Category: Statistics

World J Microbiol Biotechnol. 2026 May 8;42(6):267. doi: 10.1007/s11274-026-05002-z.

ABSTRACT

The safety of live probiotics remains debated due to concerns regarding their viability and functional efficacy under harsh in vivo and in vitro conditions. Inflammatory bowel disease (IBD) is a complex disease stemming from various factors. It has been reported that probiotics shows anti-inflammatory function. This study evaluated the immunomodulatory and anti-inflammatory properties of heat-killed Lactobacillus strains (a form of postbiotics). Because viable Loigolactobacillus coryniformis NA-3 exhibited lower in vitro viability than Lactiplantibacillus plantarum NA, we first evaluated the phagocytic activity and TLR2-mediated immunoregulatory effects of heat-killed L. coryniformis NA-3 in RAW 264.7 cells, and conducted a preliminary comparative assessment of both live and heat-killed L. coryniformis NA-3 in murine models. We further investigated two distinct heat-killed strains: L. coryniformis NA-3 and Lactiplantibacillus plantarum NA. Heat-killed L. coryniformis NA-3 induced TLR2-dependent immunomodulatory effects in vitro and showed effects comparable to those of its live counterpart in vivo under the conditions tested. Both heat-killed strains were associated with changes in inflammatory markers, including decreased levels of pro-inflammatory cytokines (IL-6, TNF-α) and increased levels of anti-inflammatory mediators (IL-4, IL-10, TGF-β) in mice. In addition, they were associated with alterations in antioxidant parameters, including changes in SOD, GSH-Px, GR, NQO1, HO-1, Nrf2, and MDA levels, as well as increased expression of the tight junction proteins claudin-1 and occluding. Observations from this study are consistent with the potential involvement of the TLR2/NF-κB p65 signaling pathway. These findings highlight the potential of heat-killed probiotics as safe and effective alternatives to live strains in immune regulation and anti-inflammation.

PMID:42101791 | DOI:10.1007/s11274-026-05002-z

Jpn J Ophthalmol. 2026 May 8. doi: 10.1007/s10384-026-01362-z. Online ahead of print.

ABSTRACT

PURPOSE: To compare physician-assessed and patient-reported outcomes quantified with the Japanese Ocular Surface Disease Index (J-OSDI) following the treatment of bacterial blepharitis and to evaluate the utility of the J-OSDI.

STUDY DESIGN: Multicenter prospective observational study.

METHODS: Physicians assessed symptoms and findings, calculating clinical total scores at baseline (T0), 7 (T1) and 14 (T2) days post-treatment with 1% azithromycin ophthalmic solution, and 1 month after discontinuation (T3). Patients self-reported symptoms using the J-OSDI at these times. The J-OSDI score trends and differences in temporal changes between the J-OSDI and clinical total scores were analyzed by use of a linear mixed-effects model.

RESULTS: Forty-six eyes (46 patients; mean age, 71.8 years) were studied. The J-OSDI scores decreased significantly post-treatment for all the patients, with similar trends for both anterior and posterior blepharitis. For all the patients, the slope difference between the J-OSDI and clinical total scores was not significant in the T0-T1 period (P = .219), meaning that the J-OSDI scores reflected the clinical results, whereas it was significant in the T1-T2 (P = .004) and T2-T3 (P <.001) periods. The within-subject correlation between the 2 scores was 0.525 (95% CI 0.401-0.631). For anterior blepharitis, the slope differences were significant across all the periods, but for posterior blepharitis, no significant differences were observed in the T0-T1 or T1-T2 (P = .205, 0.06, respectively) periods, although significant differences were noted in the T2-T3 period (P = .018).

CONCLUSION: The J-OSDI trajectory often diverges from physician-rated changes. Whilst the J-OSDI does not assess treatment response in anterior blepharitis, it may be partially reflective of improvement in posterior blepharitis.

PMID:42101788 | DOI:10.1007/s10384-026-01362-z

Infection. 2026 May 8. doi: 10.1007/s15010-026-02807-w. Online ahead of print.

