2025-12-23 2025, Volume 11 Issue 6

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  • research-article
    Jacek Z. Kubiak
  • research-article
    Lilan Wang, Zixuan Ru, Shengnan Gao, Na Lv, Kerou Li, Hong Qiao

    Background: Serum iodine mainly exists in the form of iodine and iodide ions in thyroid hormones and does not change immediately due to variations in external factors. It is an important indicator reflecting iodine metabolism and actual iodine levels in the body. Given the significant differences in serum iodine among different countries and populations, the standard range of SIC has not yet reached a consensus. To the best of our knowledge, this systematic review and meta-analysis are the first to explore the serum iodine nutritional status of different populations across the country and its correlation with thyroid function. Objective: This meta-analysis aimed to assess reference ranges of serum iodine concentration (SIC) and the potential correlations among SIC, urinary iodine concentration, and thyroid function in various populations globally, providing a reference for the assessment of individual iodine nutritional status. Methods: This study was conducted by searching multiple databases, including PubMed, Web of Science, and China National Knowledge Infrastructure, to gather relevant studies on SIC. Two researchers independently screened the literature and extracted and synthesized the data. The data were then analyzed using Stata software to generate pooled estimates of SIC with 95% confidence intervals (CIs) using forest plots. Results: A total of 48 eligible studies were included, yielding a mean SIC of 88.68 μg/L (95% CI: 84.70-92.65 μg/L). The range of SIC reported across studies was 23.92-183.50 μg/L. Among these, most studies focused on the correlations between SIC and free thyroxine (FT4) (81.0%) and between SIC and FT3 (72.7%). Conclusion: This meta-analysis highlights the importance of SIC as a valuable indicator of individual iodine nutritional status. The findings suggest that SIC is influenced by regional, temporal, and methodological variations, emphasizing the need for standardized testing and reference values. Moreover, the observed associations between SIC and thyroid function markers underscore its clinical relevance in monitoring iodine-related health outcomes. Establishing consistent measurement protocols and population-specific reference ranges will enhance the accuracy of iodine status assessments and support more effective public health interventions. Relevance for Patients: This systematic review provides a preliminary synthesis of currently non-standardized SIC reference ranges. Future large-scale, multicenter studies on SIC testing are needed to establish reference values for assessing individual iodine nutritional status, thereby enabling scientifically informed and precision-based iodine supplementation.

  • research-article
    Ugljesa Malicevic, Jacob Smith, Devendra K. Agrawal, Vikrant Rai

    Background: Diabetic foot ulcers (DFUs) are a severe complication of diabetes mellitus, leading to chronic infections, amputations, and increased mortality despite existing treatments. More effective therapeutics are urgently needed, and animal models provide a critical platform for investigating the molecular mechanisms underlying DFUs. Streptozotocin (STZ)—administered at a low dose to induce type 2 diabetes (T2D) and at a high dose to induce type 1 diabetes—is commonly used in mice and rats in DFU research. Aim: The objective of this study is to highlight the importance of including male and female rats in DFU research. Methods: Both male and female Sprague-Dawley rats, 6-8 weeks old, were fed a high-fat diet for 9 weeks. STZ (25 mg/kg intraperitoneally) was administered weekly from the 6th week to induce T2D. Results: Female rats required a higher dose of STZ compared to male rats. The induction of T2D correlated positively with weight gain, which was greater in males than in females. Conclusion: The findings suggest that in addition to gender and weight, other factors may influence the induction of T2D in rats. Most studies in the literature do not use both sexes in DFU research. The distinct responses to STZ and weight gain observed emphasize the need to include both sexes and employ a more detailed approach in preclinical studies to enhance the understanding of DFU wound healing and translate the findings into potential treatments. Relevance for patients: The multifactorial effect on diabetes development, which differs in males and females, suggests the need to consider etiological, physiological, and demographic factors, such as body weight, gender, age, and body mass index, in the prevention and treatment of diabetes. This will also help in planning the individualized treatment for DFUs.

