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Metabolomic profiling of patients with sepsis-associated encephalopathy

Biomed Khim. 2025 Dec;71(6):441-453. doi: 10.18097/PBMCR1599.

ABSTRACT

Sepsis-associated encephalopathy (SAE) is a condition characterized by acute brain dysfunction developed in the absence of a primary infection in the central nervous system. The aim of this study was to perform a pilot, untargeted metabolomic profiling of the blood plasma of SAE patients to identify metabolic changes potentially associated with the pathological condition and to generate hypotheses for further studies of its pathogenesis, as well as to the search for promising biomarkers, and the assessment of the severity of the patient’s condition. Metabolomic profiling was performed using HPLC-HR-MS, followed by statistical analysis of the obtained data. This blinded, randomized, controlled clinical trial revealed significant differences in the metabolic profiles of the study and control groups. Functional analysis showed the metabolic pathways most affected by pathological processes in SAE patients. These included metabolism of acylcarnitines, lysophosphatidylcholines, and taurine, folate biosynthesis, and the drug metabolism involving the cytochrome P450 pathway. In SAE patients with impaired consciousness, including delirium and coma, decreased levels of long-chain acylcarnitines and lysophosphatidylcholines were observed. The metabolomic profiles of SAE patients differed significantly between the groups of deceased and surviving patients: concentrations of sulfur-containing amino acids were significantly lower in the group of deceased than in the group of survivors. Our study identified 64 candidate biomarkers that could potentially be used to predict sepsis outcomes. However, further study is needed using an expanded and independent cohort of patients.

PMID:41556075 | DOI:10.18097/PBMCR1599

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Token-Level Attribution for Transparent Biomedical AI

Biomed Eng Comput Biol. 2026 Jan 17;17:11795972251407864. doi: 10.1177/11795972251407864. eCollection 2026.

ABSTRACT

BACKGROUND: Explainability (xAI) is critical for fostering trust, ensuring safety, and supporting regulatory compliance in healthcare AI systems. Large Language Models (LLMs), with impressive capabilities, operate as “black boxes” with prohibitive computational demands and regulatory challenges. Small Language Models (SLMs) with open-source architectures present a pragmatic alternative, offering efficiency, potential interpretability, and alignment with data privacy frameworks. This study evaluates whether token-level attribution (TLA) methods can provide technical traceability in SLMs for clinical decision support.

METHODS: The Captum 0.7 attribution library was applied to a Qwen-2.5-1.5B model on 20 breast cancer cases from a publicly available dataset. Hardware requirements were profiled on consumer-grade GPU. Using perturbation-based integrated gradients, we analyzed how clinical input features statistically influenced token generation probabilities.

RESULTS: Attribution heatmaps successfully identified clinically relevant input features, with high-attribution tokens corresponding to expected clinical factors. The model occupied minimal storage, enabling local deployment without cloud infrastructure. This validates that SLMs can provide algorithmic traceability required for regulatory frameworks.

CONCLUSIONS: This proof-of-concept demonstrates the technical feasibility of combining SLMs with perturbation-based xAI methods to achieve auditable clinical AI within practical hardware constraints. While TLA provides statistical associations, bridging toward causal clinical reasoning requires further research.

PMID:41556064 | PMC:PMC12812195 | DOI:10.1177/11795972251407864

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Psychometric assessment of the Chinese version of the perceptions of palliative care instrument in advanced cancer patients: a cross-sectional study

PeerJ. 2026 Jan 15;14:e20622. doi: 10.7717/peerj.20622. eCollection 2026.

ABSTRACT

BACKGROUND: This study aimed to validate the Chinese version of the perceptions of palliative care instrument (C-PPCI) for assessing the perceptions and needs of advanced cancer (AC) patients regarding palliative care in China.

METHODS: The C-PPCI was translated following Brislin’s guidelines and tested for psychometric properties through a cross-sectional survey of 537 AC patients. Internal consistency was evaluated using Cronbach’s alpha, and test-retest reliability was assessed with the intra-class correlation coefficient (ICC). Content validity was examined with the content validity index (CVI), and construct validity was explored using exploratory factor analysis (EFA) and confirmed with confirmatory factor analysis (CFA). Concurrent validity was assessed by correlating the C-PPCI with the Edmonton symptom assessment scale (ESAS) and distress thermometer (DT).

