Category: Statistics

Arch Oral Biol. 2025 Oct 24;181:106422. doi: 10.1016/j.archoralbio.2025.106422. Online ahead of print.

ABSTRACT

AIM: The aim of this study was to assess the dose-dependent effects of radiotherapy on the progression of apical periodontitis (AP) in rats.

METHODS: Forty-five animals were divided into five groups based on radiation dose and apical periodontitis induction (n = 9): AP-RT7 (irradiated with a dose of 7.5 Gy + AP); AP-RT10 (10 Gy dose + AP); AP-RT15 (15 Gy dose + AP); AP (AP without radiation), and Control (no intervention). Radiation therapy was administered on the first day of the experiment. After seven days, the apical periodontitis induction was carried out in all groups except Control. All animals were euthanized after 21 days of AP progression (day 28), and the area and volume of AP were analyzed using radiography, micro-CT, and histological analyses. Inflammation intensity and extent were assessed histologically. Statistical analysis was performed using ANOVA and Student’s t test for quantitative data, and Kruskal-Wallis for ordinal data (P < 0.05).

RESULTS: The AP-RT15 group exhibited significantly larger apical periodontitis lesions compared to the AP-RT7.5, AP-RT10, and AP groups, as demonstrated by radiographic (p < 0.05), micro-CT (p < 0.0001), and histological analyses (p < 0.0001). Histological examination further revealed a more extensive and intense inflammatory response in the AP-RT15 group (p < 0.01). Overall, radiotherapy contributed to increased apical bone resorption and exacerbated inflammation in a dose-dependent manner.

CONCLUSIONS: The progression of apical periodontitis in irradiated animals follows a dose-dependent pattern, with higher radiation doses markedly amplifying the lesion’s area, volume, and inflammatory severity.

PMID:41187381 | DOI:10.1016/j.archoralbio.2025.106422

Arch Oral Biol. 2025 Oct 28;181:106443. doi: 10.1016/j.archoralbio.2025.106443. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to investigate the effect of the periodontal bacterium Filifactor alocis on proinflammatory cytokine production by osteoblasts. Specifically, we examined the mechanisms underlying interleukin (IL)-6 production by osteoblasts stimulated with live and lyophilized F. alocis, and F. alocis-derived extracellular vesicles (EVs).

DESIGN: MC3T3-E1 mouse osteoblasts were stimulated with live bacteria of F. alocis and, as a comparative control, P. gingivalis. Furthermore, cells were treated with F. alocis lyophilized whole cells or EVs, and IL-6 production was quantified by ELISA; cytokine expression profiled using membrane-based array; and mRNA expression analyzed by RT-qPCR. Signaling pathways were analyzed using specific inhibitors. Statistical analyses were performed using non-parametric tests with significance set at p < 0.05.

RESULTS: F. alocis live bacteria, lyophilized whole cells, and F. alocis-derived EVs induced IL-6, leukemia inhibitory factor, and chemokines in MC3T3-E1 cells. Mechanistically, IL-6 production by F. alocis involved osteoblast activation via Toll-like receptor (TLR) 2 on the bacterial surface or released EVs. Lyophilized F. alocis induced IκB-ζ mRNA expression in osteoblasts. Moreover, F. alocis-derived EVs induced IL-6 production in osteoblasts via protein kinase C (PKC).

CONCLUSIONS: Live and lyophilized F. alocis and F. alocis-derived EVs induce the production of proinflammatory cytokines by osteoblasts, including IL-6. Additionally, the induction of IL-6 by F. alocis-derived EVs involves the activation of TLR2 and PKC. Conclusively, these findings suggest that F. alocis-induced cytokine production by osteoblasts may induce osteoclast differentiation, highlighting its role in the pathogenesis of periodontitis.

PMID:41187379 | DOI:10.1016/j.archoralbio.2025.106443

Prev Vet Med. 2025 Oct 31;246:106734. doi: 10.1016/j.prevetmed.2025.106734. Online ahead of print.

