Search Results (248)

Background: The profile of germline genetic variants among colorectal cancer patients in Panama has not yet been explored. Methods: We recruited 95 patients with colorectal cancer in an Oncology Reference Hospital Unit in the Azuero region of central Panama, which exhibited the highest prevalence of colorectal cancer in Panama. DNA analysis was performed with a panel of 113 genes with germline mutations for cancer (TruSight^® Cancer Sequencing Panel from Illumina, San Diego, CA, USA). Results: Among the 95 cases, 10 pathogenic/likely pathogenic variants (P/LP) were identified in the MUTYH, TP53, CHEK2, PALB2, ATM, and BARD1 genes, representing 10% of the total. The variant 1103G>A (p.Gly368Asp) in MUTYH was the most prevalent. The variant at c.1675_1676delCAinsTG (p.Gln559Ter) in PALB2 is new and is reported for the first time in this study. Variants were most frequently detected in the MUTYH and CHEK2 genes, affecting four and two patients, respectively. Notably, none of the 95 Panamanian patients in the initial colorectal cancer cohort had mutations in mismatch repair (MMR) genes. These genes are among the most frequently mutated in other cohorts around the world. Conclusions: The atypical profile of germline genetic variants in this population may be related to the unique characteristics of the Azuero population in Panama’s central region. This profile may partly explain the high prevalence of colorectal cancer among its inhabitants. Full article

Microsatellite instability (MSI) is a clinically important biomarker for predicting responses to immune checkpoint inhibitors and identifying individuals with Lynch syndrome. Although MSI detection has been incorporated into Illumina’s next-generation tumor sequencing workflows, interpretation of the results remains challenging due to the absence of standardized thresholds and reporting criteria. In this retrospective study, we assessed the performance of MSI detection using Illumina’s targeted NGS panels—TruSight Tumor 170 and TruSight Oncology 500. The NGS-based MSI results were compared to those obtained by the reference method, MSI-PCR, across multiple tumor types in a real-world cohort of 331 cancer patients. The NGS method demonstrated high concordance overall (AUC = 0.922), though sensitivity was lower in colorectal cancers (AUC = 0.867) due to broader score variability and overlapping distributions. Our findings support the clinical utility of Illumina’s NGS-derived MSI scores for identifying MSI-H tumors, with a recommended MSI score cut-off value of ≥13.8%. Additionally, a borderline group was introduced, defined by an MSI score ranging from ≥8.7% to <13.8%. Within this range, the integration of TMB into the MSI classification workflow significantly improves diagnostic accuracy. For samples that remain inconclusive, orthogonal confirmation using MSI-PCR is advised to ensure accurate MSI classification. Full article

Thyroid cancer (TC) is the most common endocrine malignancy, with a rising global incidence. In Ecuador, TC rates are among the highest worldwide. Generally, fine-needle aspiration (FNA) remains the standard diagnostic tool; however, due to its limitations, alternative or complementary approaches are required. In this context, liquid biopsy, particularly circulating tumor DNA (ctDNA), offers a promising, minimally invasive option for tumor genotyping. Objective: This study evaluated the concordance between genetic variants identified in ctDNA and tumor tissue. Thirty-six women with papillary thyroid cancer were included. Tumor tissue and blood samples were collected, and DNA was extracted. Next-Generation Sequencing (NGS) using the TruSight Tumor 15 panel identified genetic variants in both ctDNA and tumor DNA. Variant pathogenicity was assessed following ACMG guidelines. Genetic ancestry was determined using Ancestry Informative Markers (AIMs). A total of 71 cancer-associated variants were detected, with 81.69% concordance between tumor DNA and ctDNA. TP53 was the most frequently mutated gene. While most pathogenic variants were found in tumor tissue, some variants appeared exclusively in ctDNA samples on specific patients, suggesting tumor heterogeneity. Ancestry analysis revealed a predominant Native American component (62.4%). Liquid biopsy demonstrates high concordance with tumor tissue analysis and holds potential as a complementary diagnostic tool for thyroid cancer. However, challenges such as low ctDNA yield and underrepresentation in genetic databases highlight the need for improved protocols and increased inclusion of admixed populations in genomic studies. Full article

The aim of this work was to improve the technology for obtaining coating based on plasticized polylactide from its aqueous suspensions. For this purpose, a film formation process with additional heating was developed, and the influence of plasticizers on the film-formation temperature was investigated. It is shown that using only mechanical emulsification, it is possible to obtain a material with an average particle size of 2.4 microns, which is suitable for further research and modification for film materials. The introduction of epoxidized fatty acids (oleic and linolic) was found to reduce the film-formation temperature by 20–30 °C compared to the unplasticized polymer, which puts them on par with the classical plasticizer, polyethylene glycol, reducing the film-formation temperature by 36% at the same concentration. Full article