RESULTS: Of 537 recruited participants, 444 completed the questionnaire (response rate: 82.6%). The scale-level content validity index (S-CVI) was 0.99. The C-PPCI demonstrated strong internal consistency, with a Cronbach’s alpha of 0.852 for the total scale (subscale range: 0.820-0.872). Test-retest reliability was good, with an ICC of 0.855 for the total scale (subscale range: 0.751-0.815). EFA yielded a four-domain, nine-factor structure explaining 64% to 75% of the total variance. CFA supported this model with good fit indices (comparative fit index (CFI) = 0.917, Tucker-Lewis index (TLI) = 0.904, root mean square error of approximation (RMSEA) = 0.051, standardized root mean square residual (SRMR) = 0.072). Concurrent validity was supported by significant correlations with the ESAS and DT for most subscales.

CONCLUSIONS: The 35-item C-PPCI is a valid and reliable instrument for measuring Chinese AC patients’ perceptions and needs regarding palliative care, providing a valuable tool for clinicians to enhance palliative care (PC) utilization in this context.

PMID:41556055 | PMC:PMC12812269 | DOI:10.7717/peerj.20622

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Molecular characterization of early-stage multi-primary lung adenocarcinoma by transcriptome sequencing-a retrospective study

PeerJ. 2026 Jan 15;14:e20617. doi: 10.7717/peerj.20617. eCollection 2026.

ABSTRACT

BACKGROUND: To investigate the molecular genetic features of multiple primary lung cancer (MPLC) to provide a basis and new methods for its identification, diagnosis, and treatment.

METHODS: Transcriptome sequencing (RNA-seq) was performed on 16 tissue samples from eight patients with synchronous multiple primary lung adenocarcinoma (sMP-LUAD) and eight tissue samples from eight patients with single primary lung adenocarcinoma (SP-LUAD). Differentially expressed genes selected by bioinformatic methods were validated in 24 sets of sMP-LUAD and SP-LUAD samples using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Based on The Cancer Genome Atlas (TCGA) database, the differentially expressed genes responsible for the biological behavior of lung adenocarcinoma and their clinical significance were analyzed.

RESULTS: Overall, 194 differentially expressed genes were identified (P < 0.05), including 22 up-regulated and 172 down-regulated genes. Two up-regulated (DUOX1 and CACNA2D2) and three down-regulated (GPX8, COL1A2, and COL1A1) genes were selected for validation by qRT-PCR analysis. The qRT-PCR results showed that the expression of DUOX1 mRNA in the sMP-LUAD group was significantly higher (P < 0.05) than that in the SP-LUAD group; mRNA CACNA2D2, GPX8, COL1A2, and COL1A1 expression in the sMP-LUAD group was not statistically different from that in the SP-LUAD group (P > 0.05). Gene ontology (GO) enrichment analysis showed that DUOX1 mRNA was mainly enriched in the entries of positive regulation of wound healing and oxidation-reduction processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that DUOX1 can promote reactive oxygen species (ROS) production and be related to thyroid hormone production. Furthermore, based on the TCGA database, we analyzed the biological behavior and clinical significance of DUOX1 in lung adenocarcinoma using bioinformatics technology. DUOX1 mRNA expression was decreased in all stages and pathological subtypes of lung adenocarcinoma (P < 0.05). Immune infiltration analysis showed that DUOX1 with mast cells and eosinophils was positively correlated (P < 0.05), and Th2 cells were negatively correlated (P < 0.05). Logistic regression analysis showed that the expression of DUOX1 mRNA was significantly correlated with the patient’s age, lymph node metastasis, and pathologic stage (P < 0.05). Kaplan-Meier survival plots showed that low DUOX1 expression was not significantly correlated with OS, DSS, and PFI (P > 0.05). Univariate and multivariate COX regression analysis revealed that DUOX1 mRNA could not be used as an independent factor for predicting prognosis (P > 0.05). Therefore, we developed a predictive nomogram model combining clinicopathological variables and DUOX1 mRNA to predict the survival of patients with lung adenocarcinoma.

PMID:41556052 | PMC:PMC12812280 | DOI:10.7717/peerj.20617

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4-week aerobic exercise training regulates systemic macrophage polarization in obese mice

PeerJ. 2026 Jan 15;14:e20604. doi: 10.7717/peerj.20604. eCollection 2026.

