Experimental Intervention Research Articles

If it walks like a duck…: Monitored Emergency Use of Unregistered and Experimental Interventions (MEURI) is research

Monitored Emergency Use of Unregistered and Experimental Interventions (MEURI) is an ethical framework developed by the WHO for using unproven interventions in public health emergencies outside the context of medical...

The impact of fine motor activities like playing musical instruments on the thickness and strength of the flexor digitorum muscle

BackgroundThis study aimed to explore the impact of occupational activities involving extensive finger movement on the muscular characteristics of the forearms. In particular, the flexor digitorum (FD) muscular thickness and strength asymmetry between right and left hand were compared between musicians and non-musicians.MethodsUltrasonography was employed to measure the thickness of the FD in each hand, while a validated custom-made device was used to assess the strength of the flexor and extensor digitorum (ED). Initially, muscle differences were estimated by computing the asymmetry index between dominant and non-dominant hands. To assess potential occupational disparities, comparisons of the asymmetry index were conducted between 25 right-handed instrumental musicians and 25 right-handed non-musicians.ResultsMusicians exhibited lower asymmetry between dominant and non-dominant hands in both FD thickness and ED strength when compared to non-musicians. This effect was particularly pronounced in musicians playing instruments that extensively use the left-hand fingers (e.g., violinists).ConclusionsOccupational activities, such as playing a musical instrument, can alter forearm muscle mass and strength distribution between dominant and non-dominant hands. This underscores the importance of considering occupational parameters in clinical or experimental interventions and musculoskeletal assessments.

Preparation and Characterization of Responsive Cellulose-Based Gel Microspheres for Enhanced Oil Recovery.

As an important means to enhance oil recovery, ternary composite flooding (ASP flooding for short) technology has achieved remarkable results in Daqing Oilfield. Alkalis, surfactants and polymers are mixed in specific proportions and injected into the reservoir to give full play to the synergistic effect of each component, which can effectively enhance the fluidity of crude oil and greatly improve the oil recovery. At present, the technology for further improving oil recovery after ternary composite flooding is not mature and belongs to the stage of technical exploration. The presence of alkaline substances significantly alters the reservoir's physical properties and causes considerable corrosion to the equipment used in its development. This is detrimental to both the environment and production. Therefore, it is necessary to develop green displacement control agents. In the reservoir environment post-ASP flooding, 2-(methylamino)ethyl methacrylate and glycidyl methacrylate were chosen as monomers to synthesize a polymer responsive to alkali, and then grafted with cellulose nanocrystals to form microspheres of alkali-resistant swelling hydrogel. Cellulose nanocrystals (CNCs) modified with functional groups and other materials were utilized to fabricate hydrogel microspheres. The product's structure was characterized and validated using Fourier transform infrared spectroscopy and X-ray diffraction. The infrared spectrum revealed characteristic absorption peaks of CNCs at 1165 cm-1, 1577 cm-1, 1746 cm-1, and 3342 cm-1. The diffraction spectrum corroborated the findings of the infrared analysis, indicating that the functional modification occurred on the CNC surface. After evaluating the swelling and erosion resistance of the hydrogel microspheres under various alkaline conditions, the optimal particle size for compatibility with the target reservoir was determined to be 6 μm. The potential of cellulose-based gel microspheres to enhance oil recovery was assessed through the evaluation of Zeta potential and laboratory physical simulations of oil displacement. The study revealed that the absolute value of the Zeta potential for gel microspheres exceeds 30 in an alkaline environment with pH values ranging from 7 to 14, exhibiting a phenomenon where stronger alkalinity correlates with a greater absolute value of Zeta potential. The dispersion stability spans from good to excellent. The laboratory oil displacement simulation experiment was conducted using a cellulose-based gel microsphere system following weak alkali ASP flooding within the pH value range from 7 to 10. The experimental interventions yielded recovery rates of 2.98%, 3.20%, 3.31%, and 3.38%, respectively. The study indicates that cellulose-based gel microspheres exhibit good adaptability in alkaline reservoirs. This research offers a theoretical foundation and experimental approaches to enhance oil recovery techniques post-ASP flooding.

