Category: Statistics

Parasit Vectors. 2025 Jun 9;18(1):217. doi: 10.1186/s13071-025-06865-1.

ABSTRACT

BACKGROUND: Toxoplasma gondii is a widespread parasite that can infect almost all vertebrate species including humans, causing variable clinical symptoms from asymptomatic infection to serious diseases. Though extensive research has been done in recent decades, the prevention and control of T. gondii continue to present substantial challenges. Herbal medicines have long been a rich source of chemical entities and may provide new avenues for drug discovery against T. gondii. Thus, this study was performed to investigate the anti-T. gondii effect of two monomers, beta, beta-dimethylacrylshikonin (DMAS) and isobutyrylshikonin (IBS), extracted from the roots of a widely distributed and used medical plant.

METHODS: The cytotoxicity of DMAS and IBS on Vero cells was evaluated using the MTT assay, and the toxicity in mice was assessed on the basis of the changes of body weight combined with the histopathologic examinations on spleen, liver, and kidney. The effects of DMAS and IBS on mice against T. gondii acute infection were evaluated by combining survival curves with splenic histopathologic examination. Ultrastructural change in T. gondii tachyzoites post co-incubation in vitro was observed by electron microscopy. ACT1-quantitative polymerase chain reaction (qPCR) was conducted to quantify T. gondii tachyzoites, including proliferation and the inhibitory efficacy of DMAS and IBS. Invasion and attachment, intracellular proliferation, and parasitophorous vacuole viability evaluations were conducted to assess the effects on the asexual life cycle of T. gondii. In addition, untargeted metabolomics analysis was performed to clarify the underlying mechanisms by which DMAS and IBS act against this parasite.

RESULTS: Both DMAS and IBS, with higher half-maximal cytotoxic concentration (CC₅₀) values, exhibited concentration-dependent cytotoxicity in Vero cells and significantly inhibited the intracellular proliferation of T. gondii in vitro, showing lower half-maximal inhibitory concentration (IC₅₀) values and higher selectivity index (SI) values. DMAS showed a statistically more potent effect than IBS, but both were not significantly more potent than that of pyrimethamine (PM). The tachyzoites exhibited severe ultrastructural damage following treatment with DMAS or IBS. Metabolomics analysis indicated that this abnormal biological lesion was caused by the disruptions in purine and pyrimidine metabolism pathways in T. gondii, with mechanisms likely differing from that of PM. In vivo, a dose of 1.5 mg/kg of DMAS showed no significant toxicity in Kunming (KM) mice, with no significant pathological damage or weight loss. At this dosage, both DMAS and IBS significantly alleviated the splenic hyperemia and statistically prolonged the survival times of T. gondii-infected mice.

CONCLUSIONS: This study demonstrated that DMAS and IBS have an inhibitory effect on T. gondii infection in vitro and in vivo, probably associated with the disruption of nucleotide metabolism in the parasite. These results highlight that the two monomers, in particular DMAS, hold promise as a potential therapeutic medicine for toxoplasmosis.

PMID:40490809 | DOI:10.1186/s13071-025-06865-1

Stem Cell Res Ther. 2025 Jun 9;16(1):297. doi: 10.1186/s13287-025-04432-0.

ABSTRACT

BACKGROUNDS: Exosomes is a promising cell-free therapy for Diabetic peripheral neuropathy (DPN) that imposes long-term negative effects on patients’ finances, mental health, and quality of life. We conducted a meta-analysis to assess the therapeutic effects of exosomes (such as SCs-derived, FCs-derived, BMSCs-derived, MSCs-derived, and Plasma-derived) on DPN.

METHODS: We searched nine databases from inception to February 2025, then two researchers independently screened studies, extracted data, and assessed the quality of included studies using SYRCLE’s tool. The outcome indicators consisted of at least one of the three key DPN endpoints (electrophysiology, behavioural assessment, and nerve structure) based on the Neurodiab guidelines. R 4.4.2 software was used to conduct all statistical analyses.

