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PubMed2026

Surgical management of esophageal atresia with tracheoesophageal fistula in extremely low birth weight neonates: A systematic review.

BACKGROUND: Surgical management of esophageal atresia/tracheoesophageal fistula (EA/TEF) in extremely low birth weight (ELBW) neonates remains challenging and controversial. This study systematically reviews surgical strategies and outcomes in this population. METHODS: Following PRISMA guidelines, Cochrane, Embase, MEDLINE, Scopus, and Web of Science (2004-2024) were searched in February 2025 for studies on surgical management of ELBW neonates with EA/TEF (PROSPERO CRD42025636228). Fatal chromosomal abnormalities were excluded. Demographics, comorbidities, surgical techniques, and complications were analyzed descriptively. Risk of bias was assessed. RESULTS: Eleven publications (five case reports and six case series) comprising 30 patients (Gross type B/C = 1/29) met the eligibility criteria. Mean gestational age was 28.1 (23-34) weeks, and mean birth weight was 760.4 (422-995) g. Twelve primary repairs (PR) and 18 delayed primary repairs (DPR) were performed, including staged repair (n = 11), lower esophageal banding (n = 4), and other techniques (n = 3). Postoperatively, four anastomotic leaks were managed conservatively, six strictures and one recurrent TEF required endoscopic intervention, three fundoplications and two aortopexies were reported (follow-up: 1-198 months, n = 19). Overall mortality was 30% (PR: 8.3%; DPR: 44.4%). Mortality was 60% among neonates with major congenital heart defects (CHD) and 40% among those with VACTERL association. EA/TEF-related complications contributed to 33.3% of deaths. CONCLUSIONS: Mortality in this cohort remains high, particularly with major CHD, and is largely unrelated to EA/TEF-specific complications. In selected cases, PR appears feasible as an alternative to DPR, although conclusions are limited by the small sample size and heterogeneous studies.

Humans↗
PubMed2026

Cefoxitin versus cefotaxime as empirical treatment of spontaneous bacterial peritonitis in liver cirrhotic patients: randomized controlled clinical trial.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a severe complication of cirrhosis requiring immediate empirical antibiotic therapy. Third-generation cephalosporins are the traditional agents of choice; however, increasing clinical failure rates necessitate the evaluation of alternative antibiotics to ensure optimal therapeutic outcomes. The aim was to investigate the efficacy of cefoxitin versus cefotaxime for SBP treatment. METHODS: A randomized clinical trial was conducted on 140 cirrhotic patients with community-acquired SBP at Al-Rajhy Liver University Hospital, Assiut, Egypt. Patients were randomized to receive either cefotaxime (n = 70) or cefoxitin (n = 70), 2 g every 8 h for 5 days. Polymorphonuclear neutrophil (PMN) counts were measured upon admission, on Day 2 and on Day 5. Clinical response rates at Days 2 and 5, development of hepatorenal syndrome, length of stay and mortality were assessed. RESULTS: According to intention-to-treat analysis, clinical response rates at Day 2 were 74.2% in the cefotaxime group and 80% in the cefoxitin group, while at Day 5, they were 71.4% and 74.3%, respectively (P = 0.704). The PMN counts at Days 0, 2 and 5 showed no significant differences between the cefotaxime and cefoxitin groups (P = 0.889, 0.909 and 0.360, respectively). The incidence of hepatorenal syndrome was 7.1% in the cefotaxime group compared with 8.6% in the cefoxitin group (P = 0.753), and mortality was 15.7% and 12.9%, respectively (P = 0.629). CONCLUSIONS: Cefoxitin showed comparable effectiveness to cefotaxime but may be utilized in selected clinically stable SBP patients.

Humans↗
PubMed2026

Effectiveness of Platelet Rich Plasma in Reducing Oronasal Fistula and Scar Width in Primary Cleft Lip and Palate Repair-A Systematic Review and Meta-Analysis.

