Nevin Manimala

Methods Mol Biol. 2025;2920:141-160. doi: 10.1007/978-1-0716-4498-0_9.

ABSTRACT

Myalgic encephalomyelitis/chronic fatigue syndrome is a post-viral/stressor syndrome that has a complex pathophysiology reflecting multiple changes in many cell transcripts and proteins. These changes imply a change in the regulation of gene expression at the level of the DNA. A significant contributor to this is the modulation of the methylation at specific sites within regulatory regions throughout the genome that can either enhance or dampen expression depending on whether methylation is reduced or increased, respectively. DNA methylation can be analyzed by array technology or by reduced representation bisulfite sequencing (RRBS) or whole genome bisulfite sequencing (WGBS). This chapter describes RRBS, which has been very effective at analyzing the methylation states of ME/CFS patients both in single time point studies and in longitudinal studies with individual patients, for example, following a relapse recovery cycle. Here, we describe the step-by-step experimental methodology of how RRBS has been applied to DNA samples from ME/CFS patients and the analytical platforms used to detect the methylation changes that are statistically significant between patients and health controls. It has the potential to provide molecular biomarkers for a diagnostic test or to follow the progression of the condition in patients or through relapse/recovery fluctuations that occur frequently through the ongoing course of the disease. When effective therapies become available it has the potential to monitor the effectiveness on individual patients under treatment.

PMID:40372682 | DOI:10.1007/978-1-0716-4498-0_9

Qual Life Res. 2025 May 15. doi: 10.1007/s11136-025-03988-x. Online ahead of print.

ABSTRACT

PURPOSE: This 3-study paper aimed to develop and validate a self-reported Health-Related Quality of Life Pictorial Inventory for Early Childhood Children (HEALTH-PIC). The scale was designed to overcome existing barriers of parent-proxy response styles such as observation bias and offer an alternative to age-suited literary questionnaires to assess self-reported health-related quality of life, including physical health, emotional health, social health and school health in early childhood.

METHODS: Each study targeted a specific aspect of scale development, employing distinct samples to refine and validate the inventory. Study 1 involved item development/revision, which utilized a panel of 10 experts (Mean_age = 34.8, SD = 4.9) and 25 parents (Mean_age = 38.9; SD = 4.1) via the Delphi method to revise the scale and establish agreement. Study 2 is a cross-sectional study that invited a sample of 22 primary school students (Mean_age = 6.18, SD = 0.39) and 20 kindergarten students (Mean_age = 4.55, SD = 0.50) to establish face validity amongst primary respondents. Finally, Study 3 is a cross-sectional study that invited 342 parent and child (Mean_age = 6.30, SD = 1.31) dyads to complete the HEALTH-PIC and reference health-related quality of life (HRQoL) questionnaires to establish the questionnaire’s factorial, concurrent, discriminant and criterion validity in addition to internal consistency.

RESULTS: Scale items in Study 1 were developed alongside experts and parents with a strong theoretical and statistical support calculated using Aiken’s agreement (Aiken’s V p < 0.05), ensuring that the items were clear, accurate and applicable for children. In Study 2, we ensured that primary respondents of different ages were able to accurately identify the pictorial images (Aiken’s V p < 0.05) and complete the questionnaire when the scripted instructions were read aloud. In Study 3, structural equation modelling of the HEALTH-PIC demonstrated a robust factor structure (CFI and TLI > 0.99; RMSEA and SRMR ≤ 0.08), concurrent validity, discriminant validity, criterion validity and an acceptable level of internal consistency (i.e., Cronbach’s α = 0.60-0.66).

CONCLUSION: The findings of the three studies provide preliminary evidence to support the content validity and construct validity of the HEALTH-PIC. This novel pictorial scale not only provides a reliable and valid assessment of the multidimensional aspects of health-related quality of life among children but can also overcome existing barriers of parent-proxy or age-suited questionnaires.

PMID:40372663 | DOI:10.1007/s11136-025-03988-x

J Urban Health. 2025 May 15. doi: 10.1007/s11524-025-00979-8. Online ahead of print.