RESULTS: 11 studies were identified, and the risk of bias in most studies was unclear generally. Pooled analyses demonstrated that exosome improved the nerve conduction velocity [MCV (SMD = 4.71 [2.18;7.25], P = 0.0003; I²= 91.8%), SCV (SMD = 1.07 [0.30;1.85], P = 0.0069; I²= 85.3%)], may restore IENFD [SMD = 1.46 [-0.85; 3.77], P = 0.2164; I²=88.7%], alleviated neuropathic pain [mechanical allodynia (SMD= -0.27 [-1.02;0.47], P = 0.4697; I² = 85.0%), thermal hyperalgesia (SMD= -1.48 [-2.45;-0.50], P = 0.003; I² = 88.4%)], ameliorated vascular function [blood flow perfusion in plantar (SMD = 2.84 [0.89; 4.80], P = 0.0043; I² = 74.9%), blood flow perfusion in sciatic nerves (SMD = 2.62 [0.80; 4.43], P = 0.0047; I² = 75.9%), vessel density (SMD = 2.69 [0.90; 4.49], P = 0.0032; I² = 0%)], and restored the peripheral nerve structure [sciatic nerve fiber diameter (SMD = 3.29 [1.61; 4.96], P = 0.0066; I² = 75.5%), axon diameter (SMD = 2.26 [1.64; 2.88], P < 0.0001; I² = 54.3%), myelin sheath thickness (SMD = 2.56 [1.39; 3.72], P < 0.0001; I² = 73.0%), g-ratio (SMD= -1.64 [-3.28; 0.00], P = 0.0502; I² = 34.17)]. Furthermore, after exosome therapy, the expressions of NF-200 (SMD = 2.57 [0.39; 4.75], P = 0.0210; I² = 33.0%), MBP (SMD = 2.27 [-1.49; 6.02], P = 0.1064; I² = 59.0%), and S-100β (SMD = 1.90 [0.09; 3.72], P = 0.0399; I² = 32.5%) evaluating axonal regeneration and remyelination increased significantly. Notably, high-glucose pretreatment of exosomes significantly attenuated these effects, while genetic overexpression modifications or novel dressings-mediated delivery partially counteracted this suppression.

CONCLUSIONS: Exosome therapy provides a novel therapeutic strategy for the benefit of neurovascular remodeling and functional recovery of DPN, especially when used in conjunction with exosome modification and novel dressings. To bridge the translational gap between preclinical and clinical studies, future research should conduct more large-scale, meticulously designed preclinical trials adhering to ARRIVE criteria before proceeding to clinical translation, to enhance translational rigor and mitigate risks associated with variability in study design.

PMID:40490808 | DOI:10.1186/s13287-025-04432-0

Contracept Reprod Med. 2025 Jun 9;10(1):36. doi: 10.1186/s40834-025-00364-5.

ABSTRACT

BACKGROUND: The use of a dual contraception method (DCM) is recommended as an effective method to prevent Human Immunodeficiency Virus (HIV) transmission and the adverse consequences of pregnancy in people living with HIV infection. In developing countries like Ethiopia, contraception use is subjected to sociocultural, knowledge, and accessibility-related factors that influence consumption. Accordingly, this study aims to explore the magnitude of DCM use and factors related to consumption in HIV-positive women of reproductive age.

METHODS: An institutional-based cross-sectional study was conducted at Hawassa University Comprehensive Specialized Hospital. The study used a systematic sampling technique to select 268 consenting participants. Data was collected using a semi-structured questionnaire via face-to-face interview. Descriptive statistics were used to present background information, and a hierarchical binary logistic regression was used to investigate DCM use and associated factors. Results with a p-value less than 0.05 are considered significant. All data analysis was performed using SPSS version 26.

RESULTS: The magnitude of DCM use was 30% (95% CI; 24.0-35.0). After controlling for potential confounding variables women aged 15-36 years, (AOR = 8.65, 95% CI: 2.60, 28.75) and 37-40 years, (AOR = 6.25, 95% CI, 2.08, 18.82), women with no fertility desire (AOR = 8.34, 95% CI: 3.95, 17.61), women who have open discussions with their partners (AOR = 5.71, 95% CI: 2.15, 15.11), and women with knowledge of CD4 count (AOR = 2.94, 95% CI: 1.35, 6.38) were found to have a higher likelihood of DCM use.

CONCLUSIONS: The magnitude of DCM use among reproductive-age HIV-positive women was unsatisfactory. This provided an enormous window for counseling and reproductive health promotion measures. Interventional studies and strengthening of ART and family planning services must be customized to target the major social, cultural, and knowledge barriers identified in this study to enhance the practice of DCM use.

PMID:40490805 | DOI:10.1186/s40834-025-00364-5

Alzheimers Res Ther. 2025 Jun 10;17(1):130. doi: 10.1186/s13195-025-01764-0.