ABSTRACT

BACKGROUND: Obesity is accompanied by chronic low-grade inflammation, largely driven by imbalances in macrophage polarization. While pro-inflammatory M1 macrophages accumulate in adipose tissue and circulation, contributing to insulin resistance and metabolic disruption, alternatively activated M2 macrophages exert anti-inflammatory and tissue-protective effects. Exercise is widely recognized as a non-pharmacological strategy to improve metabolic health; however, the extent to which short-term aerobic training influences systemic macrophage polarization in obesity is not fully understood. This study examined whether a 4-week aerobic exercise intervention alters systemic macrophage polarization in diet-induced obese mice and explored its role in attenuating obesity-related inflammation.

METHODS: Male C57BL/6J mice (8 weeks old) were fed either a standard chow diet (Ch) or a high-fat diet (HF; 60% kcal from fat) for 12 weeks. Following obesity induction, HF-fed mice were assigned to either a sedentary (HF-Sed) or exercise-trained (HF-Exe) group. The training protocol involved treadmill running at moderate intensity, performed twice daily, 5 days per week, for 4 weeks. Plasma concentrations of M1-associated markers (TNF-α, IFN-γ , IL-1β, IL-6) and M2-associated markers (IL-10, Arg1, CD163) were measured by an enzyme-linked immunosorbent assay (ELISA). Statistical differences were analyzed using analysis of variance (ANOVA) with post hoc testing.

RESULTS: After 12 weeks of high-fat feeding, mice exhibited approximately 20% higher body weight than chow controls, confirming obesity induction. Four weeks of exercise training did not significantly reduce body weight but improved metabolic indices, including plasma glucose and insulin sensitivity. HF-Sed mice displayed elevated circulating M1 cytokines, whereas HF-Exe mice had significantly lower levels of IL-6, and TNF-α. Conversely, exercise enhanced M2-associated markers, including IL-10, Arg1, and CD163. Thus, aerobic training shifted systemic macrophage polarization away from a pro-inflammatory toward an anti-inflammatory profile, independent of substantial weight loss.

CONCLUSION: Short-term aerobic exercise is sufficient to promote M2 macrophage polarization and dampen systemic inflammation in obese mice. These findings underline the rapid immunomodulatory potential of exercise and support its role as an effective non-pharmacological approach to counteract obesity-related inflammation and metabolic dysfunction.

PMID:41556049 | PMC:PMC12812270 | DOI:10.7717/peerj.20604

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Influence of posture during mastication on body composition and nutritional intake in individuals with Down syndrome

PeerJ. 2026 Jan 15;14:e20597. doi: 10.7717/peerj.20597. eCollection 2026.

ABSTRACT

INTRODUCTION: Down syndrome is associated with muscular hypotonia and feeding problems. The aim was to assess whether postural alterations during mastication had an impact on body composition, food intake and consumption.

METHODS: Descriptive cross-sectional study with 48 participants (8-45 years). The OMES-E protocol, anthropometric measurements of body composition and 72 h/3 days intake recording were used.

RESULTS: A total of 35.4% of participants reported being overweight or obese. Statistically significant differences were found in body mass index (BMI) (p = 0.022) and body fat percentage (p = 0.005), both being lower in those participants with postural alteration during mastication. Likewise, a significant relationship was observed between saturated fat intake and postural alteration (p = 0.008). Vitamin D intake was lower than the recommended levels in 77.1% of the participants and vitamin E in 95.8%. Phosphorus (P), iron (Fe) and copper (Cu) were consumed in excess by more than 50% of the sample, especially among those with postural alteration during mastication (58.3%, 45.8% and 45.8%, respectively). As for the food groups, significant differences were recorded in beef consumption, with higher intake in the group with postural alteration.

CONCLUSIONS: Individuals with Down syndrome tend to present obesity and/or overweight. Those with a lower BMI and fat percentage presented postural alterations during mastication, associated with a lower overall intake than those without postural alterations. A higher intake of proteins, fats, and B-group vitamins was shown, which points to dietary behaviors that warrant closer attention due to their potential health implications.

PMID:41556046 | PMC:PMC12812275 | DOI:10.7717/peerj.20597

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Prospective multicenter evaluation of glycemic and patient-reported outcomes following transition to a next-generation continuous glucose monitoring system in users of advanced hybrid closed-loop technology

Ther Adv Endocrinol Metab. 2026 Jan 17;17:20420188251407515. doi: 10.1177/20420188251407515. eCollection 2026.

ABSTRACT

AIMS: To assess the real-world impact of transitioning from the Dexcom G6® to G7® system in individuals with type 1 diabetes (T1D) using the Tandem t:slim X2™ with Control-IQ™. Primary outcomes included glycemic control changes, while secondary outcomes evaluated patient-reported outcomes (PROMs) and experiences (PREMs).