This review aimed to investigate platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) efficiency in reducing oronasal fistula during primary cleft lip and palate repair. An extensive search of PubMed, Google Scholar, Global Index Medics (WHO), PubMed Scopus, Cochrane Central, Proquest was performed up to march 2025. Eligible studies included prospective RCTs and non-randomized controlled trials in human subjects. Patients aged 6-24 months undergoing primary cleft lip and palate repair were involved. Interventions involved intraoperative use of PRP/PRF compared with controls without PRP/PRF. The primary outcome was occurrence of oronasal fistula; secondary outcomes were scar width, wound infection and postoperative bleeding with wound dehiscence. Study selection followed PRISMA guidelines, and the risk of bias was determined with the ROB-2 and ROBINS-I method of assessment. Seven studies met the required criterion and were qualitatively synthesized. Evidence suggested that PRP/PRF application was associated with a lower incidence of oronasal fistula and reduced scar width compared with controls. Additional benefits included accelerated wound healing and faster recovery. The use of autologous PRP was also reported to decrease the need for further surgical interventions. However, the certainty of evidence was limited due to small sample sizes and methodological heterogeneity. PRP and PRF show promising benefits in cleft lip and palate repair, particularly decreased fistula formation and reduced scar width. Nevertheless, current evidence is of low to very low certainty. Larger, well-designed randomized trials are required to validate the results obtained. Trial Registration: PROSPERO registration no. CRD420251032421.

Humans↗
PubMed2026

Auditory brainstem response in the identification of cochlear synaptopathy in aged rodents: a systematic review with meta-analysis.

PURPOSE: This systematic review and meta-analysis evaluated the diagnostic performance of auditory brainstem response (ABR) for identifying age-related cochlear synaptopathies in rodents. METHOD: Following PRISMA guidelines, searches were conducted in PubMed/MEDLINE, Cochrane Library, Scopus, Embase, Web of Science, SciELO, LILACS, and gray literature. Studies evaluating CS in naturally aged rodents using short-latency auditory evoked potentials (AEPs) were included. Study selection, data extraction, risk-of-bias (JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies), and certainty of the evidence (GRADE® system) assessment were conducted independently by two reviewers. Meta-analyses were performed using a random-effects model, with standardized mean differences and 95% confidence intervals. ABR wave I amplitudes were analyzed for click (80 and 90 dB SPL) and tone-burst stimuli stratified by frequency. RESULTS: Among 3,008 identified records, 12 studies were included in the review and five in the meta-analysis. All included studies used ABR measures to investigate CS, with wave I amplitude being the most frequently evaluated biomarker. Meta-analysis demonstrated a significant reduction in ABR wave I amplitude in aged rodents compared with young controls for both click- and tone-burst-evoked responses. Tone-burst ABR showed no significant differences among the evaluated frequencies. These findings should be interpreted with caution due to the limited number of studies and the methodological heterogeneity, which may have reduced statistical power and comparability. CONCLUSIONS: The evidence supports ABR wave I amplitude as a sensitive electrophysiological marker of age-related CS in rodents. Nevertheless, further studies with standardized protocols are needed to strengthen its diagnostic utility and improve comparability across studies.

Animals↗
PubMed2026

Multi-Omics Genome-Wide to Explore the Formation and Development Targets for Intracranial Aneurysms.

