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Strengthening causal inference and analytical rigor in the Wumei Pills-Lactobacillus reuteri-intestinal stem cell axis for chemotherapy-induced mucositis

World J Stem Cells. 2026 Jan 26;18(1):114114. doi: 10.4252/wjsc.v18.i1.114114.

ABSTRACT

A recent preclinical study reported that Wumei Pills (WMP) and Lactobacillus reuteri (L. reuteri) mitigate 5-fluorouracil-induced intestinal mucositis by promoting intestinal stem cell (ISC)-mediated repair via Wnt/β-catenin signaling. The mechanistic interpretation rests largely on systemic inflammation readouts, correlative microbiota changes, and immunohistochemistry of pathway markers. From a clinical standpoint, chemotherapy-induced mucositis remains a common and burdensome toxicity that leads to dose reductions, treatment delays, and infection risk; current care is largely supportive and does not directly restore ISC-mediated repair. This unmet need motivates rigorous appraisal of the proposed “WMP → L. reuteri → ISC/Wnt” axis. To highlight key methodological considerations that may affect causal inference and analytical rigor in the proposed “WMP → L. reuteri → ISC/Wnt” pathway. This letter critically appraises the study’s design, endpoints, and analyses against current best practices in mucositis biology, microbiome causality testing, Wnt/β-catenin pathway validation, and preclinical statistics, and synthesizes concrete, literature-grounded remedies. Six issues with potential impact on interpretation were identified: (1) Reliance on serum cytokines/lipopolysaccharide to infer local mucosal inflammation, with limited tissue-level indices (e.g., myeloperoxidase, interleukin-1β, immune-cell infiltration); (2) Absence of necessity/sufficiency tests to verify microbiota mediation (e.g., L. reuteri depletion, WMP-donor fecal microbiota transplantation, probiotic add-back); (3) Pathway evidence tiering – Wnt/β-catenin activation not confirmed by β-catenin nuclear translocation or downstream targets (Axin2, c-Myc, cyclin D1), and Lgr5 quantification/specificity insufficient; (4) Statistical design under-specified (power justification, blinded assessment, control of multiple comparisons) and potential cage effects unmodeled; (5) Limited dose-response and safety profiling for WMP/L. reuteri; and (6) Constrained generalizability (single sex/strain/age, lack of ABX-only controls, single time-point). The reported benefits of WMP and L. reuteri in chemotherapy-induced mucositis are promising, but stronger causal and analytical foundations are needed. Incorporating tissue-level inflammation readouts, microbiota loss-/gain-of-function designs, definitive Wnt/β-catenin activation assays, rigorous statistical practices (including mixed-effects models for cage clustering and multiplicity control), dose-response/safety evaluation, and broader experimental scope (sex/age/strain, ABX-only controls, time-course) will yield more robust and translationally relevant conclusions.

PMID:41608653 | PMC:PMC12836234 | DOI:10.4252/wjsc.v18.i1.114114

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Association between single, dual, poly use of tobacco products and smoking cessation in Korean adult smokers

Tob Prev Cessat. 2026 Jan 27;12. doi: 10.18332/tpc/214782. eCollection 2026.

ABSTRACT

INTRODUCTION: This study examined the association between smoking cessation and different usage combinations of three tobacco products (combustible cigarette [CC], electronic cigarette [EC], heated tobacco product [HTP]) in Korean adults.

METHODS: We analyzed repeated data from the Korea Health Panel Survey (KHPS), which consisted of nationally representative samples. A total of 1380 Korean adults participated in the study. The outcome of interest was whether the participant succeeded in quitting smoking all types of tobacco products. Participants were classified according to whether they smoked any of the three tobacco products (CCs and/or ECs and/or HTPs) based on their self-reported responses.

RESULTS: A total of 211 participants had quit smoking during the follow-up period. After adjusting for potential confounding factors, the adjusted odds ratio (AOR) for smoking cessation was 3.15 (95% CI: 1.66-5.95), and 1.81 (95% CI: 0.63-5.21) for participants who currently smoke only HTPs (HTP-only user) and participants who currently vape only ECs (EC-only user), respectively, compared with participants who currently smoke only CCs (CC-only user). There was no significant association between dual or triple smoking and smoking cessation.

CONCLUSIONS: HTP-only users had a statistically significant association with smoking cessation, with higher odds of quitting smoking within two years compared to CC-only users. Further studies with a large sample are required to validate our results considering a small number of participants in the comparison groups in this study.

