (12 g) compared to either supplement in isolation or placebo. We found that the ingestion of caffeine alone or combined with CitMal improved maximal strength and muscular endurance, but there were no additive effects of comb...
PMC10468939
Supplementary Information
Below is the link to the electronic supplementary material.Supplementary file1 (DOCX 153 KB)
PMC10468939
Funding
Open access funding provided by Nord University. No funding received.
PMC10468939
Data availability
On reasonable request data can be shared.
PMC10468939
Code availability
Not applicable.
PMC10468939
Declarations
PMC10468939
Conflict of interest
Markus Haugen has received payment for sports nutrition consultancy work with Empire Athletics, Norway. The other authors declare that there is no conflict of interest regarding the content of this article.
PMC10468939