Intracranial aneurysms (IAs) represent a significant and potentially life-threatening category of disease, and there is currently a lack of effective treatment options aimed at preventing the progression of the disease. Accordingly, this study is dedicated to exploring and identifying effective drug targets that can help in the prevention of both the formation and rupture of IAs, along with a detailed examination of the underlying potential mechanisms involved in these processes. The data related to IAs for this research was obtained from the ISGC Biobank and UK Biobank. Then, we investigated the possible biological functions and unintended consequences of targeting the specific genes that were highlighted in IAs by using mediation analysis, virtual knockout experiments, and PW-MR studies. A total of 5 unique potential drug targets for IAs (FKTN, MAP3K1, PSMA4, SLC22A4, ADAM17), 4 unique potential drug targets for SAH (PSMA4, ADAM17, GPR160, SLC22A4), and 2 unique potential drug targets for UIA (SLC22A4, PRCP) were identified across brain or blood samples. Among the various candidates identified, SLC22A4 has emerged as a promising potential drug target, showing significant expression levels in both blood and brain tissues. Additionally, phenome-wide MR of SLC22A4 across 32 selected phenotypes did not identify statistically significant adverse associations after FDR correction. Virtual knockout (KO) experiments on SLC22A4 revealed that SLC22A4 KO disrupted 81 genes, all of which are involved in IAs-related pathways. Besides, we recognized BRD-K85337334 as potential candidates for targeting SLC22A4. This research indicates that an increase in SLC22A4 gene expression within the blood or brain is directly linked to a heightened risk of IAs rupture, which will aid in prioritizing the development of drugs for IAs.

Humans↗
PubMed2026

A systematic literature review on low-grade myofibroblastic sarcoma of the trunk.

BACKGROUND: Low-grade myofibroblastic sarcoma (LGMS) is a rare malignant mesenchymal tumor, with primary trunk involvement being particularly uncommon. Due to its rarity, associated diagnostic challenges, and variability in management, a comprehensive evaluation of the available evidence is required. This study aims to systematically review the clinical characteristics, treatment strategies, and outcomes of truncal LGMS. METHODS: A systematic literature search was conducted using PubMed, Web of Science, and Embase for articles published from January 1998 to January 2026. The review included full-text articles involving patients with a pathologically confirmed diagnosis of truncal LGMS. The collected data included patient demographics, tumor features, treatment modalities, recurrence, and follow-up status. RESULTS: Of the 404 studies initially identified, 30 studies involving 59 patients with pathologically confirmed truncal LGMS met the inclusion criteria. Outcome analyses of therapeutic management and clinical course included 45 patients with complete follow-up data, including 42 surgically treated patients and 3 non-surgically managed patients. The final evidence base consisted solely of retrospective studies and case reports. No prospective studies or randomized controlled trials were identified. Consequently, a descriptive statistical analysis was conducted instead of a meta-analysis. CONCLUSION: Current evidence indicates that wide excision with negative margins may be a reasonable primary treatment option for truncal LGMS, with case-based reports showing numerically lower recurrence after wide excision, although the evidence is limited and potentially confounded by multiple factors. Radiotherapy or chemotherapy may be considered only on a highly individualized basis for selected unresectable, recurrent, metastatic, anatomically constrained, or margin-positive cases. Given the very limited sample size and heterogeneous treatment indications across published cases, treatment efficacy cannot be reliably estimated from the available data. Prolonged long-term regular follow-up is recommended for all patients, considering the risk of late recurrence.

Humans↗
PubMed2026

The Impact of Video Game Experience on Surgical Performance: A Systematic Review.

OBJECTIVE: To assess whether video gaming experience is associated with improved surgical performance in the surgeon population across laparoscopic, robotic, and other surgical modalities, and evaluate its implications on surgical training and education. METHODS: A structured literature search was conducted across five databases on 29th November 2024 in adherence to PRISMA guidelines. Comparative studies evaluating surgical performance outcome data between surgeons with differing video game experience were eligible for inclusion. Outcomes evaluated were time to complete task, error rate, accuracy, economy of motion, and overall score. Included studies were assessed for risk of bias using ROBINS-I and RoB 2. RESULTS: 15 studies involving 641 participants were included, comprising one randomized controlled trial and 14 nonrandomized studies. All nonrandomized studies were judged to be at moderate or serious risk of bias, and the single randomized controlled trial was judged to be at serious risk of bias. Differences in study design and outcome measures meant that quantitative synthesis could not be performed. Across laparoscopic studies, video gaming experience was associated with improved overall score and time to task completion predominantly in the period prior to structured training interventions, with accuracy findings consistently favoring gamers in the two studies reporting this outcome. Error rate and economy of motion findings were inconsistent or predominantly nonsignificant. No meaningful association was identified across nonlaparoscopic modalities. CONCLUSIONS: Video gaming may be associated with improved surgical performance in surgeons, though this appears restricted to laparoscopic tasks and the pretraining intervention period. As a low-cost and accessible activity, video gaming may represent a practical informal adjunct to formal surgical training to help ease the transition into structured technical training. Surgical program directors need not alter existing selection criteria or training modules based on the available literature.