ABSTRACT

BACKGROUND: The growing prevalence of dementia emphasizes the need for effective prevention strategies. Although the partial efficacy of multidomain interventions for dementia prevention has been demonstrated, understanding the characteristics of individuals who benefit most from these interventions is crucial for optimizing resource allocation. This study investigated the association between participants’ genetic backgrounds and the effectiveness of multidomain interventions for preventing dementia.

METHODS: This study utilized data from the Japan-Multimodal Intervention Trial for the Prevention of Dementia (J-MINT), where older adults with mild cognitive impairment underwent 18 months of multidomain intervention. The intervention included exercise, nutrition, cognitive stimulation, social participation, and vascular risk management. Participants who completed the J-MINT intervention and had genetic data, including whole-genome sequencing (WGS), were analyzed. Using Japanese polygenic risk scores (PRSs) for Alzheimer’s disease, participants were stratified into high- and low-genetic-risk groups. Cognitive composite score (CPS) improvement rates at 6-, 12-, and 18-months were compared between intervention and control groups, with subgroup analyses performed by age (< 75 and $\ge$ 75 years). Additionally, a comprehensive variant analysis using WGS was conducted to identify genetic signals potentially associated with the intervention’s effectiveness.

RESULTS: Among 289 participants analyzed (168 aged < 75 years; 121 aged ≥ 75 years), 99 were classified into the high-risk PRS group (56 intervention, 43 control) and 190 into the low-risk PRS group (92 intervention, 98 control). For participants aged ≥ 75 years, no statistically significant differences in CPS improvement rates were observed between the intervention and control groups, regardless of PRS classification. However, in participants aged < 75, those in the high-risk PRS group showed significant CPS improvement at the 6-month follow-up. Additionally, analysis of 9,978,605 genetic variants identified two loci, ID3 and LMO1 (rs2067053 and rs201082658), with suggestive associations (P < 1 × 10⁻⁴) to reduced intervention effectiveness.

CONCLUSIONS: This study highlighted the utility of PRS in predicting cognitive improvement following multidomain interventions and identified genetic variants that may influence the intervention’s effectiveness. The findings provide a valuable foundation for personalized dementia prevention strategies.

PMID:40490801 | DOI:10.1186/s13195-025-01764-0

Harm Reduct J. 2025 Jun 9;22(1):102. doi: 10.1186/s12954-025-01250-8.

ABSTRACT

BACKGROUND: The United States is experiencing an intersecting crisis of structural inequities, record levels of homelessness, and a surging fourth wave of the opioid epidemic. People experiencing unsheltered homelessness (PEUH) are at particularly high risk of opioid-related death. Although naloxone is a key tool for preventing overdose fatalities, PEUH face significant barriers to accessing and retaining it. This study examined the acceptability of a novel overdose education and naloxone distribution (OEND) intervention implemented during Kern County’s 2024 Point-in-Time (PIT) unsheltered count. As part of the initiative, volunteers were offered optional OEND training prior to distributing naloxone to PEUH during the annual PIT Count.

METHODS: Naloxone distribution was tracked, and PIT Count volunteers were recruited via convenience sampling to complete a post-intervention electronic survey. The survey assessed acceptability using domains from the Theoretical Framework of Acceptability. Descriptive statistics and thematic analysis were used to evaluate responses related to OEND training and naloxone distribution.

RESULTS: Of 111 survey initiators, 94 met eligibility criteria. Most respondents (71.3%) participated in the OEND training, and nearly two-thirds (64.9%) distributed naloxone. Among those with prior overdose experience (n = 26), 88.5% had taken bystander action, most often administering naloxone or calling 911. Training participants reported positive affective attitudes (mean = 1.57), high perceived effectiveness (mean = 1.58), low burden (mean = 1.89), and low opportunity cost (mean = 4.40 on a reverse scale), with slightly lower self-efficacy (mean = 2.23). Overall acceptability was high (mean = 1.45). Among naloxone distributors, responses indicated strong comfort (mean = 1.6), confidence (mean = 1.7), coherence (mean = 1.6), and acceptability (mean = 1.8), along with low burden (mean = 1.9) and opportunity cost (mean = 4.5). Over 87% expressed willingness to distribute naloxone in future PIT Counts. Non-distributors cited reasons such as lack of opportunity, participant refusal, and discomfort. Open-ended responses suggested improvements in training availability, logistics, and messaging for PEUH.

CONCLUSIONS: Naloxone training and distribution during the PIT Count was feasible and highly acceptable. These findings support broader implementation to improve naloxone access and reduce overdose deaths among PEUH, and they provide a foundation for future effectiveness studies.