ABSTRACT

Crowded living conditions are associated with negative health outcomes, particularly for children. Federal rental assistance may reduce household crowding by improving access to affordable housing for low-income families. We leveraged NHANES data linked with HUD administrative rental assistance records to examine relationships between different forms of HUD rental assistance and multiple measures of crowding for households with children. We found a statistically significant reduction in the odds of crowding for those currently receiving HUD assistance compared to a control group who entered rental assistance within 2 years of their NHANES interview (95% CI, 0.39 to 0.93). The specific relationships between rental assistance and crowding and the magnitude of these associations varied by rental assistance type (public housing, multi-family, and vouchers). Fewer than 1 in 4 eligible households receive rental assistance. Our findings suggest that expanding access to this resource can reduce household crowding and its adverse impacts on health and well-being.

PMID:40372662 | DOI:10.1007/s11524-025-00979-8

Cardiovasc Drugs Ther. 2025 May 15. doi: 10.1007/s10557-025-07714-0. Online ahead of print.

ABSTRACT

PURPOSE: SGLT2i role in the treatment of heart failure (HF) regardless of clinical presentation and left ventricular ejection fraction (LVEF) has been widely proven and real-world data regarding patients with HF and ischemic heart disease (IHD) and, in particular with recent acute coronary syndrome (ACS) and de novo HF, are lacking. We aim to evaluate the occurrence of the composite of cardiovascular death (CV)/ HF hospitalization (HFH), all-cause death, CV death and HFH at 6 months follow up, in patients with HF due to IHD as well as in recent ACS who introduced SGLT2i during the index hospitalization.

METHODS: The present is an observational, prospective, single center study, enrolling patients with a diagnosis of HF due to IHD as primary etiology. According to SGLT2i introduction timing, two groups were created: pre-discharge (G1) or post-discharge (G2) introduction. A sub-analysis in patients admitted due to ACS has been performed.

RESULTS: A total of 222 consecutive patients have been enrolled from April 2022 to April 2024 and were followed-up for a period of 6 months. At multivariate Cox regression analysis, statistically significant differences have been observed between the two groups in terms of the composite CV death/HFH (HR = 0.24; 95%CI [0.101-0.564]; p = 0.001), all-cause death (HR = 0.27; 95% CI [0.100-0.725]; p = 0.009), CV death (HR = 0.32; 95%CI [0.101-0.999] p = 0.045) and HFH (HR = 0.31; 95%CI [0.098-0.963]; p = 0.043). Patients with ACS treated with SGLT2i before discharge showed a reduced rate of CV death/HFH (log-rank p = 0.008), CV death (log-rank p = 0.015) and all-cause death (log-rank p = 0.005) compared to patients who were not treated with SGLT2i before discharge. In this subpopulation, no differences have been observed in terms of HFH (log-rank p = 0.155). Significant differences in term of CV death/HFH (log-rank p = 0.039) have been observed in de novo HF patients, but not in terms of the other study endpoints.

CONCLUSIONS: The early in-hospital introduction of SGLT2i reduced the occurrence of the composite CV death/HFH, all-cause death, CV death and HFH in patients with ischemic cardiomyopathy. In the subgroup analysis of patients admitted due to ACS, the introduction of SGLT2i during the index hospitalization resulted in a significant reduction of the composite CV death/HFH, CV death and all-cause death, but not in HFH. The same therapeutic strategy resulted in reduced rate of CV death/HFH in the de novo HF subpopulation.

PMID:40372630 | DOI:10.1007/s10557-025-07714-0

Arch Orthop Trauma Surg. 2025 May 15;145(1):296. doi: 10.1007/s00402-025-05915-8.

ABSTRACT

INTRODUCTION: In humeral shaft fractures, the presence of a free bone fragment, called the third fragment or butterfly fragment, is thought to induce non-union. We hypothesised that non-union and subsequent reoperations could be reduced by performing cerclage wiring for fragments, in addition to intramedullary nailing for fractures with the third fragment. This study aimed to examine the effectiveness of cerclage wiring for the third fragments associated with humeral shaft fractures.

MATERIALS AND METHODS: This study included patients with humeral shaft fractures involving the third fragment, who underwent osteosynthesis with intramedullary nailing at our institution between April 2013 and June 2024. The patients were divided into two groups: those who underwent osteosynthesis using an intramedullary nail alone (Group1) and those who underwent osteosynthesis using an intramedullary nail with cerclage wiring (Group2). Patient and injury characteristics, surgical time, intraoperative blood loss, postoperative complications, fracture healing, time to bone union, and reoperation were investigated and compared between the two groups.