In the environment, plastic waste degrades into small particles known as microplastics and nanoplastics (MNPLs), depending on their size. Given the potential harmful effects associated with MNPL exposure, it is crucial to develop environmentally representative particles for hazard assessment. These so-called true-to-life MNPLs are generated through in-house degradation of real-world plastic products. In this study, we produced titanium-doped nanoplastics (NPLs) from opaque polyethylene terephthalate (PET) milk bottles, which contain titanium dioxide as a filler. The resulting PET(Ti)-NPLs were thoroughly characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), mass spectrometry (MS), dynamic light scattering (DLS), ζ-potential measurements, transmission electron microscopy (TEM), and Fourier-transform infrared (FTIR) spectroscopy. Human-derived THP-1 monocytes were employed to investigate particle uptake kinetics, dosimetry, and genotoxicity. A combination of flow cytometry and inductively coupled plasma mass spectrometry (ICP-MS) enabled the quantification of internalized particles, while the comet assay assessed DNA damage. The results revealed dose- and time-dependent effects of PET(Ti)-NPLs on THP-1 cells, particularly in terms of internalization. Titanium doping facilitated detection and influenced genotoxic outcomes. This study demonstrates the relevance of using environmentally representative nanoplastic models for evaluating human health risks and underscores the importance of further mechanistic research. Full article

Introduction: Computed tomography-guided biopsies (CTGB) are essential in diagnosing various conditions, particularly in respiratory medicine, with lung cancer being a primary focus. A significant complication associated with CTGB is pneumothorax, which can occur in up to 26% of cases. At Northumbria Healthcare NHS Foundation Trust, a large interventional service collaborates closely with radiologists and respiratory physicians. This study aims to evaluate the incidence of pneumothorax following CTGB. Methods: A retrospective service review was conducted on all lung parenchymal CTGBs performed between April 2011 and July 2023, with approval from the local information governance. Demographic data and clinical outcomes were analyzed using descriptive statistics. Continuous variables are presented as medians with interquartile ranges (IQR), while categorical variables are reported as frequencies and percentages. Results: A total of 1492 CT-guided lung biopsies were analyzed. The median age of patients was 72 years (IQR 10.5), and 50.9% were male. Pneumothorax occurred in 23.8% (n = 355) of cases. Of these, 159 (44.8%) were detected on post-biopsy CT scans. The average number of pleural passes was 1.8 (range 1–4). Among those with pneumothorax, 53.6% had radiologically evident emphysema. The median forced expiratory volume in 1 s (FEV1) was 1.97 L (IQR 1.04). Sixty-seven percent (n = 234) of patients had no pleural contact, and the median lesion size was 26 mm (IQR 24). Seventy-two percent (n = 255) of lesions with pneumothoraces were less than 3 cm deep. Forty-four percent of biopsies were performed using 18 French gauge tru-cut needles. Of the 355 pneumothoraces, 89% (n = 315) were managed conservatively, with 42 requiring pleural intervention (41 small-bore 12 Fr intercostal chest drains and one pleural vent). Symptoms were initially present in 40 cases, and two cases developed symptoms up to 7 days post-procedure. Conclusions: The incidence of pneumothorax is consistent with expected rates, with more occurrences observed in biopsies of smaller lesions lacking pleural contact, lesions with surrounding emphysema, and cases requiring multiple pleural passes. FEV1 does not appear to influence the risk of pneumothorax. Conservative management is generally effective, without significant complications. Full article

Prostate cancer is the most commonly diagnosed malignancy in men and continues to be a leading cause of cancer-related mortality. Accurate and timely diagnosis is essential for distinguishing clinically significant tumors from indolent lesions and for informing treatment decisions. Multiparametric magnetic resonance imaging (mpMRI) has revolutionized prostate cancer detection by enabling precise lesion localization, risk stratification, and improved biopsy targeting. Fusion biopsy, which combines mpMRI findings with real-time transrectal ultrasonography (TRUS), has emerged as a highly effective method for sampling suspicious lesions. This review provides an integrated anatomical, epidemiological, technical, and clinical overview that highlights the evolving role of fusion biopsy in contemporary prostate cancer diagnostics. We also explore emerging strategies such as penumbra-targeted sampling, discuss ongoing clinical challenges, and examine the impact of biopsy underestimation and lack of standardization. Compared to conventional systematic biopsy, mpMRI-TRUS fusion biopsy improves the detection of clinically significant prostate cancer while reducing the overdiagnosis of low-risk tumors. To our knowledge, few recent reviews have comprehensively synthesized current clinical guidelines, emerging biopsy techniques, and future directions within a single narrative. mpMRI-TRUS-guided fusion biopsy represents a major advancement in the prostate cancer diagnostic pathway, promoting precision oncology by reducing overtreatment and facilitating individualized patient care. This review aims to assist clinicians in adopting biopsy innovations that enhance diagnostic accuracy and improve patient outcomes. Full article