PMID:41608649 | PMC:PMC12838446 | DOI:10.18332/tpc/214782

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Effect of aquatic-treadmill training on cerebrovascular function and gait in community-dwelling stroke survivors: a feasibility and preliminary efficacy study

Front Sports Act Living. 2026 Jan 13;7:1680250. doi: 10.3389/fspor.2025.1680250. eCollection 2025.

ABSTRACT

BACKGROUND: Water-based exercise augments exercise-induced increases in brain blood flow, optimizing a proposed key mechanistic pathway for improved brain health. Aquatic treadmill exercise has been shown to aid gait re-education of stroke survivors, however its potential to enhance cerebrovascular function in this clinical population has not been tested. This pilot study aimed to examine the feasibility and preliminary efficacy of a 4-week aquatic treadmill (ATM) training intervention on cerebrovascular responsiveness and gait function in stroke survivors.

METHODS: Six community-dwelling stroke survivors (58 ± 11 years, 8 ± 11 years post stroke) completed a 4-week ATM intervention, consisting of 20-30 min sessions, 3 times/week. Pre- and post-intervention measures were taken of cerebrovascular reactivity (CVR), indexed via changes in middle cerebral artery blood velocity (MCAv) to a hypercapnic (5% CO2 in air) stimulus. Changes in mobility were assessed via 10-metre walk, Timed-Up-And-Go, and 6-minute walk (6MW) tests.

RESULTS: Adherence to the intervention was excellent, with 70 of the 72 (97%) available training sessions completed by participants. CVR increased on average by 44% (95% CI: ±58%; 2.8%-4.0%ΔMCAv/mm Hg ΔPETCO2) in the stroke-affected hemisphere and 48% (95% CI: ±41%; 3.0%-4.5%ΔMCAv/mm Hg ΔPETCO2) in the unaffected hemisphere post intervention, although changes did not reach statistical significance (p = 0.218; Friedman’s test). Within-group gait improvements were seen in speed and distance, with some changes above clinically meaningful thresholds; although this was not uniformly evident.

CONCLUSION: This pilot study established ATM training as a feasible option for some patients in stroke rehabilitation. Despite the limited sample size, the study demonstrated promising enhancements in cerebrovascular function, with preliminary evidence suggesting concurrent improvements in gait performance. Well-designed, larger studies are warranted.

PMID:41608538 | PMC:PMC12835293 | DOI:10.3389/fspor.2025.1680250

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Factors Associated with Delays in Breast Cancer Diagnosis in Low- and Middle-income Countries: A Scoping Review

Int J Community Based Nurs Midwifery. 2026 Jan 1;14(1):22-42. doi: 10.30476/ijcbnm.2025.104511.2632. eCollection 2026 Jan.

ABSTRACT

BACKGROUND: Delayed breast cancer diagnosis in low- and middle-income countries (LMICs) reduces the survival rates. This review identifies the causes of these delays to inform strategies for improving early detection.

METHODS: This scoping review followed the Arksey and O’Malley framework to explore the factors contributing to delayed breast cancer diagnosis in LMICs. Seven databases, including PubMed, Scopus, Web of Science, Cochrane Library, ProQuest, Embase, and Magiran, were searched for English and Persian studies published between January 2000 and September 2024. The search combined the keywords (e.g., “diagnostic delay,” “missed diagnosis,” “breast cancer,” “late-stage,” “barriers”), using Boolean operators. To focus on LMICs, we applied country filters, where available, and supplemented the search with manual screening of reference lists from the included studies.

RESULTS: The initial database search identified 5,313 records. After removing 1,036 duplicates, 4,277 studies were screened based on title, abstract, and country of origin. Of these, 4,217 were excluded for reasons including irrelevance to delayed breast cancer diagnosis, study design, population, setting (e.g., high-income countries), or publication date (outside 2000-2024). The remaining 60 studies met the inclusion criteria and were included in the narrative synthesis. Extracted data were organized and interpreted using the revised Penchansky framework (accessibility, availability, acceptability, affordability, accommodation, awareness). Additional themes included misdiagnosis, competing priorities, and personal factors.

CONCLUSIONS: Multiple modifiable factors contribute to diagnostic delays in LMICs. Addressing them can accelerate diagnosis, improve outcomes, and reduce harm. Targeted improvements in these areas offer significant potential to enhance breast cancer care and save lives in LMICs.