METHODS: A 3-month prospective, multicenter, observational study was conducted in individuals previously using Dexcom G6 and Control-IQ. Glycemic control was assessed via TIR70-180 and HbA1c. PREMs and PROMs were measured using validated questionnaires (Diabetes Quality of Life (DQoL), Type 1 Diabetes Life (ViDa1), Diabetes Distress Scale (DDS), and Diabetes Treatment Satisfaction Questionnaire). Statistical analyses were stratified by baseline TIR70-180 (>70% vs <70%) and sex.

RESULTS: The study included 92 participants (mean age 38 ± 13 years), with a baseline TIR70-180 of 76% ± 10%. The overall TIR70-180 remained stable throughout the study. However, among participants with baseline TIR70-180 <70%, a significant increase in TIR70-180 was observed, rising from 61% ± 9% to 65% ± 7% (p = 0.007). In consonance, HbA1c levels showed a significant decline, from 7.3% ± 0.9% to 7.0% ± 0.6% (p = 0.001). In addition, both glucose management indicator (GMI) and mean glucose levels significantly decreased over time, reflecting an overall improvement in glycemic control. These changes (GMI and glucose levels) were consistent across groups, with no significant differences based on baseline TIR70-180 stratification. Quality of life and diabetes distress improved (DQoL, ViDa1, and DDS), especially in participants with lower baseline TIR70-180 and in women. Some reported increased connectivity issues, but none led to treatment discontinuation.

CONCLUSION: In Control-IQ users, the transition to G7® did not significantly impact glycemic control overall. However, a subgroup of patients with suboptimal baseline control (TIR70-180 <70%) may benefit from this change, and enhanced quality of life and diabetes distress, especially in women.

PMID:41556043 | PMC:PMC12812196 | DOI:10.1177/20420188251407515

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Comparative Study of Swab Culture and Tissue Biopsy in Burn Wound Sepsis: A Tertiary Centre Experience

Cureus. 2025 Dec 18;17(12):e99588. doi: 10.7759/cureus.99588. eCollection 2025 Dec.

ABSTRACT

Infection remains a critical cause of mortality among patients with burn injuries, with sepsis and subsequent multiorgan failure being the predominant reasons for death in intensive burn care units. The emergence of nosocomial pathogens in this population makes early identification of infection essential for predicting septicemia and reducing mortality rates. This study aimed to compare the efficacy of surface swab culture versus tissue biopsy culture in identifying pathogenic organisms in burn wounds and examine the correlation between bacterial counts and clinical outcomes.​ A prospective study was conducted enrolling 50 burn patients admitted to the burns ward at Thrissur Medical College, Kerala, India. For each patient, surface swabs and tissue biopsies were collected and processed using conventional culture methods. The statistical analysis was performed using chi-square tests. There was a significant relationship between total body surface area (TBSA) affected and clinical outcome, with a mean TBSA of 45.8%. Notably, 42/50 (84%; p < 0.05) of patients sustained third-degree burns, which was statistically significant in its impact on outcome. Bacterial growth was observed in 48 (96%) of surface swab cultures and 49 (98%) of tissue biopsy samples, with a concordance rate of 19/50 (38%). The most frequently isolated organisms were Pseudomonas aeruginosa 17(34%), Staphylococcus aureus, Klebsiella, and Acinetobacter. A bacterial load greater than 10^5 CFU/ml on quantitative biopsy was significantly associated with poor outcome, as 18/19 (94.7%) patients who died demonstrated counts above this threshold (p < 0.05). In conclusion, both wound surface swab and tissue biopsy cultures were effective in demonstrating pathogen presence, but tissue biopsy was superior in the context of deeper wound invasion. Incorporating tissue biopsy culture into routine management algorithms for high‑risk burn patients may therefore improve prognostication, optimize antibiotic stewardship, and ultimately reduce sepsis‑related deaths in burn units.

PMID:41556028 | PMC:PMC12812218 | DOI:10.7759/cureus.99588

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Insomnia Among Caregivers of Hospitalized Patients in Medical-Surgical Wards: A Cross-Sectional Study

Cureus. 2025 Dec 19;17(12):e99596. doi: 10.7759/cureus.99596. eCollection 2025 Dec.

ABSTRACT

INTRODUCTION: Hospitalization is a stressful event associated with physical, psychological, and financial challenges not only for patients but also for their caregivers. The aim of the present study was to explore the levels of insomnia among family caregivers of hospitalized patients in internal medicine and surgical wards and the associated factors.