ABSTRACT

Infectious bronchitis virus (IBV) remains a major respiratory pathogen of economic concern in the poultry industry. This study investigated the farm-level prevalence of IBV and evaluated associated risk factors in northern Vietnam by a cross-sectional study from June 2022 to June 2024. A total of 69 poultry farms were randomly selected across nine provinces, and pooled tracheal swab samples were purposively collected for IBV detection using RT-qPCR. The overall IBV farm-level prevalence was 34.78 % (95 % CI:23.71-47.21 %). Although no statistically significant differences were found across provinces, production types, age groups, or flock sizes, IBV was detected in all subgroups, indicating widespread circulation of the virus. A total of 22 potential risk factors were initially assessed using univariate logistic regression. Of these, six variables with P < 0.1, including farm size, number of poultry houses, presence of multiple age groups, vaccination at day-old, frequency of disinfection before chick placement, and proximity to live bird markets and residential areas, were selected for multivariable logistic regression. The final multivariable model retained two independent predictors: performing more than one disinfection before chick placement (P = 0.035), and administration of a live IB vaccine at one day of age (P = 0.006), both of which were significantly associated with reduced the odds of IBV infection at the farm level. These findings suggest that strategic vaccination and careful calibration of disinfection protocols are critical to minimizing IBV transmission at the farm level.

PMID:41187363 | DOI:10.1016/j.prevetmed.2025.106734

J Radiol Prot. 2025 Nov 4. doi: 10.1088/1361-6498/ae1b15. Online ahead of print.

ABSTRACT

Epidemiological studies of large groups of nuclear industry workers offer a significant opportunity to increase our understanding of the long-term effects on health of the protracted accumulation of dose received at a low dose rate from many discrete exposures to ionising radiation. The effects of such extended aggregation of doses form an important part of the everyday concerns of radiological protection against low-level exposures. For more than half a century, databases of nuclear workers have been assembled, and the numbers of workers currently included in studies, together with the numbers of deaths among them that have now occurred, are capable of generating reasonably precise risk estimates that should provide meaningful comparisons with those obtained from other studies, such as of the Japanese atomic bomb survivors. However, constructing, updating and maintaining these large databases, linking workers to occupational dose databases and to registers of deaths (and other outcomes, such as incident cancers) and their causes, and analyses of these data that endeavour to take account of other influential factors (such as smoking) are far from straightforward. A critical review of recent nuclear worker studies illustrates the difficulties in reliably interpreting reported statistical associations between rates of cancer and cumulative occupational doses because of the real possibility of distortions produced by biases, confounding and/or the interplay of radiation with other risk factors. This doesn’t mean that studies of nuclear workers should be abandoned, far from it, but it does mean that appropriate effort needs to be expended on these studies before confident conclusions about the levels of risks from radiation exposure can be drawn from them. Unexpected findings should be examined in depth to gain a proper understanding of their origin, including the impact of doses from intakes of radionuclides upon dose-responses derived using doses from external sources of radiation.

PMID:41187351 | DOI:10.1088/1361-6498/ae1b15

Am J Trop Med Hyg. 2025 Nov 4:tpmd240812. doi: 10.4269/ajtmh.24-0812. Online ahead of print.

ABSTRACT

The efficacy, best dosage, and safety of liposomal amphotericin B (LAB) in the treatment of cutaneous leishmaniasis (CL) caused by Leishmania braziliensis in elderly patients was determined by a randomized, controlled trial. We selected 28 patients of both sexes age 60 years old or older with CL diagnosis confirmed by detection of L. braziliensis DNA. The groups were treated with different total doses of LAB (group 1: 12 mg/kg; group 2: 18 mg/kg; and group 3: 24 mg/kg). Clinical and laboratory evaluations were carried out during a period of 180 days (day 0, day 15, day 30, day 60, day 90, and day 180). The highest cure rate (89%) was in group 3 (differences were not statistically significant) along with the lowest incidence of side effects (11%), suggesting that 24 mg/kg is the best dose of LAB to treat CL in elderly patients.

PMID:41187344 | DOI:10.4269/ajtmh.24-0812

Am J Trop Med Hyg. 2025 Nov 4:tpmd250483. doi: 10.4269/ajtmh.25-0483. Online ahead of print.

ABSTRACT

The objective of this study was to compare coronavirus disease 2019 (COVID-19) and influenza among US active-component service members (ACSMs) stationed at military installations near the US-Mexico border (Arizona, California, New Mexico, and Texas). A retrospective cohort study was conducted to assess diagnoses of influenza (2020-2024) and COVID-19 (2020-2023). Incidence rate ratios (IRRs) comparing influenza and COVID-19 at border and non-border locations were calculated for laboratory-confirmed and/or symptom-based encounter diagnoses. Forty-five percent of ACSMs included in the influenza (N = 650,505) and COVID-19 (N = 660,333) analyses were near the border. There was no statistically significant increase of either COVID-19 or influenza incidence among ACSMs stationed near the border compared with those located elsewhere in the same states. A statistically significantly reduced adjusted IRR (aIRR) of laboratory-confirmed influenza (aIRR: 0.93; 95% CI: 0.89, 0.98) and COVID-19 (aIRR: 0.97; 95%: CI: 0.96, 0.99) was observed among ACSMs stationed near the border compared with those located elsewhere in the same states for all states combined for the entire study period. Similarly, significantly lower aIRRs were observed for all diagnoses (laboratory-confirmed or symptoms-based encounter) of influenza (aIRR: 0.81; 95% CI:0.80, 0.82) among ACSMs near the border compared with ACSMs not near the border for all states combined for the entire duration of the study. However, incidence rates of COVID-19 and influenza varied across some specific states and time periods. By assessing the potential health threats of cross-border transmission, public health officials can more effectively deploy preventive and response measures among ACSMs living and working near the US-Mexico border.