RESULTS: Sixteen patients were included in Group1 and 27 patients were included in Group2. There were no significant differences in patient characteristics or injuries. Surgical time was significantly longer (p = 0.01) and intraoperative blood loss was significantly greater (p = 0.01) in Group2. There were no significant differences in the rates of infection and postoperative nerve paralysis (p = 1, 0.522). The rates in non-union was significantly higher in Group1 (p = 0.05). There were no significant differences in reoperation rate (p = 0.137). In cases where fracture healing was achieved, the time to bone union was significantly longer in Group1 (p < 0.001).

CONCLUSION: Cerclage wiring, in addition to intramedullary nailing for fractures with a third fragment, may prevent non-union. Although the addition of cerclage wiring significantly increased the surgical time and intraoperative blood loss, there was no increase in postoperative complications.

PMID:40372626 | DOI:10.1007/s00402-025-05915-8

Neuropsychol Rev. 2025 May 15. doi: 10.1007/s11065-025-09661-x. Online ahead of print.

ABSTRACT

The purpose of this systematic review was to synthesize the current evidence on motor learning in mild cognitive impairment (MCI). A search of five databases returned a total of 6058 references, 10 of which met criteria for inclusion in this review. The existing evidence was notably variable with an overall moderate risk of bias. Eight articles compared behavioral motor learning outcomes in MCI and age matched, non-cognitively impaired (NCI) samples. In 37.5% of these studies, the degree of motor skill acquisition in the MCI group was statistically significantly less than in the NCI group. Skill retention was only compared between MCI and NCI samples in one article, which reported a relative reduction in MCI group performance following a 24-h, no-practice delay. Importantly, none of the included articles examined motor skill transfer. We discuss possible sources of heterogeneity among collective findings including variability in motor tasks, outcome measurement, and research design. Further research is needed to support a comprehensive understanding of motor learning in the early stages of age-related cognitive decline. Future investigations should emphasize functional motor tasks and clinically relevant learning outcomes, including retention and transfer of motor skills, while controlling for potentially confounding factors such as motivation and sleep performance. This systematic review was registered with PROSPERO international prospective register of systematic reviews (registration ID CRD42023417329).

PMID:40372622 | DOI:10.1007/s11065-025-09661-x

Drugs Real World Outcomes. 2025 May 15. doi: 10.1007/s40801-025-00494-x. Online ahead of print.

ABSTRACT

BACKGROUND: In early 2022, new treatment recommendations for heart failure (HF) were introduced in Sweden.

OBJECTIVE: This study aims to evaluate and analyze the pharmaceutical treatment patterns of HF patients over time in Sweden, in relation to the updated treatment recommendations.

METHODS: This observational study is based on registry data. The study population consisted of patients ≥18 years old who, at any time between 2017 and 2023, had an HF diagnosis, defined using ICD-10 code I50 (n = 212,757). Descriptive statistics were presented for the study population. Based on data from the national drug prescription registry, the treatment patterns between 2021 and 2023 were analyzed using biannual datasets before and after the introduction of treatment recommendations.

RESULTS: The mean age of the study population was 79 years and 56% were men. The utilization of quadruple therapy and SGLT2 inhibitors, both as monotherapy and in combination, increased over time, with a rising trend already apparent prior to the introduction of the updated treatment recommendations. At the end of 2023, about 30% of the incident HF population had at least tried quadruple therapy. Furthermore, a growing number of diverse treatment pathways among HF patients was observed over time, which may indicate an increased consideration for individualized treatment.

CONCLUSIONS: Even though the implementation of the treatment recommendations for HF is not yet optimal, this study found a notable adoption of quadruple therapy in Sweden. There was an increased use of SGLT2 inhibitors and quadruple therapy, beginning even before the introduction of the updated Swedish treatment recommendations.

PMID:40372621 | DOI:10.1007/s40801-025-00494-x

J Cancer Educ. 2025 May 15. doi: 10.1007/s13187-025-02648-5. Online ahead of print.