PMID:41608531 | PMC:PMC12835700 | DOI:10.30476/ijcbnm.2025.104511.2632

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Stem cell therapy for degenerative disc disease: A systematic review of preclinical evidence, clinical translation, and future directions

N Am Spine Soc J. 2025 Dec 19;25:100841. doi: 10.1016/j.xnsj.2025.100841. eCollection 2026 Mar.

ABSTRACT

BACKGROUND: Degenerative disc disease (DDD) is a leading contributor to chronic low back pain and global disability. Existing therapies, from conservative management to spinal fusion, do not reverse the underlying molecular degeneration, leaving a critical treatment gap. Given its regenerative capabilities the advent of stem-cell therapy may constitute an ideal solution to fulfill such a therapeutic gap.

METHODS: This PRISMA-compliant systematic review evaluates stem cell-based strategies for intervertebral disc regeneration by examining preclinical evidence, clinical translation, and future directions. Searches of PubMed, Scopus, Web of Science, and related databases (from January 2000-May 2025) identified studies reporting on pain (Visual Analogue Scale), function (Oswestry Disability Index), and structural outcomes (MRI).

RESULTS: Preclinical models uniformly demonstrate meaningful regeneration, including restoration of disc height and extracellular matrix. Clinical evidence, however, is limited: thirteen low to moderate-quality trials show modest, albeit statistically significant, improvements in pain and disability, without compelling imaging proof of biological repair. Short to mid-term safety appears acceptable.

CONCLUSIONS: The use of stem-cell therapy for treatment of degenerative disc disease is constrained by the somewhat hostile and avascular microenvironment of the intervertebral disc. Existing trials exhibit significant methodological weaknesses which substantially impair their application to the daily clinical practice. Future progress will likely depend on incorporating biomaterial-assisted delivery systems, cell-free exosome approaches, biological scaffolds and gene-editing technologies aimed at engineering the disc niche rather than simply focusing on cell replacement.

PMID:41608524 | PMC:PMC12835428 | DOI:10.1016/j.xnsj.2025.100841

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Assessment of the surface characterization, physicochemical and biological properties of mineral trioxide aggregate mixed with different ionic vehicles on diabetic root dentine: a laboratory investigation

BMC Oral Health. 2026 Jan 29. doi: 10.1186/s12903-025-07599-3. Online ahead of print.

ABSTRACT

OBJECTIVE: To comparatively evaluate the effects of mineral trioxide aggregate (MTA) mixed with distilled water (DW), phosphate-buffered saline (PBS), and disodium hydrogen phosphate (DSHP) on the root dentine of teeth affected by diabetes mellitus (DM).

MATERIALS AND METHODS: Five samples of MTA were mixed with either distilled water (DW), phosphate-buffered saline (PBS), or disodium hydrogen phosphate (DSHP). Then, they were assessed for surface characteristics using high-resolution scanning electron microscopy-energy-dispersive X-ray spectroscopy (HRSEM-EDX), surface microhardness via Vickers indentation, and in vitro bioactivity after 21 days of immersion in simulated body fluid. For the other in vitro tests, 82 single-root human permanent premolars (nondiabetic = 41; diabetic = 41) were decoronated to a standardized length of 12 ± 1 mm. Following tubular density evaluation (n = 5) using HRSEM, push-out bond strength (n = 18) and fracture resistance (n = 9) were assessed using a universal testing machine, whereas the cement-dentine interface (n = 9) was analyzed using HRSEM-EDX. The root specimens were then randomly subdivided into subgroups based on the different ionic MTA formulations as follows: subgroup I: MTA + DW, subgroup II: MTA + PBS, and subgroup III: MTA + DSHP. Statistical analysis was conducted using GraphPad Prism 10.4.1, using independent t-tests and two-way analysis of variance with Bonferroni correction for comparisons (P < 0.05).

RESULTS: MTA + PBS exhibited a uniform matrix with distinct crystalline structures and the highest microhardness (69.2 ± 3.97 VHN), followed by MTA + DSHP and MTA + DW test materials. All formulations promoted apatite formation, with MTA + PBS showing dense, homogenous platelet-like crystals. Tubular density was reported to be higher in diabetic dentine (P < 0.05). MTA + PBS demonstrated superior cement-dentine interface, push-out bond strength, and fracture resistance, followed by MTA + DSHP and MTA + DW in both DM and non-DM root dentine specimens (P < 0.05).