ABSTRACT

BACKGROUND: Praziquantel (PZQ) is the mainstay treatment for schistosomiasis, but its efficacy against juvenile schistosomes is limited, which can lead to treatment failure and reinfection. Artemisinin derivatives (ARTs) exhibit potent activity against juvenile worms, offering a complementary mechanism. However, the potential risk of accelerating artemisinin resistance, particularly in schistosomiasis-malaria co-endemic regions, warrants consideration when evaluating ART-based regimens. To find a more optimal regimen for the treatment of schistosomiasis, this meta-analysis evaluated the effectiveness of ARTs and PZQ in combination or as a single agent for the treatment of schistosomiasis.

PURPOSE: To evaluate the efficacy and safety of PZQ combined with ARTs compared with praziquantel alone for the treatment of schistosomiasis through a meta-analysis of randomized controlled trials.

METHODS: Randomized controlled trials (RCTs) of artemisinin derivatives in combination with praziquantel in the treatment of schistosomiasis were selected from computerized searches of PubMed, Embase, Cochrane Library, and Web of Science, up to November 2025. The inclusion criteria were randomized controlled trials involving participants diagnosed with Schistosoma mansoni, S. haematobium, or S. japonicum, who were treated with PZQ combined with ARTs or PZQ alone, and reporting on efficacy and safety outcomes. The primary outcome indicator was cure rate (CR), and secondary outcome indicators were egg count reduction rate and number of adverse events. The meta-analysis was performed using a random-effects model. Subgroup analyses were conducted to explore the impact of different types of schistosomes.

RESULTS: A total of eight studies, involving 1595 patients with schistosomiasis, explored the cure rate of PZQ combined with ARTs and PZQ alone. The pooled result showed that PZQ combined with ARTs had a significantly higher cure rate than PZQ alone (RR 1.12; 95% CI 1.01-1.24; P = 0.02). The corresponding subgroup analysis results showed that the CR of patients with S. mansoni treated with PZQ combined with ARTs was still higher than that of patients treated with PZQ alone (RR 1.16; 95% CI 1.01-1.34; P = 0.03). However, there was no statistically significant difference between PZQ combined with ARTs and PZQ for S. haematobium (RR 1.11; 95% CI 0.99-1.23; P = 0.06) or S. japonicum (RR 1.02; 95% CI 0.95-1.09; P = 0.60) in subgroup analyses. In addition, our study also found that there was no significant difference in egg count reduction between the PZQ-ARTs and PZQ-alone groups, either for S. mansoni (MD – 4.54, 95% CI – 17.67 to 8.58; P = 0.50) or for S. haematobium (MD – 13.74; 95% CI – 55.64 to 28.15; P = 0.52). Furthermore, the combination therapy was associated with a higher incidence of adverse events compared with PZQ alone (RR 1.41; 95% CI 1.01 to 1.96; P = 0.04).

CONCLUSIONS: The combination of PZQ and ARTs can significantly improve the CR for S. mansoni, but not for other schistosome species, at the cost of a higher incidence of adverse events, which were however manageable.

PMID:42101772 | DOI:10.1007/s15010-026-02807-w

Ir J Med Sci. 2026 May 8. doi: 10.1007/s11845-026-04424-w. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: Less is known about backward walking speed (BWS) in older adults. This study aims to establish a cutoff value for BWS to distinguish cognitively impaired individuals from healthy controls and to assess the association between backward walking slowing and risk of neurodegenerative diseases.

METHODS: 389 older patients, grouped into cognitively healthy (CH), amnestic mild cognitive impairment (aMCI), Alzheimer’s disease (AD), Parkinson’s disease (PD), and non-AD groups. BWS was measured using a standardized 4-meter protocol. Cognitive and functional status were evaluated via the comprehensive geriatric assessment. ROC analysis was used to determine the diagnostic threshold for BWS, and multinomial logistic regression was used to assess the associations.