  • research-article
    Randa Alsadig Almahdi, Sami Ahmed Khalid

    Background: Iron deficiency anemia (IDA) remains a significant global public health concern, particularly among vulnerable populations such as children and menstruating women. Although standard oral iron supplements are effective in replenishing iron stores, their use is often limited by gastrointestinal side effects that negatively impact adherence. Grewia tenax fruits, a traditional Sudanese remedy, are widely used for managing IDA; however, their clinical efficacy has not been rigorously evaluated. Method: This open-label study compared G. tenax chewable tablets with ferrous gluconate in 34 adult females (18-50 years) with confirmed IDA (hemoglobin <12 g/dL). Participants received either G. tenax (five tablets twice daily) or ferrous gluconate (one tablet twice daily) for a period of 4 weeks. Hematological parameters were monitored weekly, and iron profile markers were assessed at baseline and at week 4. Results: Ferrous gluconate produced significantly greater increases in hemoglobin and serum iron levels. Although G. tenax showed more modest hemoglobin improvements, it yielded higher post-treatment ferritin levels (7.82 vs. 7.43 μg/L) and greater reductions in total iron-binding capacity, suggesting enhanced iron storage and regulation. A transient rise in reticulocyte counts observed in the G. tenax group indicates early erythropoietic stimulation. Variability in individual response to G. tenax may be attributed to differences in absorption or metabolism, underscoring the need for personalized approaches. Conclusion: These findings challenge the usual iron dose, highlighting the unique pharmacological effects of G. tenax. Further research is warranted to explore its mechanisms, long-term benefits, and role as a culturally acceptable adjunct or alternative in the management of IDA. Relevance for patients: The study population reflects women who are disproportionately affected by IDA in Sudan, making the findings highly relevant to communities that traditionally rely on G. tenax as a culturally rooted remedy.

  • research-article
    Filipa Madeira, João Miguel Ferreira, Dulce Correia, Nuno Gaibino, Renato Reis, Cicero Roberto Pereira

    Background: In critical care settings, especially during surges such as the COVID-19 pandemic, physicians are often required to make rapid triage decisions under resource constraints. While clinical indicators should ideally guide these decisions, emerging research indicates that non-clinical factors—such as a patient’s race or gender—may inadvertently affect judgment. Aim: This study aims to validate clinical profiles using a decision-making tool and examine the predictive role of clinical and social factors in intensive care unit (ICU) admission decisions under contingency conditions, such as during the COVID-19 pandemic. Methods: A total of 432 ICU admission decisions (trials) were collected from a simulated task in which nine ICU physicians evaluated 48 fictional patient profiles under conditions of limited bed availability. Each participant reviewed all profiles and selected half of the profiles for admission. Each profile included six clinical criteria (e.g., prognosis, comorbidities, and respiratory failure severity) and two non-clinical features (i.e., gender and race). The trial served as the unit of analysis. Multilevel logistic regressions assessed the predictive power of clinical and social variables on acceptance decisions, omission errors (rejecting qualified candidates), and false alarms (accepting less qualified candidates). Results: The findings demonstrate that participants relied primarily on clinical information: high-scoring profiles were admitted more often (67.4% and 52.5%) than lower-scoring ones (37.5% and 13.5%) (p<0.001). However, social factors also shaped decisions. Male candidates were more likely to be admitted than females (b = −0.51; t = −4.35; p<0.001; 95% confidence interval [CI] = [−0.75, −0.27]), and Black candidates were admitted more than White candidates (b = −0.52; t = −3.34; p<0.001; 95% CI = [−0.85-−0.19]), even when less qualified, thereby suggesting possible overcorrection. Conclusion: Although clinical criteria primarily guided ICU admission decisions, social characteristics also subtly influenced outcomes. Together, these findings validate the novel decision-making paradigm as a valuable tool for assessing both clinical accuracy and the presence of social bias in triage contexts. They also provide empirical evidence that, under pressure and uncertainty, healthcare professionals may be susceptible to the influence of social cues. Relevance for patient: This study explores how critical care physicians decide who receives life-saving treatment in ICUs, especially during times of crisis when medical resources are limited. By simulating real-world triage situations, the research shows that even experienced clinicians may be influenced by non-clinical factors—such as a patient’s race or gender—despite their intention to prioritize clinical indicators. These findings highlight the need for increased awareness and targeted training to reduce unconscious bias in clinical decision-making.

  • research-article
    Maria Santina Ler, Miriam Veneziano, Alfonsina D’Iorio, Gennaro Cordasco, Gabriella Santangelo, Anna Esposito

