Medical sciences (Basel, Switzerland)最新文献

Background: Autism spectrum disorder (ASD) is associated with distinct visual attention patterns that provide insight into underlying social-cognitive mechanisms. Methods: This systematic review (PROSPERO: CRD42023429316), conducted per PRISMA guidelines, synthesizes evidence from 14 peer-reviewed studies using eye-tracking to compare oculomotor strategies in autistic children and typically developing (TD) controls. A comprehensive literature search was conducted in PubMed, Web of Science, and Science Direct up to March 2025. Study inclusion criteria focused on ASD versus TD group comparisons in individuals under 18 years, with key metrics, fixation duration and count, spatial distribution, saccadic parameters systematically extracted. Risk of bias was assessed using the QUADAS-2 tool, revealing high heterogeneity in both index tests and patient selection. Results: The results indicate that autistic children exhibit reduced fixation on socially salient stimuli, atypical saccadic behavior, and more variable spatial exploration compared to controls. Conclusions: These oculomotor differences suggest altered mechanisms of social attention and information processing in ASD. Findings suggest that eye-tracking can contribute valuable information about heterogeneous gaze profiles in ASD, providing preliminary insight that may inform future studies to develop more sensitive diagnostic tools. This review highlights visual attention patterns as promising indicators of neurocognitive functioning in ASD.

Purpose: Stress urinary incontinence (SUI) is a significant medical challenge affecting substantial parts of modern societies. Several studies suggested that cell therapy may alleviate the symptoms. However, in many cases, the overall efficacy was not satisfactory for the patient's needs. Moreover, in our recent preclinical studies, myoblasts isolated from M. semitendinosus failed to restore significant urethral sphincter function. We, therefore, investigated in our large animal SUI model whether myoblasts from other muscles yielded better sphincter recovery. Methods: Urethral sphincter deficiency was induced surgically in six female littermates and confirmed by measuring the urethral wall pressure. Three days after induction of sphincter deficiency in gilts, homologous myoblasts were injected into the sphincter complex. The urethral wall pressure and urine status were monitored weekly for a six-week follow-up. Results: Myoblasts isolated from M. extensor carpi radialis yielded a high expression of the myogenic markers desmin, CD56, ACTA1, MSTN, Myf6, and MyoD; were differentiation-competent; and formed myotubes in vitro. Such cells restored significant sphincter deficiency (2494 ± 266 U; ≙92%; p < 0.001; n = 6) and yielded a complete functional recovery from the induced sphincter deficiency (481 ± 123 U, ≙18%) when compared to the starting levels of untreated healthy pigs (2683 ± 764 U; ≙100%). The experimental group showed significant recovery compared to the mock controls (p < 0.045). Conclusions: The choice of myoblasts contributes to the clinical outcome in our large animal model of urinary incontinence. Myoblasts from M. extensor carpi radialis facilitated better sphincter recovery compared to myoblasts from M. semitendinosus.

Background: Preoperative inflammatory and nutrition-related markers-including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score-have shown prognostic relevance in various malignancies. However, their comparative utility in predicting recurrence and survival across clinically relevant subgroups in patients with intrahepatic cholangiocarcinoma (iCCA) undergoing curative-intent resection remains unclear.

Methods: This retrospective study included 213 patients with histologically confirmed iCCA who underwent curative-intent resection between 2015 and 2021. Preoperative NLR, LMR, PNI, and CONUT scores were calculated from laboratory data obtained within one week before resection. Clinicopathological variables, recurrence, and survival outcomes were analyzed using Cox regression and Kaplan-Meier methods.

Results: A preoperative NLR ≥ 2.4 was independently associated with poorer DFS (HR = 1.66, p = 0.025) and OS (HR = 1.94, p = 0.006). This effect remained significant in patients with R0 resection (DFS: HR = 1.66, p = 0.004; OS: HR = 2.11, p = 0.014) and in those who subsequently developed recurrence (OS: HR = 1.83, p = 0.004). The CONUT score was correlated with OS in both R0 and recurrent subgroups. Tumor morphology, consistent with prior reports, was identified as a postoperative pathological factor associated with worse prognosis.