Causal mediation analysis: How to avoid fooling yourself that X causes Y.

The purpose of many preclinical studies is to determine whether an experimental intervention affects an outcome through a particular mechanism, but the analytical methods and inferential logic typically used cannot answer this question, leading to erroneous conclusions about causal relationships, which can be highly reproducible. A causal mediation analysis can directly test whether a hypothesised mechanism is partly or completely responsible for a treatment's effect on an outcome. Such an analysis can be easily implemented with modern statistical software. We show how a mediation analysis can distinguish between three different causal relationships that are indistinguishable when using a standard analysis.

A systematic review to evaluate the risk of bias of meta-analyses reporting experimental educational interventions focused on academic performance

A systematic review to evaluate the risk of bias of meta-analyses reporting experimental educational interventions focused on academic performance

THE IMPACT OF LEUKOCYTE-PLATELET-RICH FIBRIN (L-PRF) ON THE ACCELERATION OF ORTHODONTIC TOOTH MOVEMENT

Objective. To determine the efficacy of leukocyte-platelet-rich fibrin (L-PRF) in orthodontics in achieving accelerated orthodontic tooth movement (OTM). Materials and methods. The search of records was carried out based on PRISMA methodological guidelines. Articles were identified using four electronic databases: PubMed, ScienceDirect, Web of Science, and Wiley Online Library. The search in selected databases was performed using combinations of the following keywords: (orthodontic tooth movement) AND (L-PRF) OR (leukocyte platelet-rich fibrin). The JBI critical appraisal tool was utilized to assess the quality of selected studies. Results. A total of 780 articles were identified. After eliminating duplicates and applying eligibility criteria, five studies were included in the review. The trials included 74 patients. Four studies showed a statistically significant increase in canine distalization with L-PRF on the experimental intervention sides compared to the control sides. However, one study indicated that L-PRF decreased the rate of OTM. The results of four studies show that L-PRF had the greatest effect on the distalization rate during the first 8 weeks; after 8 weeks, the rate of OTM decreased.

Making Emotional Intelligence Work at Work? An Experimental Intervention to Unlock Emotion Abilities

Making Emotional Intelligence Work at Work? An Experimental Intervention to Unlock Emotion Abilities

Impacts of digital social media detox for mental health: A systematic review and meta-analysis.

The impact of social media has been significant on various aspects of life, particularly mental health. Growing concerns about the adverse effects of social media use have prompted the exploration of experimental interventions, defined as digital detox interventions. However, it remains unclear whether digital detox interventions are effective for mental health outcomes. The aim of this study was to provide comprehensive insights into the effects of digital detox interventions on various mental health outcomes, including depression, life satisfaction, stress, and mental well-being. Following the PRISMA guidelines, systematic searches were carried out in online databases, including PubMed and ScienceDirect, within the publication range of 2013 and 2023. A total of 2578 titles and abstracts were screened, and 10 studies were included in the analysis. A risk of bias assessment was conducted using RoB 2.0 and the Newcastle-Ottawa scale, while statistical analysis was conducted using RevMan 5.4.1. Our data indicated a significant effect of digital detox in mitigating depression with the standardized mean difference (SMD: -0.29; 95%CI: -0.51, -0.07, p=0.01). No statistically significant effects were discerned in terms of life satisfaction (SMD: 0.20; 95%CI: -0.12, 0.52, p=0.23), stress (SMD: -0.31; 95%CI: -0.83, 0.21, p=0.24), and overall mental well-being (SMD: 0.04; 95%CI: -0.54, 0.62, p=0.90). These data underscore the nuanced and selective influence of digital detox on distinct facets of mental health. In conclusion, digital detox interventions significantly reduce depressive symptoms, suggesting that intentional reduction or cessation of digital engagement may help alleviate contributing factors. However, no statistically significant effects were observed in mental well-being, life satisfaction, and stress. This discrepancy may be due to the complex nature of these constructs, involving various factors beyond the scope of digital detox interventions.