RESULTS: A BWS cutoff of 0.395 m/s effectively distinguished CH individuals from those with neurodegenerative diseases (AUC=0.723). After adjusting for age, each 0.1 m/s decrease in BWS was associated with 22% increased odds of having aMCI, 37% increased odds of AD, 28% increased odds of PD, and 59% increased odds of having non-AD dementia. BWS showed a positive association with global cognitive scores in patients with CH and aMCI (p< 0.05) and with semantic verbal fluency scores in those with AD and aMCI (p< 0.05).

CONCLUSION: BWS is associated with an increased risk of neurodegenerative diseases, which can cause cognitive impairment, and may help indicate individuals at risk of cognitive decline.

PMID:42101771 | DOI:10.1007/s11845-026-04424-w

Psicol Reflex Crit. 2026 May 8. doi: 10.1186/s41155-026-00392-3. Online ahead of print.

ABSTRACT

INTRODUCTION: During the COVID-19 pandemic, rates of loneliness increased significantly due to the challenging and adverse context arising from this global health emergency.

OBJECTIVE: To classify adults living alone according to perceived loneliness and affectivity and to examine their association with symptoms of psychological distress during the COVID-19 pandemic.

METHOD: The design of this study was cross-sectional, descriptive and correlational. The sample consisted of 418 adults living alone, recruited through a non-probabilistic snowball sampling procedure using an online survey distributed via social media and email. To analyze the data, a cluster analysis was applied using the k-means method, the chi-squared test and the Odds Ratio statistic.

RESULTS: Two homogeneous groups were identified: Group 1 (n = 233) characterized by high levels of perceived loneliness, low levels of positive affect and high levels of negative affect; Group 2 (n = 185) showed low levels of perceived loneliness, high levels of positive affect and low levels of negative affect. Cluster 1 was more likely to have symptoms of psychological distress than cluster 2.

CONCLUSIONS: To summarize, loneliness among individuals who reside alone can have an impact on the likelihood of experiencing psychological distress and adverse effects.

PMID:42101766 | DOI:10.1186/s41155-026-00392-3

Prev Sci. 2026 May 8. doi: 10.1007/s11121-026-01911-5. Online ahead of print.

ABSTRACT

Artificial intelligence (AI)-powered computational methods, such as machine learning and natural language processing, are increasingly applied in deaths of despair research among Indigenous populations. However, their application in Indigenous contexts is often constrained by epistemological misalignment, technical limitations, and ethical concerns. Integrating Indigenous Research Methodologies into AI-powered prevention science research is necessary to support Indigenous Data Sovereignty and address deaths of despair. The Indigenous Computational Approach (ICA) provides a structured reflexive protocol for constructing Indigenous Statistical Spaces that operationalize Indigenous Research Methodologies within computational workflows. ICA aligns four interdependent components: Researcher Standpoint, Indigenous Theoretical Frameworks, AI Data Analysis Technique, and Dissemination and Indigenous Governance. This protocol is supported by operational steps and an accompanying ICA Checklist. A previously published case study on the Indigenous Wholistic Factors Project illustrates the ICA in practice in the context of suicide risk modeling. The case study applied a lasso logistic regression model to structure feature selection on an Indigenous subsample of the 2019-2020 California Healthy Kids Survey (n = 2609). Ten of 17 candidate features were retained, and the model demonstrated strong discrimination (AUC = 0.87) and acceptable calibration (Brier score = 0.10). The ICA does not guarantee different empirical findings or superior model accuracy, but rather it restructures how AI models are designed, validated, and deployed for prevention science research. The ICA provides a replicable protocol for AI-powered prevention science research to support Indigenous self-determination and community-defined well-being.

PMID:42101761 | DOI:10.1007/s11121-026-01911-5

Saudi Dent J. 2026 May 8;38(5):64. doi: 10.1007/s44445-026-00158-8.