Video Games↗
PubMed2026

Simultaneous determination of imiquimod and terbinafine in skin permeation studies: Validation of a liquid chromatography method with fluorescence detection.

Chromoblastomycosis is a chronic, neglected subcutaneous mycosis posing significant therapeutic challenges. A topical strategy combining terbinafine (TBF), an antifungal, with imiquimod (IMQ), a TLR-7/8 agonist immunomodulator, has emerged a promising alternative. However, no validated analytical method is currently available to simultaneously quantify both drugs in skin, which is crucial for novel formulation development. This study reports the development and validation of a simple HPLC method with fluorescence detection (excitation 236 nm, emission 340 nm) for the simultaneous determination of TBF and IMQ extracted from porcine skin. Separation was achieved on a C8 reversed-phase column (125 × 4.0 mm, 5 μm) using a mobile phase of methanol and water (60,40, v/v), both containing 0.1% formic acid at a flow rate of 0.8 mL/min. The method showed excellent linearity (r > 0.999) over 0.01-1.0 μg/mL for IMQ and 0.1-2.0 μg/mL for TBF. Intra- and inter-day precision demonstrated coefficients of variation below 5%, and recovery rates from skin (79-105%) confirmed accuracy. Limits of detection were 0.001 μg/mL for IMQ and 0.004 μg/mL for TBF, with quantification limits of 0.02 μg/mL and 0.16 μg/mL, respectively. This selective, sensitive, and reproducible method represents a valuable analytical tool for supporting the development and quality control of topical formulations for chromoblastomycosis and other fungal skin diseases.

Animals↗
PubMed2025

Quantitative Outcomes for Shared Assessment and Management in Forensic Mental Health: A Meta-Analysis and Systematic Review.

Despite leading models of mental health care encouraging user involvement, users in forensic mental health (FMH) report poor involvement given the difficulty in reconciling shared approaches with risk-averse and legally mandated settings. While previous research has demonstrated qualitative benefits to shared approaches in FMH and has led to a proliferation of self-rated assessment tools, there remains to quantify agreement on self-rated tools and to clarify the impact of shared approaches on care. This meta-analysis examines (1) the correlation between clinician and user ratings, (2) the predictive validity of self-ratings for violence, and (3) the effects of shared risk management on violence and restriction in FMH. Five databases were searched from inception to April 2024, selecting for adult FMH inpatients, shared risk assessment, needs assessment or violence management as interventions, and quantitative outcomes (correlation, agreement, predictive validity, and effect on violence or restriction rates). Fifteen quantitative evaluations were retained. One of three planned meta-analyses could be conducted, with seven records providing paired clinician-user t-tests. Eleven more records provided clinical recommendations on operationalizing shared approaches. Random-effects meta-analysis showed a significant and large paired standard difference of .95 (95% CI = [.49,1.42]) across tools, with significant differences in DUNDRUM-3, DUNDRUM-4, and CANFOR sub-models. While acknowledging between-study heterogeneity, results substantiate quantitative differences where clinicians generally rate more needs and lesser progress than users across tools, showing that self-ratings can and should be used to broach collaborative discussions on needs and progress during FMH treatment. There remains an evidence gap for quantitative benefits in care outcomes and a need to standardize agreement measures for future comparisons and clinical sub-group analyses.

Humans↗
PubMed2026

Screening of Estrogenic and Antiestrogenic Effects of Estradiol, Bisphenol A, and Fulvestrant Using 2D and 3D Breast Cancer Cell Systems With a Luciferase Reporter Gene Assay.