Conclusions: Preoperative NLR was associated with poorer DFS and OS in iCCA patients undergoing curative-intent resection. This association was consistently observed in subgroups with R0 resection and in those who developed recurrence. Meanwhile, the CONUT score showed limited independent significance only among patients with R0 resection who experienced recurrence.

Background: Retinitis Pigmentosa (RP) is a group of inherited retinal dystrophies with significant genetic heterogeneity. The prevalence and clinical characteristics may vary among different populations due to genetic and cultural factors.

Objective: To analyze the clinical characteristics, demographic distribution, and genetic factors of RP patients in this cohort of 95 Turkish RP patients.

Methods: This retrospective study analyzed data from 95 RP patients collected through structured questionnaires and clinical records. Data included age of symptom onset, family history, consanguineous marriage history, visual acuity, and genetic test results.

Results: The mean patient age was 36.0 ± 12.6 years (range: 13-71 years). Mean symptom onset age was 14.8 ± 11.1 years (range: 0-52 years). Positive family history was present in 53.1% (43/81) of evaluable patients. Consanguineous marriage history was found in 52.4% (43/82) of cases. Among patients with visual acuity data (n = 21), 85.7% had severe vision loss (≤10%), 4.8% had moderate vision loss (11-30%), and 9.5% had mild vision loss (>30%). Genetic testing was performed in 54.3% of patients, with CERKL and USH2A being the most commonly identified genes.

Conclusions: This cohort of 95 Turkish patients with RP shows predominant autosomal recessive inheritance patterns with high rates of consanguineous marriage and positive family history. The majority of patients present with severe vision loss, and symptoms of onset typically occur during childhood and adolescence. These findings highlight the importance of genetic counseling and early diagnosis strategies in populations with high consanguinity rates.

Cell line misidentification, first exposed when HeLa cells were shown to contaminate dozens of "unique" cultures, now compromises roughly one in five lines and renders thousands of papers potentially unreliable, propagating unreliable data through hundreds of thousands of citations. The financial fallout is vast with irreproducible research linked to faulty cell stocks costing the United States an estimated $28 billion each year. Today, authentication is rapid, cheap and highly accurate. Modern 24-plex short tandem repeat (STR) kits, analyzed by six-dye capillary electrophoresis and benchmarked against public databases, verify a culture in half a day for less than €40, lowering the probability of mistaken identity to less than 10-15. Complementary SNP panels, low-pass genome sequencing, digital PCR and nascent methylation "age clocks" close remaining blind spots such as aneuploidy or mixed-species co-cultures. Monte-Carlo modeling shows that even at a contamination risk of 0.07% routine STR testing yields a five-year return on investment above 3000% for a mid-size lab. Reflecting this evidence, ANSI/ATCC standards, NIH and Horizon Europe grants, major journals and FDA/EMA guidelines now encourage, recommend, or make authentication mandatory. This review discusses the historical roots and economic losses resulting from cell misidentification and contamination and offers a pragmatic roadmap to prevent working with falsified cell lines. It is further discussed that FAIR-compliant data archiving and integration of STR workflows into laboratory data management systems will allow laboratories to shift from sporadic testing of cell quality to continuous, artificial intelligence-supported assessments.

Background: Sodium glucose co-transporter-2 (SGLT-2) inhibitors are antihyperglycemic drugs used in type 2 diabetes mellitus management, and they have associated cardiovascular and renal advantages beyond their glucose-lowering effects, with maintained proof linking gut microbiota modulation to their multiple therapeutic benefits. Aim: This review aims to deliver an overview of the current knowledge regarding the relationship between SGLT-2 inhibitors and the gut microbiota and how this interplay impacts the gut-organ axes such as the lung, heart, brain, liver, and hematological system. Methodology: A literature review was performed in Web of Science, PubMed, and Google Scholar to discover studies that assessed the effects of SGLT-2 inhibitors on gut microbiota composition, microbial metabolites, and associated systemic consequences. Results: SGLT-2 inhibitors modulate gut microbiota and its driven metabolites, strengthening the barrier integrity and alleviating endotoxemia, inflammation, and oxidative stress, resulting in beneficial outcomes across the different gut-organ axes. Conclusion: Gut microbiota modulation is an emerging approach in mediating the multifaceted beneficial impacts of SGLT-2 inhibitors, revealing that their effectiveness goes beyond glycemic control. Future research should concentrate on the microbial taxa and metabolites that mediate these impacts and testing combination approaches that target SGLT-2 pathways and gut microbiota to enhance preservation of different organs.

