Nevin Manimala

Infect Dis Ther. 2025 Nov 24. doi: 10.1007/s40121-025-01252-w. Online ahead of print.

ABSTRACT

INTRODUCTION: Patient-reported outcomes (PROs) provide important insights into individuals’ health and well-being. We report PROs from six observational cohort studies in treatment-experienced people with HIV switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in routine clinical practice.

METHODS: Data were pooled from the BICtegravir Single Tablet Regimen (BICSTaR) cohort studies (Asia/Canada/EU/Israel/Japan) and a similarly designed Chinese cohort study (GS-CN-380-5759). Quality of life (QoL; mental/physical health) and HIV treatment satisfaction were self-reported by participants using the generic (non-HIV-specific) 36-item Short Form Health Survey questionnaire and HIV Treatment Satisfaction Questionnaire (HIVTSQ; status [s]/change), respectively. Descriptive statistics and linear mixed models adjusted for potential confounders and interactions, with bootstrapped confidence intervals, were used to analyse PROs through 24 months (12 months for treatment satisfaction).

RESULTS: Of 3724 treatment-experienced participants included, 64.2% were Asian, 89.0% male; median age was 41 years. Baseline Mental Component Summary (MCS) scores were below the population average despite receiving antiretroviral therapy, whereas Physical Component Summary (PCS) scores were above average. At 24 months, observed median MCS score improved from baseline (+ 0.6 [interquartile range [IQR] – 4.3 to + 5.9; p = 0.018]) and median PCS score remained stable (- 0.1 [IQR – 3.3 to + 3.3; p = 0.998]). In all key populations, predicted adjusted MCS/PCS scores showed small improvements or remained stable over time. Treatment satisfaction was high at baseline (median HIVTSQs score 55 [IQR 49-60]), with participants reporting improved treatment satisfaction following the switch to B/F/TAF compared with their previous regimen (+ 27 [19-30] at 12 months). Similar improvements were observed across all key populations.

CONCLUSION: In this large cohort of people with HIV who switched to B/F/TAF in routine clinical practice, mental and physical health scores improved or remained stable over time and treatment satisfaction improved. Further studies are required to elucidate the clinical relevance of PRO tools and how they relate to QoL in people with HIV. Video abstract available for this article.

TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT03580668 (Canada study) and NCT04009057 (Israel study); EudraCT trial identifier, EUPAS22185 (Europe study). Video abstract available for this article. Quality of life and treatment satisfaction in people with HIV switching to bictegravir/emtricitabine/tenofovir alafenamide: Pooled analysis from observational cohort studies – a video abstract.

PMID:41284214 | DOI:10.1007/s40121-025-01252-w

Ther Innov Regul Sci. 2025 Nov 24. doi: 10.1007/s43441-025-00893-w. Online ahead of print.

ABSTRACT

In the context of clinical research, computational models have received increasing attention over the past decades. In this systematic review, we aimed to provide an overview of the role of so-called in silico clinical trials (ISCTs) in medical applications. Exemplary for the broad field of clinical medicine, we focused on in silico (IS) methods applied in drug development, sometimes also referred to as model informed drug development (MIDD). We searched PubMed and ClinicalTrials.gov for published articles and registered clinical trials related to ISCTs. We identified 202 articles and 48 trials, and of these, 76 articles and 19 trials were directly linked to drug development. We extracted information from all 202 articles and 48 clinical trials and conducted a more detailed review of the methods used in the 76 articles that are connected to drug development. Regarding application, most articles and trials focused on cancer and imaging-related research while rare and pediatric diseases were only addressed in 14 articles and 5 trials, respectively. While some models were informed combining mechanistic knowledge with clinical or preclinical (in-vivo or in-vitro) data, the majority of models were fully data-driven, illustrating that clinical data is a crucial part in the process of generating synthetic data in ISCTs. Regarding reproducibility, a more detailed analysis revealed that only 24% (18 out of 76) of the articles provided an open-source implementation of the applied models, and in only 20% of the articles the generated synthetic data were publicly available. Despite the widely raised interest, we also found that it is still uncommon for ISCTs to be part of a registered clinical trial and their application is restricted to specific diseases leaving potential benefits of ISCTs not fully exploited.