Endocrine-disrupting chemicals (EDCs) like bisphenol A (BPA) pose health risks by interfering with hormones. This study develops and utilizes in vitro 2D and 3D cell models to evaluate the estrogenic and antiestrogenic properties of compounds. Human breast cancer cell lines T47D and MCF7, stably transfected with a luciferase reporter gene (ERE-LUC), were first compared in 2D. Due to the significantly higher sensitivity and responsiveness observed in the T47D line during preliminary 2D screenings, this cell line was exclusively selected for the development of the 3D spheroid model. Cells were treated with 17β-estradiol (E2), BPA, and Fulvestrant (FUL) to assess cell viability and luciferase activity. In 2D models, T47D ERE-LUC cells showed higher responsiveness than MCF7 ERE-LUC, which failed to show significant luciferase induction with E2. In the 3D T47D model, cells exhibited significant and robust changes in luciferase activity in response to E2 and BPA, highlighting the enhanced fidelity of 3D cultures in replicating tissue conditions compared to their 2D counterparts. The study highlights the effectiveness of 3D models over 2D in evaluating estrogenic activity. Specifically, the 3D T47D ERE-LUC system serves as a superior, sensitive, and reliable platform for screening EDCs, offering benefits in cost, data speed, and reduced in vivo reliance.

Humans↗
PubMed2026

Endovascular thrombectomy versus best medical therapy for acute vertebrobasilar artery occlusion in patients with low NIHSS scores: a meta-analysis.

OBJECTIVE: The efficacy of endovascular thrombectomy (EVT) for acute vertebrobasilar artery occlusion (VBAO) presenting with mild symptoms (National Institutes of Health Stroke Scale [NIHSS] score ≤10) remains uncertain. This meta-analysis aimed to compare the effectiveness and safety of EVT versus best medical therapy (BMT) in this population. METHODS: We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to September 2025 for comparative studies. The primary outcome was 90-day excellent functional outcome (modified Rankin Scale [mRS] score 0-1). Secondary outcomes included functional independence (mRS 0-2), symptomatic intracranial hemorrhage (sICH), and all-cause mortality. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects model. RESULTS: Seven observational studies involving 3,107 patients were included. In unadjusted analyses, EVT was associated with a higher rate of excellent functional outcome (OR 2.17; 95% CI 1.58-2.96) but not with functional independence (OR 1.58; 95% CI 0.90-2.77). After adjustment for confounders, EVT was associated with higher rate of excellent functional outcome (OR 2.86; 95% CI 1.89-4.31) and functional independence (OR 1.91; 95% CI 1.01-3.62). Safety outcomes including sICH and mortality did not differ significantly between groups. CONCLUSION: In patients with acute VBAO and mild symptoms, EVT may be associated with superior functional outcomes compared to BMT alone, without a significant increase in procedural risks. These findings suggest a potential role for EVT in selected patients with low NIHSS scores and underscore the need for confirmation in randomized trials.

Humans↗
PubMed2026

Artificial intelligence for anticancer drug discovery from natural products of macroalgae and sponges: A systematic review.

Marine natural products (MNPs) from macroalgae and marine sponges have inspired clinically important anticancer agents, including the cytarabine pharmacophore and the eribulin scaffold, while cyanobacterial dolastatin chemistry supplies the auristatin payloads of several marine-inspired antibody-drug conjugates (ADCs) such as brentuximab vedotin. Artificial intelligence (AI) methods, encompassing both classical machine learning (ML) with hand-engineered features and modern deep learning (DL) with many-layered neural networks, are increasingly supporting key decisions in natural-product anticancer drug discovery, including bioactivity prediction, target identification, absorption, distribution, metabolism, excretion and toxicity (ADMET) filtering, generative analogue design, and the selection of preclinical candidates. DL architectures relevant to this field include graph neural networks, transformer-based molecular generators, diffusion models for protein-ligand docking, and convolutional networks for mass spectrometry, while classical ML contributes interpretable fingerprint-based bioactivity models and molecular networking for dereplication. This review follows a systematic literature review methodology to organize the landscape of AI methods now applied to MNP anticancer discovery, distinguishing ML and DL approaches where relevant, situating them within the chemical context of macroalgal and sponge-derived oncology leads, and critically examining published case studies, including validation level (computational, in vitro, in vivo, clinical). The principal bottleneck for medical translation has shifted partly from algorithmic capability toward data infrastructure and experimental validation. Sparse, heterogeneous, and taxonomically biased bioactivity records limit what current models can learn and reduce the reliability of AI-prioritized candidates entering the preclinical pipeline. A roadmap is proposed that prioritizes open MNP-specific benchmarks, symbiont-aware modeling, and active learning loops with synthesizability and ADMET constraints. These AI workflows may accelerate the prioritization of marine-derived anticancer leads and support earlier, more evidence-based translational decisions in oncology drug development.