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a growing health concern worldwide. Human cell-based in vitro culture models that retain disease-relevant phenotypic pathways and responses to assess the efficacy and liability of new therapeutics are needed. Obeticholic Acid (OCA), a Farnesoid X Receptor agonist, has been identified for MAFLD treatment, and clinically shown to have anti-inflammatory and anti-fibrotic effects. In this study, healthy and disease-origin primary human hepatocytes (PHHs) were cultured in TruVivo^®, an all-human hepatic system for 14 days and treated with OCA to determine its’ effects on lipogenic, inflammatory, and fibrogenic pathways. Decreases in lipogenesis and triglyceride levels were measured in OCA treated healthy and diseased PHHs. Significant decreases in CYP3A4 activity and gene expression were quantified. Macrophage marker expression, pro-inflammatory cytokines and fibrotic markers were lowered in OCA treated diseased PHHs. CYP7A1 gene expression decreased, while BSEP gene expression increased in OCA treated healthy and diseased PHHs. Overall, OCA treatment reduced lipogenic, inflammatory, and fibrogenic markers in diseased PHHs. Differences in the potency and efficacy of OCA against different disease-relevant pathways were observed in healthy and diseased PHHs indicating divergence of key regulatory mechanisms between healthy versus diseased phenotypes. Full article

Background: Aesthetic dentistry increasingly demands minimally invasive, predictable, and patient-centered solutions. Digital technologies and AI-driven planning tools are now integral to interdisciplinary treatments. Aim: To evaluate, by means of a 16-item questionnaire, patients’ perceptions of smile aesthetics and oral function before and after receiving clear aligner therapy followed by minimally invasive ceramic veneers, using digital planning and Smile Creator software. Materials and Methods: Five adult patients underwent digital smile design, clear aligner therapy, and feldspathic veneer placement. Pre- and post-treatment perceptions of smile aesthetics and function were assessed using a structured questionnaire. AI-based simulation tools (2D and 4 K TruSmile video previews) were incorporated. Paired t-tests were used to compare outcomes before and after treatment. Results: Mean pre-treatment scores were 4.8 for smile aesthetics and 6.6 for function. Post-treatment scores significantly improved to 9.8 (p = 0.001) and 9.4 (p = 0.002), respectively. Patients rated AI-generated smile previews more favorably than 2D designs and acknowledged the value of digital tools in understanding and accepting treatment. Conclusions: The integration of digital and AI-based tools in aesthetic dentistry enhances patient communication, improves predictability, and enables minimally invasive treatment. Patient satisfaction was high, underscoring the effectiveness of the combined orthodontic and prosthetic approach. Full article

Weight traits serve as key economic indicators for assessing growth performance and commercial quality in the mud crab Scylla paramamosain, yet the genetic basis of these traits remains poorly characterized. Here, we performed whole-genome resequencing on 323 individuals and conducted genome-wide association studies (GWAS) on five weight-related traits: (1) body-related traits, including body weight (BW), trunk weight (TruW), and weight excluding chelae (WEC); (2) appendage-related traits, containing appendage weight (AppW) and cheliped weight (CheW). Significantly associated SNPs were primarily enriched on chromosomes 15, 22, 25, and 36. For body-related traits, we identified 45 shared candidate SNPs and 175 common candidate genes; appendage-related traits revealed 71 shared candidate SNPs, and 229 common genes were identified; and across all five traits, there were 9 shared candidate SNPs and 49 common genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that shared functional terms/pathways among the five traits were mainly related to metabolism, development, and immunity. Body-related traits exhibited more unique GO terms and KEGG pathways associated with metabolism and immunity, whereas appendage-related traits showed some unique GO terms and KEGG pathways involved in development and morphogenesis. Among the candidate genes, we identified multiple genes associated with growth and development, metabolism, and immune responses. For example, the CCHa1R gene, common to carapace-related traits, is linked to feeding; the DCX-EMA gene, which is common to appendage-related traits, is connected to movement, and the MSTO1 gene is pertinent to muscle development. Among the candidate genes shared by all five traits, there are a series of genes concerning growth and development (such as NVD, CYP307A1, FGF1, NF2, ANKRD52) and immune responses (RGS10). These findings advance our understanding of the genetic architecture underlying decapod crustacean growth and provide valuable insights for optimizing sustainable breeding strategies in S. paramamosain. Full article