PMID:41284211 | DOI:10.1007/s43441-025-00893-w

Discov Oncol. 2025 Nov 24;16(1):2155. doi: 10.1007/s12672-025-04009-6.

ABSTRACT

BACKGROUND: The role of chemotherapy in colorectal cancer (CRC) treatment, particularly in elderly and very young patients, remains controversial. This study aims to evaluate the survival benefits of chemotherapy across different age groups in CRC patients using real-world data.

METHODS: We conducted a prospective cohort study using data from the SEER database from 2010 to 2020. A total of 256,320 CRC patients were included in the final analysis. Chemotherapy status (yes/no) was the primary exposure. Outcomes included overall survival (OS), cause-specific survival, and cumulative incidence of cancer- and non-cancer-specific deaths. Statistical analyses involved multivariable Cox proportional hazards models, and competing risks models, adjusted for key demographic and clinical covariates.

RESULTS: Chemotherapy significantly improved OS in patients aged 45 years and older, with the most substantial benefit in those aged 75-84 years (hazard ratios [HR] = 0.54, 95% confidence interval [CI] = 0.52-0.56) and ≥ 85 years (HR = 0.60, 95% CI = 0.57-0.64). Patients younger than 45 years did not show a significant survival benefit (HR = 1.02, 95% CI = 0.93-1.12). Survival benefit was consistent across tumor locations and most pronounced in stage III (HR = 0.40) and stage IV (HR = 0.39) disease. Competing risks models confirmed reduced cancer-specific mortality in older age groups. Sensitivity analyses excluding early deaths further validated the robustness of these findings.

CONCLUSION: Chemotherapy conferred a survival benefit in patients aged ≥ 45 years, including the very elderly, when selection was based on functional status rather than age alone, whereas no clear benefit emerged in younger patients. This association persisted after multivariable adjustment and across stage-stratified and sensitivity analyses. Given SEER’s lack of regimen, timing, comorbidity, and targeted-therapy detail, cautious interpretation is warranted.

PMID:41284200 | DOI:10.1007/s12672-025-04009-6

Prog Orthod. 2025 Nov 24;26(1):48. doi: 10.1186/s40510-025-00596-w.

ABSTRACT

BACKGROUND: Orthodontic tooth movement (OTM) is a complex biological process triggered by orthodontic forces (OF). This study aims to study the influence of sex and age on the gene expression of the dental pulp (DP) and periodontal ligament (PDL) of human premolars subjected to 7 and 28 days of OF in vivo.

METHODOLOGY: Linear mixed and negative-binomial models were used on previously published RNA sequencing (RNA-seq) datasets of DP and PDL tissue subjected to OF for 7 days and 28 days to verify if the effect of OF depends on sex and age. Differentially expressed genes (DEGs) were identified using false discovery rate and functional analysis was performed.

RESULTS: The datasets consisted of 69 DP and 63 PDL samples from 46 and 41 patients respectively, with similar sex and age distribution. RNA-seq showed that sex did not influence the DP’s gene expression profile, since only one DEG related to immune response was detected after 28-days of OF. In contrast, sex significantly affected PDL: 505 DEGs were found after 7 days of OF, related to bone homeostasis, osteoclastic activity and immune response. Age impacted both tissues; in DP, 18 DEGs related to Ca²⁺ regulation and DNA damage repair were found at 7 days, and 10 DEGs associated with repair and adaptive capacities emerged at 28 days. In PDL, 181 genes related to bone regeneration were identified at 28 days, with no DEGs noted at 7 days.

CONCLUSION: Our study demonstrates that under OF, DP’s reaction is not sex-based, whereas PDL’s is, particularly in the early phase of OTM, with women showing a more pronounced osteoclastic response. Age-related effects in DP tissue primarily influence Ca²⁺ homeostasis and DNA damage repair in early phases, and tissue repair and adaptive responses later. In contrast, age impacts PDL tissue mainly in the later stages of OTM, affecting its regenerative capacity.