Biological Products↗
PubMed2026

Matched targeted therapy use after broad genomic profiling in advanced Non-Small cell lung cancer.

INTRODUCTION: While broad genomic profiling is increasingly used in advanced NSCLC (aNSCLC), the impact of test results on subsequent guideline-concordant targeted therapy selection remains incompletely understood. METHODS: Using a merged dataset of two large, nationwide, patient-level databases, we identified patients who were diagnosed with aNSCLC 2017-2023, had potentially actionable genomic profiling findings, and initiated systemic therapy. Patients were categorized into actionability subgroups based on contemporaneous regulatory approvals and NCCN guideline recommendations. Within each subgroup, we assessed receipt of guideline-concordant targeted therapy within 24 months, including potential underuse (non-receipt of recommended treatment) and overuse (receipt of non-recommended treatment). RESULTS: Among 6620 patients (67.4% ≥65 years, 54.6% female, 68.9% White), guideline-concordant targeted therapy use varied substantially by actionability category: 2313 (89.6%) of 2582 patients with available 1st-line on-label options received them (10.4% underuse), while 212 (67.3%) of 315 patients with available later-line on-label options received them after 1st-line (32.7% underuse). Among 441 patients with available guideline-concordant off-label options, only 122 (27.7%) received them (72.3% underuse). Conversely, 238 (8.6%) of 3282 patients received matched but guideline-discordant off-label options, representing overuse of ineffective or unestablished therapies. Smoking history, squamous histology, and high PD-L1 expression were associated with lower targeted therapy receipt. CONCLUSIONS: In this cohort study of aNSCLC care, the guideline concordance of targeted therapy use varied by clinical actionability of molecular testing results. Underuse was more common in patients with later-line and off-label targeted therapy options. Patients with classical smoking-related risk profiles were substantially less likely to receive targeted therapy even when actionable alterations were identified.

Journal Article↗
PubMed2026

Integrative machine learning and transcriptomic analysis reveals molecular mechanisms underlying low survival rate in larval Chinese Bahaba (Bahaba taipingensis).

Chinese Bahaba (Bahaba taipingensis) is a Class I protected marine fish endemic to China. Low larvae survival during artificial breeding severely hinder population recovery. To investigate the molecular mechanism of high mortality in larval fish, this study performed RNA-seq on liver from naturally deceased (ND) and mass-dead (MD) individuals, combined with least absolute shrinkage and selection operator (LASSO) regression and random forest (RF) algorithms to screen for core signature genes. A total of 873 differentially expressed genes (DEGs) were identified, including 112 upregulated and 761 downregulated genes. GO and KEGG enrichment analyses revealed significant enrichment in amino acid metabolism disorders, one‑carbon folate pool impairment, PPAR signaling abnormalities, ECM-receptor interaction, focal adhesion pathway, indicating widespread metabolic suppression accompanied by extracellular matrix remodeling and signaling disturbances in the livers of MD fish. MAD pre-filtering combined with dual machine learning algorithms yielded 18 robust core signature genes, among which SLC38A4, MMP1, FADD, FKBP5, and APOB were consistently identified as high-frequency core genes by both algorithms. SLC38A4 exhibited the highest importance score in the RF model and was significantly downregulated, making it the primary molecule distinguishing ND from MD phenotypes. ROC curve analysis showed that both models achieved an AUC of 1.000 (95% CI lower bound: 0.610), confirming the precise discriminatory ability of the core genes. GSEA further demonstrated significant enrichment of this core gene set in ND samples. This study provides the first systematic elucidation of the molecular mechanisms underlying liver dysfunction in low survival rate B. taipingensis, characterized by amino acid transport impairment, metabolic reprogramming, and structural remodeling, offering theoretical foundations for health assessment, early mortality risk warning, and artificial breeding conservation of this species.