PMID:40490800 | DOI:10.1186/s12954-025-01250-8

Ital J Pediatr. 2025 Jun 9;51(1):185. doi: 10.1186/s13052-025-02048-x.

NO ABSTRACT

PMID:40490792 | DOI:10.1186/s13052-025-02048-x

BMC Health Serv Res. 2025 Jun 9;25(1):818. doi: 10.1186/s12913-025-12815-5.

ABSTRACT

BACKGROUND/PURPOSE: To examine how the choice of rural measurements affects estimates of hospitalization rates for depression and substance use disorders (SUD).

METHODS: We conducted cross-sectional analyses using the 2018 State Inpatient Database (SID) for 5 states, including Arizona, Kentucky, Maryland, Washington, and Florida, to determine how (1) estimates of hospitalization rates for depression and SUDs; and (2) patient characteristics among those hospitalized differ. Five measurements of rurality including rural-urban commuting areas (RUCA) codes, core-based statistical areas (CBSA), urban-rural category four (URCategory4) and two definitions of rural urban continuum codes (RUCC) were used. For each measurement, we calculated frequencies and percentages for age, race, sex, and insurance type. We conducted Spearman’s rank correlations to compare associations and internal agreement. We created an UpSet chart to visualize the overlap in different measurements.

RESULTS: There were 152,771 hospitalizations for depression and 43,760 hospitalizations for SUDs. The percentage of hospitalizations for depression or SUD differed significantly (3.2-8.1% for depression and 5.0-11.6% for SUDs ) based on rurality measure. Race and insurance characteristics of those identified as rural varied by rural measurement for depression and SUD hospitalizations. Spearman’s correlations were higher for hospitalizations for SUD than for depression, ranging from r = 0.61 (RUCC and RUCA) to r = 0.99 (CBSA and URCategory4).

CONCLUSIONS: Different rurality measurements result in differing estimates of hospitalizations for SUD or depression. Stakeholders should be aware that the choice of rural measurements can impact policy decisions and resource allocation for programs intended to improve care in rural areas.

PMID:40490786 | DOI:10.1186/s12913-025-12815-5

J Orthop Surg Res. 2025 Jun 9;20(1):578. doi: 10.1186/s13018-025-05953-3.

ABSTRACT

OBJECTIVE: The optimal surgical approach for tibial avulsion fractures of the posterior cruciate ligament (PCL) remains controversial. This study aimed to compare the clinical outcomes of four techniques: arthroscopic suture fixation, arthroscopic loop plate fixation, open reduction with cannulated screw fixation, and open reduction with anchor suture bridge fixation.

METHODS: A retrospective review was conducted of 73 patients treated between January 2019 and December 2023 using one of four surgical techniques: arthroscopic suture fixation (Group A, n = 26), arthroscopic loop plate fixation (Group B, n = 14), open reduction with cannulated screw fixation (Group C, n = 16), and open reduction with anchor suture bridge fixation (Group D, n = 17). Demographic data, operative time, pre- and postoperative visual analog scale (VAS) pain scores, Lysholm scores, International Knee Documentation Committee (IKDC) scores, knee range of motion (ROM), and postoperative complications were analyzed.

RESULTS: No significant differences were observed in baseline demographic data among the four groups (P >.05). Operative time was shortest in Group D (60.41 ± 12.39 min), significantly less than in the other groups (P =.0001). At 3 months postoperatively, all groups demonstrated significant improvements in VAS, Lysholm, and IKDC scores (P <.0001); however, intergroup differences were not statistically significant (P >.05). Group A demonstrated significantly less ROM recovery compared with the other groups (P =.0171). At final follow-up, further improvements in functional scores and ROM were observed in all groups, with no significant intergroup differences (P >.05). Complication rates differed significantly among the groups (P =.0361), with Group D reporting the lowest rate (0%) and Group A the highest (34.6%).

CONCLUSION: No significant differences were found in overall clinical outcomes among the four techniques. However, open reduction with anchor suture bridge fixation demonstrated favorable operative efficiency and complication profile, suggesting clinical advantages in selected patients.

TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2500100641. Registration Date: 2025-04-11, Retrospectively registered.

PMID:40490779 | DOI:10.1186/s13018-025-05953-3

Malar J. 2025 Jun 9;24(1):184. doi: 10.1186/s12936-025-05438-y.