PMID:41284150 | DOI:10.1186/s40510-025-00596-w

Clin Rheumatol. 2025 Nov 24. doi: 10.1007/s10067-025-07843-9. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to assess the expression and clinical significance of hsa-miR-661 in peripheral blood mononuclear cells (PBMCs) of patients with primary Sjögren’s syndrome (pSS) and to explore the role of the hsa_circ_0008301/hsa-miR-661/TOLLIP axis in disease progression.

METHODS: A total of 58 pSS patients and 58 age- and sex-matched healthy controls, recruited from the General Hospital of Ningxia Medical University between September 2021 and September 2022, were included. Clinical and laboratory data were collected. Hsa-miR-661 expression in PBMCs was measured using quantitative real-time PCR (qRT-PCR). The interaction between hsa_circ_0008301, hsa-miR-661, and TOLLIP was validated using dual-luciferase reporter assays. Group differences were analyzed using t-tests and χ² tests. Correlations with clinical and laboratory parameters were examined using Spearman correlation and logistic regression. Diagnostic utility was evaluated via receiver operating characteristic (ROC) curve analysis, with P < 0.05 considered statistically significant.

RESULTS: Hsa-miR-661 expression was significantly upregulated in pSS patients compared to controls. Increased levels were associated with longer disease duration, lower C3 and platelet counts, higher ESR, more severe xerostomia, and elevated ESSDAI scores. ROC analysis demonstrated that hsa-miR-661 effectively distinguished pSS patients from healthy individuals and discriminated between high- and low-activity disease states. Functional assays confirmed that hsa_circ_0008301 directly interacts with hsa-miR-661, which targets and regulates TOLLIP.

CONCLUSION: Hsa-miR-661 is markedly elevated in pSS and closely correlates with disease activity and key clinical indicators. These findings suggest its potential as a diagnostic biomarker and therapeutic target in pSS. Key Points • Hsa-miR-661 is markedly upregulated in peripheral blood mononuclear cells of pSS patients and is closely associated with clinical manifestations and disease activity. • It demonstrates strong diagnostic accuracy (AUC = 0.892) and effectively distinguishes between high and low disease activity (AUC = 0.779). • The circRNA_0008301/miR-661/TOLLIP axis provides mechanistic insight into pSS pathogenesis and highlights a potential therapeutic target.

PMID:41284134 | DOI:10.1007/s10067-025-07843-9

Int J Comput Assist Radiol Surg. 2025 Nov 24. doi: 10.1007/s11548-025-03550-7. Online ahead of print.

ABSTRACT

PURPOSE: For diffusion MRI (dMRI) parameter estimation, machine-learning approaches have shown promising results so far including the synthetic Q-space learning (synQSL) based on regressor training with only synthetic data. In this study, we aimed at the development of a new method named synthetic X-Q space learning (synXQSL) to improve robustness and investigated the basic characteristics.

METHODS: For training data, local parameter patterns of 3 × 3 voxels were synthesized by a linear combination of six bases, in which parameters are estimated at the center voxel. We prepared three types of local patterns by choosing the number of bases: flat, linear and quadratic. Then, at each location of 3 × 3 voxels, signal values of the diffusion-weighted image were computed by the signal model equation for diffusional kurtosis imaging and Rician noise simulation. The multi-layer perceptron was used for parameter estimation and was trained for each parameter with various noise levels. The level is controlled by a noise ratio defined as a fraction of the standard deviation in the Rician noise distribution normalized by the average b = 0 signal values. Experiments for visual and quantitative validation were performed with synthetic data, a digital phantom and clinical breast datasets in comparison with the previous methods.

RESULTS: By using synthetic datasets, synXQSL outperformed synQSL in the parameter estimation of noisy data sets. Through the digital phantom experiments, the combination of synXQSL bases yields different results and a quadratic pattern could be the reasonable choice. The clinical data experiments indicate that synXQSL suppresses noises in estimated parameter maps and consequently brings higher contrast.