Adaptive group behavior of Fragile X mice in unfamiliar environments

Fragile X Syndrome (FXS) stands out as a prominent cause of inherited intellectual disability and a prevalent disorder closely linked to autism. FXS is characterized by substantial alterations in social behavior, encompassing social withdrawal, avoidance of eye contact, heightened social anxiety, increased arousal levels, language deficits, and challenges in regulating emotions. Conventional behavioral assessments primarily focus on short-term interactions within controlled settings. In this study, we conducted a comprehensive examination of the adaptive group behavior of Fmr1 KO male mice over a three-day period, without introducing experimental interventions or task-based evaluations. The data unveiled intricate behavioral anomalies, with the most significant changes manifesting during the initial adaptation to unfamiliar environments. Notably, certain behaviors exhibited a gradual return to typical patterns over time. This dynamic Fmr1 KO phenotype exhibited heightened activity, featuring increased exploration, amplified social interest, and an unconventional approach to social interactions characterized by a higher frequency of shorter engagements. These findings contribute to the growing understanding of social behavior in individuals with FXS and underscore the significance of comprehending their adaptive responses in various environmental contexts.

Designing cities for everyday nature.

The motivations for incorporating nature into the design of cities have never been more compelling. Creating experiences with nature that occur every day (everyday nature) in cities could help reverse the fate of many threatened species and connect people with nature and living cultural traditions. However, this requires more than just urban greening; it involves ensuring daily doses of nature in a way that also supports nonhuman organisms. A major shift in the way nature is conceived of and is made part of the design of cities is required. Principles include reconsidering nature as a development opportunity rather than a constraint and eliminating offsetting of biodiversity site values. Processes include using biodiversity-sensitive design frameworks and establishing meaningful professional engagement among ecologists, planners, and designers. Challenges include design obstacles, conflicts between nature and people (e.g., safety, disease, and noise) that require careful management, and socioeconomic and political considerations (e.g., Global North vs. Global South). Research to interrogate the multiple benefits of nature in cities can complement experimental interventions, ultimately supporting better urban design and creating much more resiliently built environments for people and nature.

Effects of technology-aided teaching mode on the development of CT skills of EFL students in Higher Vocational Colleges: A case study of English argumentative writing

With the increasing application of technology in education, exploring the value of technology-aided teaching modes in promoting students' development of critical thinking (CT) skills has become more prominent. This study targets English as a Foreign Language (EFL) students in Higher Vocational Colleges (HVCs) to empirically investigate the effects of technology-aided teaching on their development of CT skills. Utilizing the method of equal-group comparative teaching experiment, this study divided students into control and experimental groups and implemented various technology-aided teaching interventions in the experimental group. The results reveal that the application of technology has a positive impact on the development of CT skills and improvement in English argumentative writing among EFL students. Based upon these findings, this study proposes a teaching mode “problem-based learning context creating - viewpoints expressing - viewpoint questioning - collaborative resolution - reflective learning,” aiming to provide insights for effectively conducting CT teaching for EFL students under a technological environment.

Low-frequency sounds combined with motor imagery elicits a transient disruption of force performance: A path to neuromotor reprogramming?