METHODS: In the present cross-sectional study, 160 family caregivers of hospitalized patients in internal medicine and surgical wards were enrolled. Insomnia was assessed via the “Athens Insomnia Scale” (AIS). Also, a questionnaire about demographic characteristics and caregivers’ perceptions was completed by the participants. Statistical significance was set at 0.05%. Results: Among the 160 caregivers, 105 (65.6%) were women; 44 (27.4%) were over 60 years old; 124 (77.5%) were admitted to internal medicine wards; 47 (29.4%) had a hospitalization duration of four to six days, while 91 (56.9%) caregivers were the patients’ spouses. With respect to insomnia, the AIS recorded a mean score of 7.4 (±4.6), within a score range of 0-24, while 102 (63.7%) caregivers had an AIS score ≥6. Insomnia was associated with female gender (p=0.001), occupation (p=0.030), hospitalization of patients in surgical wards (p=0.005), staying at hospital (p=0.011), reporting extensive changes in daily routine/lifestyle, extensive illness-related financial concerns, and high uncertainty about the future (p=0.002, p=0.003, and p=0.001, respectively), as well as those who shared the room with more than two patients (p=0.001) and self-reported anxiety due to caregiving (p=0.001).

CONCLUSIONS: Healthcare professionals should be trained to assess insomnia among caregivers of hospitalized patients. Understanding caregivers’ perceptions related to their insomnia helps professionals tailor interventions, improve communication, and provide targeted education. Programs, policies, and support services work best when they are based on caregivers’ real experiences and perceptions.

PMID:41556027 | PMC:PMC12812225 | DOI:10.7759/cureus.99596

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Comparison of Functional Outcomes and Its Association With the Risk Factors in Patients With Anterior and Posterior Circulation Ischemic Stroke

Cureus. 2025 Dec 19;17(12):e99637. doi: 10.7759/cureus.99637. eCollection 2025 Dec.

ABSTRACT

BACKGROUND: Stroke is a highly debilitating condition resulting in significant morbidity and mortality on a global scale. Anterior circulation ischemic stroke (ACIS) and posterior circulation ischemic stroke (PCIS) are distinguished by varying risk factors and functional outcomes. This study is designed to identify the disparities in functional outcomes and their association with risk factors in ACIS and PCIS patients, as assessed by the modified Rankin Scale (mRS) at day 90 post-onset of stroke symptoms.

MATERIALS AND METHODS: This prospective, observational, comparative study was conducted at the Department of Neurology at Bangladesh Medical University (formerly Bangabandhu Sheikh Mujib Medical University [BSMMU]), Dhaka, over 16 months, from May 2023 to September 2024. A total of 116 ischemic stroke patients (58 in the ACIS group and 58 in the PCIS group) were included in this study. A comprehensive medical history and thorough clinical examinations were performed, along with relevant investigations to assess the risk factors. The functional outcomes of the patients were evaluated using mRS by the principal investigator on day 90.

RESULTS: The mean (±SD) age was 59.0 (±12.50) years in the ACIS group and 58.9 (±15.7) years in the PCIS group; this difference was not statistically significant (p = 0.969). ACIS showed a higher prevalence of cardiac illness (p = 0.002), while hypertension (p = 0.026) and smoking (p = 0.007) were notable in PCIS. The study revealed that patients with PCIS exhibited poorer outcomes in comparison to the ACIS group. Among PCIS patients, 32 (55.2%) had poor outcomes (mRS 3-6), whereas among ACIS patients, 15 (25.9%) did; this difference was statistically significant (p < 0.001). Furthermore, ACIS patients were more likely to experience mortality (8.6% vs. 1.7%). Hypertension was associated with a poor functional outcome in both groups (p = 0.023 for ACIS and p = 0.002 for PCIS patients). In contrast, diabetes mellitus and obesity were associated with a worse functional outcome in ACIS and PCIS patients, respectively (p < 0.001 and p = 0.021).

CONCLUSION: Patients with PCIS had a higher prevalence of modifiable risk factors like hypertension and smoking, and showed significantly poorer functional outcomes than those with ACIS at 90 days. Additionally, higher frequencies of cardiac illness and mortality were notable in ACIS. These study findings will help clinicians to plan for specific prevention, acute management, and rehabilitation of Bangladeshi stroke patients.

PMID:41556013 | PMC:PMC12812319 | DOI:10.7759/cureus.99637