CONCLUSION: DM significantly affects the physicochemical and biological properties of root dentine. Among the various test ionic formulations, MTA + PBS exhibited superior surface characteristics, physicochemical, and biological characteristics compared to MTA + DSHP and MTA + DW. Hence, MTA mixed with phosphate ionic vehicles, is clinically recommended for effective endodontic management of diabetic dentine.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:41606578 | DOI:10.1186/s12903-025-07599-3

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Hepatitis B knowledge among nursing students at Jiblah University for medical and health sciences

BMC Public Health. 2026 Jan 28. doi: 10.1186/s12889-026-26391-8. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatitis B virus is a blood borne disease that poses a significant public health problem and is classified as an occupational hazard for healthcare workers, including nursing students. Healthcare workers are four times more likely to contract HBV than the general population. Therefore, a thorough understanding of HBV is crucial for nursing students. This study aimed to assess the level of knowledge about HBV infection among nursing students at Jiblah University of Medical and Health Sciences.

METHODS: A descriptive cross-sectional study was conducted. This study included all 94 students enrolled in the Faculty of Nursing. A standardized, pre-tested questionnaire consisting of three sections was used: students’ sociodemographic data, their knowledge of hepatitis B virus infection, and their knowledge of hepatitis B treatment and prevention. The collected data were analyzed using SPSS version 26. The chi-squared test value was set at 0.05. A p-value less than 0.05 is considered statistically significant.

RESULTS: The results showed that the mean age of the participants was 22.15 ± 2.32 years, and that 57.47% were female. Overall, 73% of students had a good knowledge of hepatitis B virus. Forty-six students (48.9%) in the study group were vaccinated against HBV. A lack of knowledge was found regarding HBV transmission methods. Students’ knowledge of HBV infection was associated with gender and year of study.

CONCLUSIONS: The study indicated that students had a good knowledge of hepatitis B virus infection. There were statistically significant correlations between students’ knowledge of hepatitis B virus infection and their gender and year of study.

PMID:41606557 | DOI:10.1186/s12889-026-26391-8

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The predictive value of combined detection of serum IL-33, TSLP and eosinophils in the treatment effect and exacerbation risk of chronic obstructive pulmonary disease

BMC Pulm Med. 2026 Jan 28. doi: 10.1186/s12890-026-04144-y. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition with high morbidity and mortality. This study aimed to investigate the relationship between interleukin-33 (IL-33), thymic stromal lymphopoietin (TSLP), and eosinophilic granulocyte (EOS) levels and the treatment effect and exacerbation risk of COPD.

METHODS: A total of 225 COPD patients who were diagnosed and treated in our hospital from October 2021 to September 2024 were selected as the research objects for retrospective analysis and study, and were recorded as the COPD group. 200 subjects who underwent physical examination in our hospital at the same period were selected as the control group. The serum levels of IL-33, TSLP and EOS were compared between the two groups. The patients were divided into the effective group (102 cases) and the ineffective group (123 cases) according to the reduction of chronic obstructive pulmonary disease assessment test (CAT) score not less than 2 points or lung function grade not less than 1 grade after 1 week of treatment (considered effective). After a 12-month follow-up, patients were further divided into acute exacerbation (n = 104) and non-acute exacerbation (n = 121) groups according to the occurrence of acute exacerbation (patients’ clinical symptoms deteriorated beyond the daily range in a short period of time and needed to change treatment). The changes of serum IL-33, TSLP and EOS levels in patients with different treatment effects and exacerbation risks were detected. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum IL-33, TSLP and EOS alone and in combination for the treatment effect and malignant risk of COPD. Multivariate Logistic regression was used to analyze the influencing factors of ineffective treatment and exacerbation in COPD patients.