The effectiveness of motor imagery (MI) training on sports performance is now well-documented. Recently, it has been proposed that a single session of MI combined with low frequency sound (LFS) might enhance muscle activation. However, the neural mechanisms underlying this effect remain unknown. We set up a test-retest intervention over the course of 2 consecutive days to evaluate the effect of (i) MI training (MI, n = 20), (ii) MI combined with LFS (MI + LFS, n = 20), and (iii) a control condition (CTRL, n = 20) on force torque produced across repeated maximal voluntary contractions of the quadriceps before (Pretest), after (Posttest) and at +12 h (Retention) post-intervention. We collected the integrated electromyograms of the quadriceps muscles, as well as brain electrical potentials during each experimental intervention. In the CTRL group, total force torque decreased from Pretest to Retention and from Posttest to Retention. By contrast, there was an increase between Posttest and Retention in both MI + LFS and MI groups (both ηP2 = 0.03, p < 0.05). Regression analyses further revealed a negative relationship between force performance and EEG activity in the MI + LFS group only. The data support a transient interference of LFS on cortical activity underlying the priming effects of MI practice on force performance. Findings are discussed in relation to the potential for motor reprogramming through MI combined with LFS.

Quality of Informed Consent in Phase III Clinical Trials in Portugal: The Participants' Perspective.

Some studies show that participants do not always fully understand the informed consent form (ICF), which is one of the reasons for dropouts. This study aimed to adapt the Quality of Informed Consent (QuIC) questionnaire into a valid instrument to be applied to the Portuguese population and to measure its reliability and validity in the Portuguese population, by applying it to a sample of participants in controlled trials. The QuIC questionnaire was developed to assess the quality of informed consent in clinical trials and consists of two parts, addressing both the objective (part A) and the subjective (part B) understanding. After being translated and validated into Portuguese, it was implemented in 100 cardiac participants of phase III clinical trials in a University Hospital Center. The QuIC-PT questionnaire showed excellent stability over time and good validity. All patients evaluated their participation and their health positively and recognized the main purpose of the clinical trial. Almost all participants understood their role in helping future patients and the purpose of the trial and realized that, by signing the ICF, they were participating in a clinical trial. However, none of them knew that their experimental treatment was not proven to be the best alternative for their condition. The QuIC-PT questionnaire seems to be a valid and useful instrument to evaluate the participants' understanding of the ICF. In this study, we found that some concepts, like 'study protocol' or 'randomization', were not well understood by participants when signing the ICF, especially by participants with lower education levels. They also believed that the experimental intervention would solve their health condition. Greater awareness about the importance of the informed consent process and ICF is necessary so that participants can fully understand the protocol, especially the risks involved, and their rights as participants.

Endometriotic tissue fragments are viable after cryopreservation in an ex vivo tissue model recapitulating the fibrotic microenvironment.

Is it possible to establish an ex vivo endometriosis model using cryopreserved endometriotic tissue fragments? Cryopreserved endometriotic tissue fragments remain viable after thawing and during at least 3days of culture and can therefore be used to establish an ex vivo endometriosis model to efficiently test potential therapeutic agents. Endometriosis is the most prevalent benign gynecologic disease with an enormous societal burden; however, curative therapies are still lacking. To efficiently test potential new therapies, an ex vivo model based on previously cryopreserved endometriotic tissue that recapitulates the different endometriosis subtypes and their microenvironment is highly desirable. Endometriotic tissue fragments of three different subtypes were obtained from 28 patients by surgical resection. After cryopreservation and thawing, viability and metabolic activity of these tissue fragments were assessed. Viability was compared with fresh fragments from 11 patients directly after surgical removal. Experimental intervention studies were performed in cryopreserved and thawed tissue fragments from two patients to confirm the usability of these tissues for ex vivo intervention studies. Endometriotic tissue fragments (n = 45) were cryopreserved according to three different protocols. After thawing, fragments were cultured for 24 h. A resazurin-based assay was performed to assess the metabolic activity of the tissue fragments. In addition, cell type-specific viability was analyzed by VivaFix, Hoechst 33342, and α-smooth muscle actin immunofluorescence staining and confocal microscopy. The presence of endometriosis was histologically confirmed based on hematoxylin-eosin staining. Cryopreserved and thawed tissue fragments were treated for 72 h with pirfenidone or metformin and COL1A1 and CEMIP gene expressions were assessed using RT-PCR and RT-qPCR, either in the whole tissue fragments or in myofibroblasts isolated by laser capture microdissection. Metabolic activity of endometriotic tissue fragments obtained from peritoneal (PER), ovarian (OMA), and deep (DE) endometriotic lesions was well preserved after cryopreservation in a dimethyl sulfoxide-based medium and was comparable with fresh tissue fragments. Relative metabolic activity compared to fresh tissue was 70% (CI: 92-47%) in PER, 43% (CI: 53-15%) in OMA and 94% (CI: 186-3%) in DE lesions. In fragments from PE lesions 92% (CI: 87-96%), from OMA lesions 95% (CI: 91-98%), and from DE lesions 88% (CI: 78-98%) of cells were viable after cryopreservation and thawing followed by a 24-h culture period. Differences in gene expression of fibrotic markers COL1A1 and CEMIP after 72-h treatment with pirfenidone or metformin could be detected in whole tissue fragments and in isolated myofibroblasts, indicating that cryopreserved and thawed endometriotic tissue fragments are suitable for testing anti-fibrotic interventions. N/A. Viability and metabolic activity of the endometriotic tissue fragments may have been partially compromised by damage sustained during the surgical procedure, contributing to inter-sample variance. The storage of viable endometriotic tissue fragments for later usage in an ex vivo model creates the possibility to efficiently test potential new therapeutic strategies and facilitates the exchange of viable endometriotic tissue between different research laboratories. This study was not financially supported by external funding. The authors declare no competing interest. N/A.