CONCLUSION: The basic characteristics of synXQSL were investigated by using various types of datasets. The results indicate that synXQSL with the appropriate choice of bases in training data synthesis has the potential to improve dMRI parameters in noisy datasets.

PMID:41284131 | DOI:10.1007/s11548-025-03550-7

Intern Emerg Med. 2025 Nov 24. doi: 10.1007/s11739-025-04211-y. Online ahead of print.

ABSTRACT

BACKGROUND: Acute pain is a common reason for emergency department visits. Opioids remain important for moderate to severe pain but their use is controversial due to safety concerns and variable prescribing practices. Differences in training between emergency medicine specialists and general practitioners may influence opioid administration and prescribing.

OBJECTIVES: To compare opioid administration and prescribing practices between emergency medicine specialists and general practitioners working in Turkish EDs, focusing on comfort, training, guideline adherence, and multimodal analgesia use.

METHODS: This nationwide cross-sectional survey included 200 physicians (100 emergency medicine specialists, 100 general practitioners) from various hospital types. Data were collected through a 17-item online questionnaire distributed via institutional mailing lists and professional societies. Statistical analyses included Chi-square tests, Mann-Whitney U tests, Spearman correlations, and binary logistic regression.

RESULTS: Emergency medicine specialists reported significantly greater comfort with opioid administration and prescribing (29% vs. 21% “very comfortable”; p = 0.0155), more frequent use of clinical guidelines (67% vs. 35%; p < 0.001), and more recent formal training (14% vs. 0% within the past year; p < 0.001). Familiarity with multimodal analgesia was also higher among specialists (96% vs. 89%; p = 0.0372). No significant differences were observed in opioid types used, side-effect concerns, or prescribing frequency. Correlation analysis showed that age and years of experience were positively associated with comfort (ρ = 0.17, p = 0.019; ρ = 0.16, p = 0.020), but not with actual opioid use. In logistic regression, specialty, training recency, and adherence to clinical guidelines independently predicted safe and consistent opioid practice.

CONCLUSION: Opioid administration and prescribing in emergency departments differ substantially between emergency medicine specialists and general practitioners, driven mainly by education and guideline adherence rather than institutional factors. Targeted training and standardized protocols are needed to reduce variability and improve safe, effective pain management in emergency care.

PMID:41284128 | DOI:10.1007/s11739-025-04211-y

Tissue Eng Regen Med. 2025 Nov 24. doi: 10.1007/s13770-025-00765-2. Online ahead of print.

ABSTRACT

BACKGROUND: Mesenchymal stem cells (MSCs) derived from bone marrow (BM), adipose tissue (AD), and umbilical cord (UC) exhibit therapeutic potential in regenerative medicine. However, their properties, including transcriptomic profiles, vary based on tissue origin, passage stage, and isolation method, complicating their clinical standardization. Addressing these unresolved differences requires comprehensive approaches, such as RNA sequencing, to analyze transcriptomic profiles in detail.

METHODS: In this study, RNA-seq was employed to analyze MSC transcriptomes from BM, AD, and UC tissues. UC MSCs were isolated using enzymatic digestion or the Minimal Cube Explant (MCE) method (smumf cells), and transcriptomes of early (P3-4) and late (P10) passages of smumf cells were compared. Differentially expressed genes (DEGs) were identified, followed by transcription factor (TF) and pathway analyses.

RESULTS: Fetal MSCs (UC and smumf cells) exhibited distinct transcriptomic profiles compared to adult MSCs (BM and AD), with 2,208 upregulated and 2,594 downregulated DEGs. Key transcription factors, such as E2F1 and NF-κB1, and pathways, including glycolysis, cholesterol biosynthesis, and TNF-α signaling, were enriched in fetal MSCs. smumf cells demonstrated transcriptomic stability between early and late passages, with only 12 DEGs identified. Additionally, smumf cells showed enhanced innate immune responses and cholesterol metabolism compared to enzymatically isolated UC MSCs.