Animals↗
PubMed2026

Development and Validation of a Predictive Model for Identification of Cognitive Impairment Risk in Older Adults with Subjective Cognitive Decline：A Longitudinal Study.

BACKGROUND: Subjective cognitive decline (SCD) is a transitional state between objective cognitive impairment and cognitively intact mental status, providing a critical window for implementing preventive interventions to delay objective cognitive decline. AIMS: We aimed to develop a predictive model for SCD progression in older adults with mild cognitive impairment (MCI). This model will facilitate the identification of risk factors and establishment of targeted interventions for community-based SCD management. METHODS: Data from the China Health and Retirement Longitudinal Study (CHARLS) was utilized in this study, extracting 18 indicators. Potential predictors selected through univariate Cox regression and LASSO regression analyses were sequentially incorporated into a multivariable Cox regression model. A nomogram was constructed to establish a predictive model. Model validation encompassed Area Under Curve (AUC) metrics for discriminative capacity, complemented by quantitative assessments using calibration curve analysis for precision verification and decision curve analysis (DCA) for clinical utility evaluation. RESULTS: A total of 1099 older adults with SCD were included in the final analysis, of whom 114 (10.3%) developed MCI. Multivariable Cox regression identified residence, marital status, educational level, social participation, gait speed, and baseline cognitive function. The model demonstrated time-dependent AUC values of 0.885, 0.830, 0.839, and 0.836 in the training set when evaluating discriminative capacity at 2-, 4-, 7-, and 9-year, respectively. The predictive model showed excellent predictive ability according to AUC, calibration curve, and DCA. CONCLUSIONS: A predictive model was created to estimate the risk of developing MCI in older individuals with SCD, offering clinician-actionable intervention benchmarks for preventive care.

Humans↗
PubMed2026

Atomoxetine Versus Placebo for Cognitive Deficits in Stimulant Use Disorder: A Systematic Review.

BACKGROUND: Stimulant use disorder (StUD), particularly involving cocaine and amphetamines, is associated with significant cognitive impairments that impede recovery and increase relapse risk. Atomoxetine, a selective norepinephrine reuptake inhibitor, has been proposed as a potential treatment given its role in enhancing executive function and its established efficacy in attention-deficit/hyperactivity disorder (ADHD). This systematic review aimed to evaluate the efficacy, cognitive, and mood effects of atomoxetine compared with placebo in individuals with StUD. METHODS: A comprehensive literature search of PubMed, Cochrane CENTRAL, and Embase databases was conducted to identify randomized controlled trials (RCTs) evaluating atomoxetine for StUD. Eligible studies compared atomoxetine with placebo and assessed outcomes related to cognition (attention and response inhibition), stimulant use or abstinence, mood symptoms, and safety. Data were extracted and synthesized qualitatively due to methodological heterogeneity across studies. RESULTS: Nine RCTs met the inclusion criteria. Findings on cognitive outcomes were inconsistent: Some studies reported improvements in attentional bias and inhibitory control, while others showed no significant effects. Atomoxetine did not significantly reduce stimulant use, craving, or sustain abstinence compared with placebo. Limited mood-related benefits were observed, particularly among male participants, although results were variable. Across studies, atomoxetine was well tolerated, with most adverse events mild and transient. CONCLUSION: Despite a compelling neurobiological rationale and evidence of modest cognitive and mood benefits, atomoxetine has not demonstrated consistent efficacy as a monotherapy for StUD. Its favorable safety profile may warrant further investigation in carefully defined populations, such as individuals with comorbid ADHD or in combination with behavioral interventions.