Background/Objectives: Stemness has been proposed as a unifying driver of invasion, treatment resistance, and relapse in oral squamous cell carcinoma (OSCC). We synthesized two complementary evidence streams to determine whether higher stemness predicts poorer survival in OSCC: (i) computational stemness signatures derived from transcriptomic/epigenetic data and (ii) tissue cancer stem cell (CSC) immunophenotypes by immunohistochemistry (IHC). Methods: Following PRISMA 2020, we searched PubMed/MEDLINE, Embase, Scopus, and SciELO. Adults with histologically confirmed OSCC were eligible. Primary outcome was overall survival (OS); disease-specific survival (DSS) and recurrence-free survival (RFS) were secondary. Two parallel meta-analyses pooled effects within domains; random-effects restricted maximum likelihood (REML) models were applied. Results: Of 785 records, 11 studies met criteria. For computational signatures (k = 6), higher stemness was associated with poorer OS (pooled HR 2.24, 95% CI 1.61-3.12; I² ≈ 49%). Sensitivity excluding the single unadjusted Kaplan-Meier (KM)-derived estimate yielded a similar effect (HR 2.13, 95% CI 1.56-2.89). For CSC-IHC (main analysis, k = 2), CSC-positive profiles predicted worse OS (pooled HR 2.01, 95% CI 1.42-2.84; I² ≈ 0%); results were robust to excluding an internally inconsistent study (single-study HR 2.078). An exploratory sensitivity analysis, including a 1-year HR (different time horizon), increased heterogeneity and was not considered definitive. A functional meta-synthesis converged on epithelial-mesenchymal transition/extracellular matrix remodeling, hypoxia/glycolysis, redox/ferroptosis resistance, and ribosome/rRNA biogenesis, supporting biological plausibility across modalities. Conclusions: Across computational and IHC evidence, stemness consistently portends inferior OS in OSCC, offering a biologically anchored framework for risk stratification and testable therapeutic hypotheses.

Background: Small renal masses (SRMs) are increasingly prevalent. Percutaneous renal biopsy (PRB) is usually reserved for diagnosis of benign renal disease or secondary metastatic disease. SRMs are frequently benign or of low malignant potential. Invasive treatment may result in significant morbidity. Current literature supports the use of PRB in diagnostic assessment of SRMs. We aim to assess the rates of PRB in Australia since its introduction in the Medicare Benefits Scheme (MBS).

Methods: Data regarding PRBs for the period between January 2000 and December 2024 were extracted from the MBS. Paediatric patients aged <15 years were excluded. Population-adjusted incidences were calculated using publicly available demographic data.

Results: A total of 31,870 PRBs were performed between 2000 and 2024, with an average year-on-year increase of 0.24 PRBs per 100,000 persons per year (95% CI: 0.21-0.27) and an absolute increase of 4.9 PRBs per 100,000 persons. Males had higher PRB rates than females (mean difference: 2.73 per 100,000/year). The largest rise was in NSW, increasing by 13.6 per 100,000, with similar increases in VIC and QLD (4.9 and 2.8 per 100,000, respectively). SA, TAS, and ACT experienced significant reductions (5.7, 3.5, and 6.0 per 100,000, respectively). There was significant inter-state heterogeneity (p < 0.001). PRB rates were highest among the 55-74 and ≥75 age groups. The PRB:nephrectomy ratio increased significantly (0.02/year; 95% CI: 0.016-0.024).