RESULTS: Patients with COPD showed higher serum IL-33 and EOS levels and lower TSLP compared to the control group (P < 0.05). Compared with the effective group, patients in the ineffective group showed significantly higher serum levels of IL-33 and EOS and a significantly lower level of TSLP (P < 0.05). Patients in the acute exacerbation group showed higher serum levels of IL-33 and EOS and a lower level of TSLP than the non-acute exacerbation group (P < 0.05). The area under the curve (AUC) of serum IL-33, TSLP, and EOS in detecting the treatment effect of COPD was 0.803, 0.778, and 0.870, respectively. The AUC of combined detection was 0.938, suggesting that the combined detection had a higher predictive value. The AUC for IL-33, TSLP, and EOS were 0.679, 0.716, and 0.891, respectively, with a combined detection AUC of 0.931. For the assessment of COPD exacerbation risk, the combined detection of three indicators had higher clinical value. Multivariate Logistic regression analysis showed that after adjusting for confounding factors such as age, sex, smoking status, and basic pulmonary function, elevated serum IL-33 and EOS levels were still independent risk factors for treatment failure (P < 0.05), while elevated TSLP level was a protective factor (P < 0.05). In terms of predicting the risk of acute exacerbation, the elevated EOS level was an independent risk factor (P < 0.001), and the independent predictive value of IL-33 and TSLP did not reach statistical significance (P > 0.05).

CONCLUSION: The levels of IL-33 and EOS were significantly increased, and the level of TSLP was significantly decreased in patients with effective treatment and acute exacerbation of COPD. The above indicators could be used as important indicators to predict the treatment effect and malignant risk of COPD, and the combined detection had high sensitivity and specificity.

PMID:41606552 | DOI:10.1186/s12890-026-04144-y

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Investigation of risk factors for autism spectrum disorder in children with tuberous sclerosis complex

BMC Psychiatry. 2026 Jan 28. doi: 10.1186/s12888-026-07804-9. Online ahead of print.

ABSTRACT

OBJECTIVE: Tuberous sclerosis complex (TSC) is a rare disease, and children with TSC are at certain risk for autism spectrum disorder (ASD). This study aims to recognize risk factors for TSC children with ASD by analyzing the clinical characteristics.

METHODS: 171 TSC patients were retrospectively recruited, including 62 patients with ASD, and 109 without. All patients met the diagnostic criteria of TSC recommended in the International TSC Consortium in 2018. The diagnosis of ASD was based on the Diagnostic and Statistical Manual 5th Edition (DSM-5) and the Autism Diagnostic Scale (ADOS).

RESULTS: There was no difference in age at diagnosis, number of unpigmented macules, seizure-free rate, effective rate of drug treatment, concordance of cranial MRI lesion and localization of electroencephalography (EEG) epileptiform discharges between TSC children with ASD and without ASD (p > 0.05). The region of the cranial MRI lesion and cardiac hamartoma might be risk factors of ASD in TSC patients(p = 0.04,p = 0. 013).

CONCLUSIONS: Children with TSC exhibiting frontal lobe lesions or cardiac hamartomas are at a higher risk of developing ASD.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:41606547 | DOI:10.1186/s12888-026-07804-9

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Predictive value of node-RADS scoring system for axillary lymph node metastasis in breast cancer

BMC Med Imaging. 2026 Jan 28. doi: 10.1186/s12880-026-02181-x. Online ahead of print.

ABSTRACT

BACKGROUND: We aimed to evaluate the predictive value of preoperative Node-RADS determination at imaging for axillary lymph node (ALN) involvement in cases of breast cancer.

MATERIALS AND METHODS: Node-RADS was determined in all cases using preoperative breast magnetic resonance imaging (MRI) by two radiologists blinded to pathologic results. The ROC curves and AUCs depicted the overall diagnostic performance of the Node-RADS score for lymph node involvement. In addition, the presence of a flare-like perinodal signal was also evaluated as an imaging feature suggestive of extranodal extension. Size and morphological parameters were assessed separately for their association with metastatic involvement.

RESULTS: Both readers demonstrated high diagnostic accuracy in predicting ALN metastasis using the Node-RADS system, with the best diagnostic performance observed at a cutoff value above Node-RADS 2. In logistic regression analysis, heterogeneous internal texture of the lymph node and flare sign were also found to be statistically significantly associated with invasion (p < 0.05). The presence of a fatty hilum was a statistically significant predictor (p < 0.001) associated with a markedly lower likelihood of lymph node metastasis (OR = 0.019, 95% CI = 0.002-0.153).

CONCLUSION: The Node-RADS scoring system demonstrates high diagnostic reliability and reproducibility in the evaluation of axillary lymph nodes in breast cancer. However, the size criterion for ALN assessment may need to be re-evaluated, and the inclusion of size or extranodal extension parameters in the scoring system should be reconsidered.

PMID:41606527 | DOI:10.1186/s12880-026-02181-x