ABSTRACT

When it comes to root canal therapy, the right working length (WL) must be established in order to minimize material extrusion and the resulting post- procedure pain. Although electronic apex locators (EALs) are a radiation-free, time-saving substitute for conventional or digital radiography techniques, but their impact on postoperative pain has been controversial. This systematic review was registered in PROSPERO (CRD420251247626) and adhered to PRISMA 2020 guidelines. Randomized controlled trials (RCTs) comparing EAL versus radiographic WL determination, with postoperative pain as an outcome, were searched in PubMed, Cochrane CENTRAL, and ScienceDirect from January 2000 to November 17, 2025. Only peer-reviewed RCTs involving permanent teeth were considered. Bias risk was evaluated using Cochrane RoB 2.0. Four RCTs (total n = 414 patients) met the inclusion criteria. Four RCTs (2014-2024) showed no statistically significant difference in postoperative pain incidence, intensity (measured by VAS or 4-point verbal rating scale), analgesic consumption, or time to pain resolution between EAL and radiographic groups at any time point (4 h to 7 days). Pain levels were generally low to moderate and resolved within 72 h in both groups. One three-arm trial demonstrated significantly lower early pain (6-48 h) with a simultaneous/hybrid EAL plus radiographic technique compared with either method alone. No flare-ups or serious adverse events were reported. Based on limited evidence from four RCTs with methodological concerns (including risks in randomization, blinding, and subjective pain assessment) and very low certainty, electronic apex locators and radiographic methods may yield similar postoperative pain outcomes in single-visit root canal treatment of vital teeth. A combined method of both techniques showed preliminary indications of early pain alleviation in one small trial on symptomatic conditions, but this requires confirmation. EALs may represent a radiation free alternative or supplement to radiography that does not appear to increase pain, though the evidence is insufficient to draw firm conclusions.

PMID:42101759 | DOI:10.1007/s44445-026-00158-8

Acta Neuropsychiatr. 2026 May 8:1-55. doi: 10.1017/neu.2026.10085. Online ahead of print.

ABSTRACT

OBJECTIVE: Dementia is a group of symptoms, characterized by a loss of cognition that interferes with everyday tasks, difficulty focusing, planning, problem solving, and behavioral changes, such as apathy, anxiety, or depression. The leading cause of dementia is Alzheimer’s disease, but vascular dementia or mild cognitive impairment are also frequently occurring. There are six drugs legislated in Europe for use in the treatment of dementia. There are unmet clinical needs to find more effective, better tolerated or complementary therapeutic options. The aim of this study is to comprehensively analyze the results of clinical trials and other human studies regarding the efficacy and safety of herbal interventions used in patients with dementia.

METHODS: We enrolled a total of 48 studies for this systematic review, of which 27 were included into the statistical analysis of effect size (Cohen’s d).

RESULTS: We found significant improvements mainly after administration of Ginkgo biloba, Crocus sativus, Salvia officinalis, and Melissa officinalis.It should be emphasized that some herbs and herbal formulations demonstrated efficacy comparable to that of donepezil, a widely used and approved medication, suggesting potential for phytopharmaceutical therapies as complementary approaches. In some studies, the observed effects were similar to those reported for conventional treatments, indicating promising directions for further research in Alzheimer’s disease and dementia.

CONCLUSION: In light of the evidence, phytopharmaceuticals have a promising role as a co-therapeutic option or alternative for patients with dementia who do not tolerate or have contraindications to standard medications. However, further research is necessary to translate these initial promising results into clinical practice.

SUMMATIONS: Phytopharmaceuticals have a promising role as a complementary or alternative option for dementia patients who cannot tolerate or respond to standard medications. Certain phytopharmaceuticals demonstrated comparable short-term symptomatic effects to standard treatments in small trials; however, evidence is insufficient to support equivalence or superiority.

CONSIDERATIONS: Many of the studies reviewed are limited by very small sample sizes, which is associated with a high risk of bias when interpreting large effect sizes (Cohen’s d). The short duration of interventions (often only 3 to 6 months) is insufficient to assess whether phytotherapeutics can constitute disease-modifying treatments (DMTs).

PMID:42100836 | DOI:10.1017/neu.2026.10085

Psychol Med. 2026 May 8;56:e123. doi: 10.1017/S0033291726103833.