The Impact on Anxiety Symptoms of an Immersive Virtual Reality Remediation Program in Bipolar Disorders: A Randomized Clinical Trial.

Background: The objective of this work is to investigate the effectiveness of a cognitive remediation intervention on anxiety symptoms in people with bipolar disorder and the therapeutic effect on people whose anxiety symptoms were above the threshold for a screener and whose comorbidity could be identified as an anxiety disorder. Methods: The experimental intervention included 24 sessions (around 45 min each), two for each week over three months. The entire program was inspired by user-centered rehabilitation principles in a recovery-oriented perspective and an approach to bipolar disorder in an evolutionary and non-discriminating vision. The primary outcomes measure the score of the Zung Self-Rating Anxiety Scale (SAS), hypothesizing a higher decrease in the experimental group than in the control group. The survey has been conducted per the CONSORT guidelines for feasibility studies. Results: We evaluate a decrease in the overall SAS score from T0 to T1 to be higher in the experimental group compared to the control group, indicating an improvement in anxiety symptoms (p < 0.0001). Conclusions: The study suggests that virtual reality could have a role in treating anxiety symptoms and disorders in young adults with bipolar disorders or anxiety symptoms in people with hyperactivity and novelty-seeking behaviorsunder stress and high risk for bipolar disorder.

Low-cost, portable, easy-to-use kiosks to facilitate home-cage testing of nonhuman primates during vision-based behavioral tasks.

Nonhuman primates (NHPs), especially rhesus macaques, have significantly contributed to our understanding of the neural computations underlying human vision. Besides the established homologies in the visual brain areas between these species and our ability to probe detailed neural mechanisms in monkeys at multiple scales, NHPs' ability to perform human-like visual behavior makes them an extremely appealing animal model of human vision. Traditionally, such behavioral studies have been conducted in controlled laboratory settings, offering experimenters tight control over variables like luminance, eye movements, and auditory interference. However, in-lab experiments have several constraints, including limited experimental time, the need for dedicated human experimenters, additional lab space requirements, invasive surgeries for headpost implants, and extra time and training for chairing and head restraints. To overcome these limitations, we propose adopting home-cage behavioral training and testing of NHPs, enabling the administration of many vision-based behavioral tasks simultaneously across multiple monkeys with reduced human personnel requirements, no NHP head restraint, and monkeys' unrestricted access to experiments. In this article, we present a portable, low-cost, easy-to-use kiosk system developed to conduct home-cage vision-based behavioral tasks in NHPs. We provide details of its operation and build to enable more open-source development of this technology. Furthermore, we present validation results using behavioral measurements performed in the lab and in NHP home cages, demonstrating the system's reliability and potential to enhance the efficiency and flexibility of NHP behavioral research.NEW & NOTEWORTHY Training nonhuman primates (NHPs) for vision-based behavioral tasks in a laboratory setting is a time-consuming process and comes with many limitations. To overcome these challenges, we have developed an affordable, open-source, wireless, touchscreen training system that can be placed in the NHPs' housing environment. This system enables NHPs to work at their own pace. It provides a platform to implement continuous behavioral training protocols without major experimenter intervention and eliminates the need for other standard practices like NHP chair training, collar placement, and head restraints. Hence, these kiosks ultimately contribute to animal welfare and therefore better-quality neuroscience in the long run. In addition, NHPs quickly learn complex behavioral tasks using this system, making it a promising tool for wireless electrophysiological research in naturalistic, unrestricted environments to probe the relation between brain and behavior.