PMID:41187337 | DOI:10.4269/ajtmh.25-0483

ACS Chem Biol. 2025 Nov 4. doi: 10.1021/acschembio.5c00715. Online ahead of print.

ABSTRACT

Hexokinase domain containing protein 1 (HKDC1) is a recently discovered fifth human hexokinase isozyme that is significantly upregulated in several disease states, including lung and liver cancers. Cellular studies suggest that HKDC1 is a low activity hexokinase; however, its functional characteristics have remained enigmatic. Here, we describe the kinetic and regulatory features of recombinant human HKDC1, demonstrating it to be a robust hexokinase (k_cat/K_m,glucose = 1.5 × 10⁴ M^-1 s^-1) with a unique glucose K_m value (0.49 ± 0.07 mM) that differs markedly from all other human hexokinase isozymes. The isolated C-terminal domain of HKDC1 displays kinetic characteristics nearly identical to the full-length enzyme, whereas the N-terminal domain is inactive. Unlike all other 100 kDa vertebrate hexokinases characterized to date, HKDC1 is insensitive to product inhibition by physiological concentrations of glucose 6-phosphate, with apparent inhibition constants above 1 mM. The hexokinase activity of HKDC1 is also insensitive to Dinaciclib, a pan cyclin-dependent kinase inhibitor that reportedly disrupts the ability of nuclear localized HKDC1 to phosphorylate retinoblastoma-binding protein 5. Conversely, the hexokinase activity of HKDC1 is potently inhibited by a synthetic glucosamine derivative previously developed for hexokinase 1 and 2, with an IC₅₀ value of 103 ± 6 nM. An HKDC1 variant associated with retinitis pigmentosa, T58M, displays a modest, but statistically significant 2-fold decrease in catalytic efficiency (k_cat/K_m,glucose) compared to the wild-type enzyme. Together, our results provide a detailed functional characterization of recombinant HKDC1 and set the stage for investigating the link between HKDC1 catalysis and human disease.

PMID:41187334 | DOI:10.1021/acschembio.5c00715

Arch Cardiol Mex. 2025 Nov 4. doi: 10.24875/ACM.25000124. Online ahead of print.

ABSTRACT

The objective of this study was to evaluate the efficacy of percutaneous left atrial appendage occlusion (LAAO) compared with anticoagulation in patients with atrial fibrillation (AF) and its impact on the primary prevention of ischemic stroke and all-cause mortality. Patients with non-valvular AF and high thromboembolic risk (CHA₂DS₂-VASc > 2 points) were included. LAAO was compared against the use of direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs). Articles were searched in PubMed, Scopus, and Web of Science up to June 11, 2025. Risk of bias was assessed using the RoB 2 tool and ROBINS-E, while statistical analysis was performed with Review Manager 5.4.1. A total of 10 studies with 5,779 patients were analyzed (2,916 with LAAO and 2,863 with anticoagulation). LAAO reduced, though without statistical significance, the incidence of ischemic stroke (OR: 0.82; 95% CI: 0.66-1.03; p = 0.09). However, it showed a significant reduction in all-cause mortality compared with the overall anticoagulant group (OR: 0.62; 95% CI: 0.46-0.80; p = 0.0004). LAAO emerges as a viable strategy to reduce mortality in patients with AF and high thromboembolic risk, particularly when long-term anticoagulation is not feasible. Its superiority over DOACs and comparable profile to VKAs, along with the absence of periodic INR monitoring and relevant drug interactions, make it an option that may optimize adherence and quality of life.

PMID:41187332 | DOI:10.24875/ACM.25000124

J Med Internet Res. 2025 Nov 4;27:e63816. doi: 10.2196/63816.

ABSTRACT

BACKGROUND: Patient interaction patterns with self-triage modules in mobile health apps during urgent direct-to-consumer telemedicine consultations remain underexplored, despite their critical role in optimizing virtual care pathways.

OBJECTIVE: This study aimed to analyze user navigation behaviors within the screen pathways of a symptom-based self-triage mobile app’s algorithm during remote urgent care assessments.