Atomoxetine Hydrochloride↗
PubMed2026

Fatty acids and breast cancer: Epidemiology, subtype-specific metabolism, immune regulation, and clinical translation.

Fatty acids (FAs) are bioactive dietary and metabolic molecules that participate in membrane architecture, energy homeostasis, inflammatory signaling, gene regulation and immune function, all of which intersect with breast cancer (BC) risk, progression and treatment response. In this narrative review we integrate epidemiological, clinical, translational and mechanistic evidence on the role of FAs in BC. Saturated, monounsaturated, trans- and polyunsaturated FAs (PUFAs) are treated as distinct biological exposures rather than interchangeable measures of total fat intake. Similarly, evidence from dietary assessment, circulating biomarkers, erythrocyte membrane composition, adipose tissue stores and tumor lipid signatures is interpreted separately, because each captures exposure and biology at a different level. BC subtypes differ in FA synthesis, uptake, oxidation, storage and remodeling: luminal tumors are frequently linked to hormone-regulated lipogenesis, human epidermal growth factor receptor 2 (HER2)-positive tumors to growth-factor-driven lipid metabolism, and triple-negative tumors to exogenous FA uptake, inflammatory lipid mediators and ferroptosis-related vulnerabilities. FA-derived mediators also shape immune-cell polarization, cytokine signaling and the tumor microenvironment, and dietary FAs may reshape the gut microbiota; the fiber-derived short-chain FAs it produces, distinct from dietary FAs, likewise help regulate immune and inflammatory tone. Clinical data suggest possible roles for fat-quality modification and selected n-3 PUFA interventions, but findings are heterogeneous and not yet sufficient to support routine biomarker-guided precision onco-nutrition. Candidate biomarkers, such as erythrocyte n-6:n-3 composition, require prospective validation before clinical implementation. FA biology thus represents a modifiable but complex axis in BC prevention, tumor biology and supportive care.

Humans↗
PubMed2026

The future of TCR-Treg therapies is renewables.

Cell therapy has longstanding roots in haematopoietic stem cell transplantation and early immune cell transfers in infectious disease and transplantation, where patient- or donor-derived cells have achieved therapeutic benefit in selected contexts. The modern era has been driven largely by oncology, with engineered modalities such as tumour-infiltrating lymphocytes, CAR-T cells and TCR-engineered T cells delivering transformative responses but requiring complex, costly manufacturing. These platforms are now being adapted for autoimmune diseases to induce durable, antigen-specific immune tolerance, yet broad application is limited by safety concerns, process complexity and access. Non-engineered cell therapies for autoimmunity, including mesenchymal stem cells, polyclonal regulatory T cells and tolerogenic dendritic cells, have shown acceptable safety and proof-of-principle for immune re-education, but clinical responses have been modest and inconsistent, with limited scalability. Engineered approaches such as CAR-T cells can induce reversible B cell depletion in B cell-mediated rheumatic diseases but only addresses antibody-driven pathology and not T cell-mediated autoimmunity. TCR-engineered Tregs have emerged as a promising antigen-specific strategy, offering localized, antigen-linked suppression with bystander tolerance. Preclinical and early clinical data suggest superior potency, stability and disease control compared with polyclonal Tregs at similar or lower doses, but translation is constrained by the rarity and fragility of Tregs and by labour-intensive, CAR-T-like manufacturing. This review highlights emerging solutions for closed, automated and decentralised production, and discusses allogeneic approaches using gene-edited or banked Tregs with HLA engineering or matching. Together, these advances support the development of scalable, "off-the-shelf" TCR-Treg products with potential to provide safe, affordable tolerance-restoring therapies for autoimmune disease.

Humans↗