ABSTRACT

Symptom management is one of the major concerns of cancer survivors, including Asian American breast cancer survivors (ABS) during their survivorship process. The purpose of this randomized intervention study was to determine the efficacy of a technology-based educational intervention in decreasing multiple domains of symptom experience among ABS. This was a part of a randomized clinical trial with repeated measures among 199 ABS recruited through online and offline groups/communities for Asian Americans. The intervention was a technology-based educational (information and coaching/support) program using computers and mobile devices to change health behaviors to improve the women’s survivorship experience. The data were collected using multiple items on background and disease factors, and the Memorial Symptom Assessment Scale-Short Form (MSAS-SF). The data analysis was conducted using an intent-to-treat approach. Although the differences were not statistically significant, all multiple domain symptom scores of the intervention group decreased from pre-test to post 3 months, while only psychological symptom distress scores of the control group decreased from pre-test to post 3 months. Depending on the domain of symptoms, the significant mediators, with total, direct, or indirect effects, were different at different time points. For instance, attitudes, perceived barriers, social influences, social support, and self-efficacy showed significant total mediation effects on the total symptom distress scores only at pre-test (p < 0.05). The efficacy of a technology-based education intervention was supported in decreasing symptoms among ABS. Health educators need to consider that culturally tailored technology-based educational interventions could help improve the symptom experience of ABS.

PMID:40372611 | DOI:10.1007/s13187-025-02648-5

Photochem Photobiol Sci. 2025 May 15. doi: 10.1007/s43630-025-00733-8. Online ahead of print.

ABSTRACT

Understanding the relationship between molecular structure and bioactivity is crucial for optimizing porphyrin-based therapeutics. By integrating cheminformatics techniques with machine learning models, our work enables the efficient classification of compounds based on their molecular structures and their growth inhibition capabilities (IC₅₀). A dataset of 317 porphyrin derivatives was compiled, incorporating molecular descriptors and biological activity data. Descriptive statistical analysis was performed to examine compound distribution and key features. Clustering analysis was conducted using hierarchical clustering and fingerprint similarity matrices to classify compounds based on structural similarity. Lipinski’s Rule of Five was applied to assess drug-likeness, while Murcko scaffold analysis identified core structural patterns. Tumor response data were analyzed to evaluate therapeutic efficacy. Machine learning models were implemented to predict bioactivity. Descriptive statistics highlighted bioactive compounds, with TMPyP4 and Temaporfin being the most studied. Quantitative estimation of drug-likeness and the number of aliphatic carboxylic acids were identified as the most influential descriptors among others for bioactivity. Hierarchical clustering segmented porphyrins into nine structural groups. The analysis identified 168 pIC₅₀ active compounds, with 31 meeting Lipinski’s criteria, and 11 overlapping as both effective and bioavailable. Tumor response analysis revealed three porphyrins achieving 100% response. Logistic Regression emerged as the best-performing model, achieving 83% accuracy, demonstrating robust predictive capabilities. This study successfully characterized porphyrin derivatives, reviewing key molecular features influencing bioactivity and evaluating their therapeutic potential. It highlights the potential of machine learning in predicting the biological activity status of porphyrin derivatives.

PMID:40372610 | DOI:10.1007/s43630-025-00733-8

Eur J Clin Invest. 2025 May 15:e70068. doi: 10.1111/eci.70068. Online ahead of print.

ABSTRACT

BACKGROUND: Torque teno virus (TTV) is not known to cause disease in humans; however, chronic inflammatory conditions and immunosuppression states can favour TTV replication. This study aimed to verify the effectiveness of TTV as an immune biomarker.

METHODS: The protocol of this review was registered in PROSPERO (CRD42022331049) and performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

RESULTS: Thirty-three articles were selected and different groups of patients were assessed. In the solid organ and hematopoietic stem cell transplant groups, most studies reported that TTV viral load (VL) was highly detectable after transplantation and compared to controls, but the association with immune parameters showed conflicting results. In melanoma patients, no statistical difference in TTV VL was identified between susceptible and treatment-resistant patients. In lung cancer patients, viral load increases significantly with disease progression but decreases after chemotherapy. HIV-positive patients showed a higher VL than controls, but an inverse correlation with CD4+ was observed in half of the studies. Although 57.14% of all studies presented a low risk of bias, significant differences were observed between studies, particularly in the choice of the analyzed outcome, the parameter used to evaluate the patient’s immune status, the presence of a control group, and the sample collection time points.

CONCLUSIONS: Although TTV seems to have the potential to be a promising biomarker of immunosuppression, further high-quality prospective clinical studies are still needed.

PMID:40371633 | DOI:10.1111/eci.70068