CONCLUSION: This study provides a comprehensive transcriptomic comparison of MSCs, highlighting the superior transcriptional stability, immunomodulatory capacity, and metabolic flexibility of fetal MSCs, particularly smumf cells. These findings underscore their potential as a reliable cell source for therapeutic applications and encourage further exploration of their clinical application.

PMID:41284123 | DOI:10.1007/s13770-025-00765-2

Lasers Med Sci. 2025 Nov 24;40(1):492. doi: 10.1007/s10103-025-04756-6.

ABSTRACT

Peri-implantitis is one of the most important complications related to dental implants, and there is still no consensus about a protocol for treatment. This study aimed to compare an antimicrobial photodynamic therapy protocol using methylene blue or toluidine blue O, and the efficacy of these two dyes without light activation against human oral biofilm associated with peri-implantitis. Twenty-four dental implants (Classic-CI^®, Systhex Dental Implants) were divided into six groups (n = 4): NC – sterile implants (negative control); PC – contaminated implants (positive control); MB – contaminated implants, decontaminated with methylene blue (0.01%, 1 min); aPDT MB – contaminated implants, decontaminated with antimicrobial photodynamic therapy (MB + red laser); TBO – contaminated implants, decontaminated with toluidine blue O (0.01%, 1 min); aPDT TBO – contaminated implants, decontaminated with antimicrobial photodynamic therapy (TBO + red laser). Microbiologic analysis was performed by counting the colony-forming units (CFUs). Statistical analysis used One-way ANOVA test and Tukey post-test to compare the experimental groups, with a significant level of 5%. Both groups treated with antimicrobial photodynamic therapy were similarly effective against the biofilm, compared to group C (p < 0.001). Dyes alone were similar (p = 0.518) and had no antimicrobial effect. The antimicrobial photodynamic therapy protocol was effective in implant decontamination in vitro regardless of the photosensitizer used, and the dyes without light activation do not seem to be an indicated method for this purpose.

PMID:41284122 | DOI:10.1007/s10103-025-04756-6

Clin Exp Nephrol. 2025 Nov 24. doi: 10.1007/s10157-025-02791-9. Online ahead of print.

ABSTRACT

BACKGROUND: The role of Janus kinase (JAK) 2 in chronic kidney disease (CKD) remains unreported. This Mendelian randomisation (MR) study investigates the causal associations of JAK2 with CKD and provides references for the identification of possible therapeutic targets and the prevention of renal dysfunction.

METHODS: Summary data for JAK2 and various CKD endpoints are extracted from genome-wide association study findings provided by the MRC Integrative Epidemiology Unit and FinnGen. The causal relationships are assessed using inverse variance weighted estimates, weighted median and MR-Egger regression. To ensure rigour, reverse MR, radial MR and leave-one-out approaches are employed for sensitivity analyses, with Cochran’s Q used to assess heterogeneity.

RESULTS: Inverse variance weighted estimates indicate potential two-way causal associations between JAK2 and membranous nephropathy (MN) (odds ratio [OR] = 1.138, 95% confidence interval [CI]: 1.073-1.206; reverse causal association: OR = 1.040, 95% CI: 1.002-1.079). Sensitivity analyses demonstrate that these relationships are relatively robust. An underlying causal relationship between JAK2 and estimated glomerular filtration rate is identified (OR = 0.996, 95%CI 0.993-1.000); however, this becomes non-significant after the radial MR test (P > 0.05). In addition, polycystic kidney disease exhibits a potential causal relationship with JAK2 (OR = 1.066, 95%CI 1.009-1.127).

CONCLUSIONS: Elevated relative expression of JAK2 may represent a potential risk factor for the occurrence of MN. Conversely, patients with MN may exhibit high relative expression of JAK2. These two-way causal associations may inform future efforts aimed at the prevention of CKD and the identification of possible therapeutic targets.

PMID:41284113 | DOI:10.1007/s10157-025-02791-9