ABSTRACT

BACKGROUND: Systemic inflammation is hypothesized to contribute to post-traumatic stress disorder (PTSD) vulnerability. Few studies have examined inflammation shortly after trauma as a predictor of later PTSD symptoms. We examined whether inflammation from the emergency department (ED) post-trauma is associated with PTSD symptom severity over the following 6 months.

METHODS: Our sample included 742 AURORA participants, a longitudinal cohort of patients in 29 EDs across the United States after a traumatic stressor, followed up to 6 months. Plasma cytokines were assessed from a study blood draw in the ED: an inflammatory index (standardized sum of generally pro-inflammatory markers interleukin [IL]-6, IL-8, tumor necrosis factor alpha [TNF-α], interferon gamma [IFN-γ]), and generally anti-inflammatory IL-10. PTSD symptoms were self-reported at 2 weeks, 8 weeks, 3 months, and 6 months post-ED. Covariate-adjusted repeated-measures regressions estimated associations between inflammation and PTSD symptoms, overall and sex-stratified.

RESULTS: Among 742 participants (age m = 40.0 [13.7]; 479 [64.6%] female), PTSD symptoms were elevated then modestly decreased over follow-up. Higher ED inflammation was associated with higher PTSD symptoms across follow-up (standardized symptoms β = 0.05, 95% CI: 0.01-0.09), adjusted for potential confounders. Higher pro-inflammatory index levels and IL-6, IL-8, and TNF-α were associated with higher PTSD symptoms in males only, while higher IL-10 was associated with higher PTSD symptoms in females only.

CONCLUSIONS: Pro-inflammatory levels shortly after traumatic stress are associated with heightened PTSD symptoms, particularly among males. Inflammatory markers may prove useful additions to prediction models for PTSD following trauma, with attention to sex differences.

PMID:42100824 | DOI:10.1017/S0033291726103833

Stroke. 2026 May 8. doi: 10.1161/STROKEAHA.126.055315. Online ahead of print.

ABSTRACT

BACKGROUND: Preservation of treatment allocation randomness, achievement of treatment group size balance, and balance on prognostic baseline covariates are desirable properties of optimal randomization schemes. Previous studies have demonstrated the accuracy of covariate-adaptive randomizations, such as minimal sufficient balance (MSB) randomization, for achieving covariate balance in acute stroke trials at the end of the trial. This study evaluates the performance of covariate-adaptive randomization techniques against simple and block randomization in minimizing site-specific treatment group imbalance in multicenter acute stroke trials.

METHODS: Monte Carlo simulations were used to evaluate the performance of stratified and unstratified versions of MSB, common scale MSB, and common scale group-size MSB (CSSize-MSB), against permuted block and simple randomization designs, for achieving balance across baseline covariates and sites. Simulation conditions investigated include the number of sites (3, 6, or 20 sites), enrollment per site (equal or unequal enrollment across sites), number and distribution of baseline covariates (sex, age, National Institutes of Health Stroke Scale score, large vessel occlusion status), and sample size (n=250, 600, 1000, 3000). The probability of observing statistically significant imbalance on any baseline covariate, proportion of biased allocations, and overall and site-specific group allocation ratio at interims and end of enrollment were used to evaluate the performance of the randomization schemes.

RESULTS: The average probability of observing imbalance on any of the baseline covariates for the simple randomization, permuted block, common scale MSB, common scale group-size MSB, and MSB were 21%, 21%, 0%, 2%, and 2%, respectively, at n=600 with 20 study sites. Although site-specific treatment allocation imbalance was improved under MSB algorithms, imbalance at low-enrolling sites persisted, regardless of the randomization scheme. Treatment allocation randomness and treatment-control group balance were preserved in high-volume sites under MSB.

CONCLUSIONS: Although site-specific treatment group imbalance persisted in low-enrolling sites, regardless of the randomization technique adopted, the overall randomness of treatment allocation and balance of covariates were preserved with MSB algorithms. Logistical considerations and oversight to minimize low enrollment across sites are recommended before onboarding sites in multicenter acute stroke trials.

PMID:42100801 | DOI:10.1161/STROKEAHA.126.055315