Conclusions: The consensus supporting PRBs for SRMs is reflected in Australia. However, there remains significant heterogeneity between demographic groups. Further work is necessary to ensure standard-of-care treatment accessibility to prevent overtreatment.

Background: Adoptive cell therapy using genetically engineered recombinant T cell receptors (rTCRs) expressed in T cells (TCR-T cell therapy) provides precision targeting of cancer cells expressing tumor-associated or tumor-specific antigens recognized by the rTCRs. Standardized analytical tools are lacking to easily quantify receptor expression.

Methods: To overcome this hindrance, a universal tagging system (UniTope & TraCR) was designed consisting of a minimal peptide epitope (UniTope) inserted into the constant region of the rTCR α or β chain and a high-affinity monoclonal antibody (TraCR) specific to this tag. Detailed biophysical, biochemical, and functional assays were performed to evaluate rTCR expression, folding, pairing, and antigen recognition, as well as antibody performance, using the UniTope & TraCR System.

Results: Tagged rTCRs were stably expressed in human T cells with surface densities comparable to untagged rTCRs. The TraCR antibody bound UniTope with nanomolar affinity and no detectable cross-reactivity was observed for endogenous proteins expressed by human cells of diverse origin, importantly, including T cells of the natural T cell repertoires of multiple human donors. Functional assays confirmed that UniTope-tagged rTCRs preserved their antigen-specific cytokine secretion and cytolytic activity upon antigen-specific stimulation. The UniTope & TraCR System enabled robust detection of rTCR-expressing T cells by flow cytometry, and rTCR protein expression by Western blot or immunoprecipitation, supporting the quantitative assessment of receptor copy number and structural integrity.

Conclusions: The UniTope & TraCR System provides a modular, construct-agnostic platform for monitoring engineered rTCRs, integrated into TCR-T cell therapies currently in development.

Background/Objectives: Since 1988, the IARC has classified alcohol as a type 1 carcinogen, causally linked to seven types of cancer (oral cavity, pharynx, larynx, esophagus, colorectum, liver and breast carcinomas). Several agencies, such as the WHO and the IARC, hold that there is a direct monotonic association between any gram of alcohol consumed and the risk of cancer, regardless of the drinking pattern. On the other hand, an expanding body of evidence indicates that drinking pattern may substantially modify the effect of alcohol consumption. The Mediterranean alcohol-drinking pattern (MADP) includes different aspects of alcohol consumption, such as preference for red wine, moderate alcohol consumption with meals, spreading consumption over the week and avoiding binge drinking. Conformity to this pattern has shown inverse associations with all-cause mortality, cardiovascular disease and diabetes. However, its relationship with cancer incidence has not been studied yet. Our objective was to assess how alcohol consumption patterns, with particular emphasis on the MADP, relate to the incidence of the seven alcohol-related cancers. This information is needed to support cancer prevention recommendations that may go beyond the amount of alcohol consumed to also include the drinking pattern. Methods: We prospectively followed 19,541 participants in the SUN ("Seguimiento Universidad de Navarra") cohort for a median of 13.8 years. We classified participants into four groups, namely, abstainers and three further groups according to their adherence to the MADP score (low, moderate and high). Results: A substantial reduction in the risk of alcohol-related cancer incidence was observed only in men for high versus low adherence to the MADP, with an adjusted hazard ratio (HR) of 0.44 (95% confidence intervals (CIs) (0.21-0.92)). The category of moderate adherence to the MADP showed a lower risk of cancer incidence with a tendency towards statistical significance (HR = 0.56, 95% CI, 0.30-1.06). For women, no result reached statistical significance. Conclusions: Based on the available evidence, separate messages by sex should be delivered. In men, the association between alcohol and cancer goes beyond the amount of alcohol consumed, and a Mediterranean drinking pattern may be beneficial even for alcohol-related cancers. Men should, therefore, receive an additional message: among alcohol consumers, greater adherence to the MADP may help lower their risk of developing alcohol-related cancers. No benefit is supported for the MADP against alcohol-related cancers in women.