Adipose Tissue Derivatives in Peripheral Nerve Regeneration after Transection: A Systematic Review.

Peripheral nerve injury (PNI) is increasingly prevalent and challenging to treat despite advances in microsurgical techniques. In this context, adipose tissue derivatives, such as adipose-derived stem cells, nanofat, and stromal vascular fraction have been gaining attention as potential allies in peripheral nerve regeneration. This study aims to explore the use of adipose tissue derivatives in nerve regeneration following peripheral nerve transection in murine models. Thus, we assess and synthesize the key techniques and methods used for evaluating the obtained nerve regeneration to guide future experimental research and clinical interventions. A systematic review was conducted in February 2024, adhering to the Cochrane and PRISMA 2020 guidelines, using the PubMed, SciELO, and LILACS databases. The focus was on experimental studies involving adipose tissue derivatives in nerve regeneration in animal models post-transection. Only experimental trials reporting nerve regeneration outcomes were included; studies lacking a comparator group or evaluation methods were excluded. Out of 273 studies initially identified from MEDLINE, 19 were selected for detailed analysis. The average study included 32.5 subjects, with about 10.2 subjects per intervention subgroup. The predominant model was the sciatic nerve injury with a 10 mm gap. The most common intervention involved unprocessed adipose-derived stem cells, utilized in 14 articles. This review underscores the significant potential of current methodologies in peripheral nerve regeneration, particularly highlighting the use of murine models and thorough evaluation techniques.

Acute Effect of Simultaneous Exercise and Cognitive Tasks on Cognitive Functions in Elderly Individuals with Mild Cognitive Impairment.

The increasing prevalence of age-related cognitive decline, alongside the aging global population, underscores the urgent need for innovative and effective preventative strategies. While the advantages of combining physical and cognitive exercises have been recognized as a promising approach to address these socioeconomic challenges, the acute effects of such interventions on cognitive functions remain understudied. This study aimed to investigate whether simultaneous physical and cognitive exercise has a greater beneficial impact on the cognitive functions of older adults with mild cognitive impairment (MCI) than physical exercise alone or reading activities. A total of 44 MCI patients (75% females aged between 65 and 75 years) were randomly assigned to one of three groups: aerobic exercise alone (EG group, n = 15), aerobic combined with cognitive exercises (CEG group, n = 15), or a reading task for controls (CG group, n = 14). Attention, memory, and problem solving were assessed before and after the acute intervention using the Tower of Hanoi, Digit Span, and Stroop tasks, respectively. Statistical analysis revealed that both of the experimental interventions appeared to enhance cognitive function scores (p < 0.05), except for the number of moves in the Tower of Hanoi task, where no improvement was noted. In contrast, no significant differences in any cognitive performance measures were observed following the reading session. Notably, the CEG group exhibited a more pronounced positive impact, especially on working memory. This advantage was specifically evident in the digit span tasks, where significantly greater percentage gains were found in the CEG than in the CG (p = 0.02), while no significant difference existed between the EG and CG. Simultaneous combined exercise has proven to be a more effective method than aerobic physical exercise alone for improving cognitive function. The results of this study are recommended for inclusion in clinical practice guidelines to maintain the mental health of older adults, as simultaneous exercise seems to offer a time-efficient strategy to enhance cognitive performance in adults with MCI.