METHODS: This observational, retrospective, single-center study analyzed data from users who were aged 18 years and older and who voluntarily sought virtual urgent care through the Einstein Conecta (version 2.0; iOS and Android) at a private Brazilian hospital between May 2022 and December 2023. Patients with incomplete connection records were excluded. User interactions were evaluated based on the number of distinct triage flows accessed per session, the number of screens viewed per flow, the frequency of returns to previous screens, and the time spent within the self-triage module. Descriptive statistical methods were applied for analysis.

RESULTS: Data from 62,006 unique users with a mean age of 36.51 (SD 10.53) years, of whom 54.65% (33,889/62,006) were female, were analyzed. They initiated 194,976 self-triage flows. We found that 36.89% (22,875/62,006) of users completed 1 flow per session; 22.15% (13,734/62,006) users accessed 2 flows; and 27.93% (17,317/62,006) users accessed ≥4 flows (maximum 63 flows). Users receiving an initial emergency department referral recommendation were more likely to initiate subsequent flows than those recommended for virtual assessment. Returning to a previous screen was infrequent (used by 5277/62,006, 8% of users). The average time spent in the first flow was 70.95 (SD 65.26) seconds, with an average of 9.51 (SD 12.84) seconds per screen.

CONCLUSIONS: In this cohort, most users explored alternative pathways beyond the initial self-triage recommendation, particularly when directed to the emergency department, while rarely backtracking within a flow. These findings underscore the need to refine self-triage mechanisms in telemedicine to better align with observed user navigation behaviors and preferences.

PMID:41187328 | DOI:10.2196/63816

JMIR Res Protoc. 2025 Nov 4;14:e78806. doi: 10.2196/78806.

ABSTRACT

BACKGROUND: Neuropathic pain (NP) is characterized as pain arising from lesions of the somatosensory nervous system. However, NP-like features have been found in several chronic secondary musculoskeletal (MSK) pain conditions in the absence of detectable lesion or damage to the somatosensory pathways. Emerging evidence has demonstrated associations between NP-like symptoms and altered neural activity within brain regions implicated in sensory perception and affective-emotional processing of pain with consistent findings of abnormal activity in the right insula (RIns) cortex and dorsal anterior cingulate cortex (dACC). Electroencephalography neurofeedback (EEG-NF) is a brain-computer interface biofeedback technique that allows individuals to self-regulate the real-time cortical brain activities of the regions of interest.

OBJECTIVE: The primary objective of this study is to investigate the feasibility and safety of a novel EEG-NF intervention designed to simultaneously downtrain activity in the RIns and dACC in individuals with a chronic secondary MSK pain condition exhibiting NP-like features. In addition, this study will conduct secondary exploratory analyses to investigate EEG-derived neuronal changes and their associations with clinical and experimental pain outcomes following the EEG-NF training.

METHODS: We will design a single-arm, open-label, pilot-feasibility trial. We will recruit adults aged 35-75 years with a score of ≥19 using the PainDETECT questionnaire and an average pain score of ≥4 on the 11-point Numeric Pain Rating Scale over the last 3 months, with a minimum pain duration of 3 months, to receive active EEG-NF training. Participants will receive auditory feedback as a reward for achieving a predetermined activity threshold of the RIns and dACC. Primary outcomes will evaluate feasibility, acceptability, and safety using both self-reported questionnaires and monitoring data. Collected data will be summarized descriptively, with mean (SD) reported where appropriate. Secondary outcomes will include EEG parameters, self-reported measures, heart rate variability, and quantitative sensory testing. An exploratory within-group pre-post statistical comparison will be conducted for all secondary outcome measures, and correlation analysis will be performed to explore relationships between EEG measures, self-reported outcomes, heart rate variability, and quantitative sensory testing measures.

RESULTS: This study has received approval from the Health and Disability Ethics Committee and is registered with the Australian New Zealand Clinical Trials Registry. Participant recruitment began in April 2025 and is ongoing. As of October 2025, data collection has been completed, with a total of 5 participants enrolled, all of whom have completed the study to date. We expect to complete the study in March 2026. This study will generate data on feasibility, safety, acceptability, and preliminary data to inform a fully powered effectiveness clinical trial.

CONCLUSIONS: The results and data generated will inform the design and sample size calculation for a fully powered randomized controlled trial aimed at evaluating the effectiveness of EEG-NF in targeting NP-like features in individuals with chronic MSK pain.

TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12625000706471; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=389568&isReview=true.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/78806.

PMID:41187327 | DOI:10.2196/78806