    Background: Dementia causes significant disability worldwide and has no cure. The only way to improve the quality of life of those affected is through early intervention. For this reason, the development of effective diagnostic tools is a priority for healthcare systems and researchers. Handwriting and drawing, which engage multiple cognitive and motor areas, have shown promise in detecting early signs of dementia. However, findings in this field remain inconsistent, largely due to a lack of standardized protocols. Aim: This study aims to investigate the discriminatory power of graphomotor analysis in distinguishing individuals with Alzheimer’s disease (AD) from healthy controls (HC) by examining the contribution of dynamic handwriting features and task-related characteristics within an easy-to-use and multi-task protocol. Methods: Patients with AD (n = 14) and HC (n = 25) were asked to complete five drawing and two writing tasks, and their online data were recorded using a digital tablet. Results: Significant differences (p<0.05) between groups were observed for time- and ductus-related features in almost all tasks, while pressure, space, and inclination features did not differ significantly. Conclusion: Although certain graphomotor characteristics are more sensitive than others, analyzing them together yields a detailed functional profile of patients. Overall, the study provides evidence of the effectiveness of handwriting analysis in identifying several symptoms associated with dementia. The protocol warrants further validation with a larger sample. Relevance for patients: The proposed protocol highlights the potential of a handwriting-based tool as an ecologically valid, objective, and accessible method for assessing and monitoring dementia. Adopting up-to-date digital approaches responds to the need for more sensitive tools that align with technological and cultural changes within the population. This could consequently simplify screening, improve access to treatment, and enhance the quality of life for patients and their caregivers.

  • research-article
    Xiaoying He, Tang Xiao, Haifang Zhao, Xinyue Huang, Sheng Xu, Junfeng Liu, Yunxiang Wang, Jie Yin, Yong Zhou, Rui Qi, Ruijuan Heng, Pan Qi

    Background: Increasing evidence underscores the association between chronic inflammation and carcinogenesis. Aim: The aim of the study is to investigate the association between the neutrophil percentage-to-albumin ratio (NPAR) and breast cancer (BC) risk. Methods: This analysis utilized cross-sectional data from 16,993 participants enrolled in the National Health and Nutrition Examination Survey from 1999 to 2016. To investigate the link between NPAR and BC risk, weighted multivariate logistic regression models were applied. Nonlinear associations were explored using restricted cubic spline (RCS) models. Furthermore, a nomogram incorporating NPAR was constructed for risk stratification, and its predictive accuracy was evaluated using receiver operating characteristic curve (ROC) analysis. Results: After adjusting for potential confounders, elevated NPAR levels showed a significant positive association with BC (odds ratio [OR] = 1.12, 95% confidence interval [95% CI]: 1.08-1.16; p<0.001). Compared with the reference quartile (Q1), progressively increasing ORs associated with BC were observed across ascending NPAR quartiles: Q1: OR 1.05 (95% CI: 0.78-1.42), Q2: OR 1.35 (95% CI: 1.02-1.79), and Q3: OR 1.47 (95% CI: 1.12-1.93). Analysis using RCS indicated a linear relationship where increasing NPAR levels were associated with a higher risk of BC. The predictive model incorporating NPAR demonstrated strong accuracy for BC prediction, achieving an area under the ROC curve of 0.8068 (95% CI: 0.7904-0.8232). Conclusion:Our findings reveal a significant dose-dependent association between NPAR and BC risk in a nationally representative sample from the United States. Although cross-sectional designs preclude causal inference, longitudinal studies should validate these observations and explore underlying biological mechanisms. Relevance for patients: NPAR could potentially serve as a novel biomarker to predict BC risk in patients.

  • research-article
    Jenny-Hoa Q. Nguyen, Fudan Zheng, Yuan Xiong, Mahesh N. Samtani

    Background: In pharmacometric analyses, binary dose-response outcome data are used to understand drug potency through the pharmacologic parameter, Effective dose 50 (ED50). Optimal treatment strategies can be developed by characterizing a drug’s dose-response curve, which provides insights into the theoretical maximum effect and the steepness of the curve in response to changes in dose or exposure. Approaches for analyzing group-level response data have not been systematically described in pharmacometric literature, although they are commonly applied in the statistical literature. Aim: This study demonstrates the use of R to analyze grouped or ungrouped binary data, with a focus on pharmacometric applications. Methods: Simulated data were generated to represent a hypothetical Phase 2, dose-ranging, placebo-controlled, randomized clinical trial of drug X, consisting of 250 participants randomized into five distinct cohorts, including a single placebo arm. Linear and non-linear Emax models were fit to the simulated data. Results: Both grouped and ungrouped data approaches produced identical final parameter estimates in logistic regression using the linear and Emax models. The same ED50 value for drug X was obtained from both approaches in the Emax model. Conclusion: This study demonstrates the various methods by which summary- or subject-level binary data can be analyzed using R to model binary response data. Relevance for patients: This work helps bridge the gap between statistical and pharmacometric analysis techniques in the context of binary data analysis. This type of data may facilitate comparative assessments of drug potency and maximal effect using publicly available information from scientific publications or regulatory approval documents.