The Clinical Effect and Safety of Dihuang Decoction in Henoch-Schönlein Purpura Compared With Different Traditional Programs: A Network Meta-Analysis.

This systematic review aims to evaluate the therapeutic efficacy of Dihuang decoction (DD), anti-inflammatory drugs (AIDs), blood circulation improvement drugs (BCIDs), and conventional therapy (CT) in the management of Henoch-Schönlein purpura (HSP)and to establish their comparative effectiveness rankings. Using the Population, Intervention, Comparison, Outcome, Study (PICOS) design framework, we developed a detailed search strategy. The literature search included databases such as PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, Weipu Journal Data, and the Chinese Biomedical Database, covering studies published up to June2024. We included randomized controlled trials that featured the DD as the experimental intervention, with three remaining treatments as comparators.Our analysis encompassed 63 studies with 5,435 participants, divided into 2,817 in the experimental group and 2,618 in the control group. The network meta-analysis suggested that theDD potentially surpasses AIDs, BCIDs, and CT in the management of HSP. This conclusion is supported by its superior SUCRA (Surface Under the Cumulative Ranking) scores across various measures, including the overall effective rate of medication, time to relief or disappearance of the rash, incidence of adverse reactions, time to relief or disappearance of abdominal pain, time to relief or disappearance of arthritic swelling or pain, IgA levels, and the relapse rate within six months (SUCRA scores: 100.0%, 88.3%, 79.8%, 94.4%, 99.9%, 88.3%, and 95.4%, respectively). In terms of overall effectiveness rate, the SUCRA efficacy rankings are as follows: DD > AIDs > AIDs+BCID > BCID > CT. Regarding rash relief and regression time, the SUCRA efficacy rankings are as follows: DD > CT > AIDs+BCID > AIDs. For the incidence rate of adverse reactions, the SUCRA efficacy rankings are as follows: DD > CT > AIDs > BCID > AIDs+BCID. For the relief and disappearance of abdominal pain, the SUCRA efficacy rankings are as follows: DD > CT > AIDs+BCID > AIDs. In terms of relief and disappearance of joint swelling and pain, the SUCRA efficacy rankings are as follows: DD > AIDs+BCID > AIDs. Regarding IgA changes, the SUCRA efficacy rankings are as follows: DD > CT > BCID > AIDs+BCID > AIDs. For the six-month recurrence rate, the SUCRA efficacy rankings are as follows: DD > AIDs > AIDs+BCID > CT. The DD appears to be a more effective alternative for treating HSP compared to AIDs, BCIDs, and CT.We hope that this study will provide better assistance to clinical practice.

Time of sample collection is critical for the replicability of microbiome analyses.

As the microbiome field moves from descriptive and associative research to mechanistic and interventional studies, being able to account for all confounding variables in the experimental design, which includes the maternal effect1, cage effect2, facility differences3, as well as laboratory and sample handling protocols4, is critical for interpretability of results. Despite significant procedural and bioinformatic improvements, unexplained variability and lack of replicability still occur. One underexplored factor is that the microbiome is dynamic and exhibits diurnal oscillations that can change microbiome composition5-7. In this retrospective analysis of 16S amplicon sequencing studies in male mice, we show that sample collection time affects the conclusions drawn from microbiome studies and its effect size is larger than those of a daily experimental intervention or dietary changes. The timing of divergence of the microbiome composition between experimental and control groups is unique to each experiment. Sample collection times as short as only 4 hours apart can lead to vastly different conclusions. Lack of consistency in the time of sample collection may explain poor cross-study replicability in microbiome research. The impact of diurnal rhythms on the outcomes and study design of other fields is unknown but likely significant.