ABSTRACT

BACKGROUND: The presence of a community effect in cluster randomized trials of malaria vector control interventions has led to the implementation of “buffer zones” around clusters to limit the potential for contamination between interventions. No consensus has been reached on how large these buffers need to be to encapsulate the effect.

METHODS: Nested within a phase-III cluster randomized malaria vector control trial in Northwest Tanzania, this study aims to determine the presence and spatial range of community effects from long-lasting insecticidal net (LLIN) and indoor residual spraying (IRS) interventions on household-level malaria infection in trial clusters four months post-intervention. Effective spatial range estimates of intervention community effects were compared to the 300m buffer distance implemented to limit intervention spillover between clusters in the trial. Geographically-weighted adjusted odds of malaria infection in children aged 0.5-14 years were determined four months post community-level intervention with a randomized allocation comprising one of two LLIN products (Olyset^TM LN: 1000mg/m² permethrin or Olyset^TM Plus LN: 400 + permethrin 800mg/m²) with either IRS (Actellic^®300CS: 1000mg/m² micro-encapsulated pirimiphos-methyl) or no IRS. Robust semivariances were calculated for each of 48 intervention clusters and fit to semivariogram models by Weighted Least Squares.

RESULTS: 6440 children from 2785 households were included in the geographically-weighted logistic regression. Prevalence of Plasmodium falciparum infection was 45.9% in the study population. Twenty (20) clusters had significant residual effect ranges, 13 of which were fit to Sine Hole Effect models, indicating periodicity in the study area. Effective range estimates for the study area had a median value of 1210 m (IQR: 958-1691). Clusters with IRS had a higher median range value: 1535 m (IQR: 976-3398) than those without IRS: 1168m (IQR: 829-1504).

CONCLUSIONS: Significant semivariogram model range estimates extended beyond the trial buffer sizes by a median average of 868 m in LLIN intervention clusters and 1235 m for IRS clusters. This presents a contamination, or spillover, potential for all trialed intervention types that may reduce the statistical power to detect difference between trial arms. Future studies should consider the ranges of intervention effects and contamination potential between trial arms when designing buffer areas.

PMID:40490768 | DOI:10.1186/s12936-025-05438-y

Confl Health. 2025 Jun 10;19(1):33. doi: 10.1186/s13031-025-00651-7.

ABSTRACT

BACKGROUND: People in war-affected and politically violent areas often experience traumatic events that can lead to long-lasting physical and mental health issues. This study aimed to assess the prevalence of post-traumatic stress disorder (PTSD), identify associated risk factors, and examine its relationship with the quality of life.

METHOD: A community-based cross-sectional study was conducted Between April 1 and May 15, 2022, in 812 individuals living in war-affected districts of the North Shewa Zone, Amhara Region, Ethiopia. A multistage sampling technique was employed to select the study subjects. Sociodemographic and pre-existing illness data were collected through face-to-face interviews using a pre-tested instrument. The Post-Traumatic Stress Disorder Checklist (PCL-5) was used to measure the PTSD symptoms and cut-off above 33 was used to identify individuals with PTSD. Health-related quality of life was measured using the World Health Organization’s (WHO) Quality of Life-brief version (WHOQOL-BREF) questionnaire. Binary logistic regression analysis was used to identify PTSD associated factors, while the independent T-test was applied to compare the quality of life (QOL). The model’s fit was evaluated using the Hosmer-Lemeshow goodness-of-fit test and a p-value of 0.05 was considered statistically significant.

RESULT: The prevalence of PTSD was 42.4%. Khat use (AOR = 2.33, 95% CI: 1.33-4.07, p < 0.001), having friends or family who died from mental illness (AOR = 3.91, 95% CI: 1.66-9.20, p < 0.01), conflicts with family, friends or loved ones (AOR = 1.89, 95% CI: 1.18-3.01, p < 0.01), poor social support (AOR = 3.84, 95% CI: 2.53-5.81, p < 0.001), and being coerced into accepting ideas against their will (AOR = 2.04, 95% CI: 1.37-3.03, p < 0.001) were significant factors associated with PTSD. Further, quality of life (QOL) was significantly lower by 0.87 points among individuals with PTSD compared to those without PTSD (t-value = 12.279, p < 0.001).

CONCLUSION: About 4 in 10 individuals living in war-affected districts of the North Shewa Zone, Amhara Region experienced PTSD. Avoiding substance use (a negative coping style) and providing psychotherapy that can adequately addresses the community’s medical, social, and psychological needs is essential for improving QOL in war-related PTSD.

PMID:40490765 | DOI:10.1186/s13031-025-00651-7