Background/Objectives: Focal therapy (FT) for prostate cancer (PCa) is an alternative to radical treatments that aims to balance cancer control and quality of life preservation in well-selected patients. Understanding its general principles and outcomes is key for its widespread adoption and proper implementation. Methods: The International Consultation on Urological Diseases nominated a committee to review the literature on FT for PCa. A comprehensive PubMed search was conducted to identify articles focused on the different aspects of FT, including patient selection, imaging techniques, treatment modalities, cancer control and safety outcomes, integration with other approaches and future perspectives. Results: FT for PCa was introduced in the 1990s with cryotherapy and high-intensity focused ultrasound (HIFU) as pioneering modalities. Though initially guided by transrectal ultrasound (TRUS) and large biopsy templates, FT implementation expanded significantly with the advent of multiparametric magnetic resonance imaging (MRI) and the validation of the index lesion concept. Appropriate patient selection is key for FT and relies on prostate-specific antigen (PSA) metrics, MRI findings and targeted biopsy information. Multiple energy sources are now available, each with specific technical characteristics. Cancer control rates vary by energy modality, tumor characteristics, and institutional experience, demonstrating comparable outcomes to radical treatments in well-selected patients. The safety profile is excellent, with high rates of urinary continence and sexual function preservation. Post-treatment surveillance integrates PSA measurements, imaging, and histological assessment. Future directions for further FT adoption include the availability of long-term data, protocol standardization and technological improvements to enhance patient selection and treatment planning and delivery. Conclusions: FT is a valuable therapeutic option for selected patients with localized PCa, demonstrating promising oncological outcomes and better functional preservation compared to radical treatments. Understanding its principles and technical aspects is essential for offering comprehensive PCa care. Full article

We aim to investigate the role of the Herpesviridae family (HHV) in the onset and progression of prostate cancer (PCa) and to profile the local PCa immunological status. A total of 116 “tru-cut” biopsies (58 PCa and 58 benign prostatic hyperplasia [BPH]) and 49 formalin-fixed paraffin-embedded (FFPE) instances of PCa were analysed using real-time qPCR and histological examination. Infection with CMV, EBV, HHV6, and HHV7 was detected in 11.5% of the “tru-cut” biopsies (25.9% in BPH and 6.9% in the PCa group). In the formalin-fixed paraffin-embedded (FFPE) samples, infection was detected in 69.4% of the patients, with individual rates of EBV (47%), HHV6 (38%), HHV7 (41%), CMV (2.9%), HSV2 (2.9%), and VZV (5.8%). In the HHV-infected PCa cases, the histopathological landscape included intratumor lymphocyte infiltration with fibrosis and necrosis, periductal chronic inflammatory reaction and granulomatous lesions with foci of abscesses and necrosis, as well as inflammatory infiltration, chronic lymphadenitis, prostatic intraepithelial atrophy (PIA), and high-grade prostatic intraepithelial neoplasia (HGPIN). The majority of HHV-infected PCa patients were predominantly classified as grade G3/G4/G5 tumours, exhibiting perineural, perivascular, and lymphovascular invasion, seminal vesicle invasion, senile vesicle amyloidosis, and lymph node metastasis. Statistical analysis demonstrated a significant association between HHV infection and PCa (χ² ≈ 20.3, df = 1, p < 0.0001; Fisher’s exact test, p < 0.0001) with an odds ratio of 6.50 (95% CI: 2.80–15.12). These findings suggest that long-term HHV infection could contribute to a complicated and potentially altered immune PCa tumour environment due to inflammation. This may serve as a predictor of aggressive disease progression. Full article

The biocompatibility and long-term stability of stainless steel orthodontic devices are critically influenced by their corrosion resistance in the oral environment. This study evaluates the effect of three artificial saliva formulations—Afnor (pH 7.64), Fletcher (pH 8.07, fluoride-containing), and Fusayama/Meyer (pH 6.34, acidic)—on the surface integrity and chemical behavior of 316L stainless steel over 7 and 28 days. A multi-technique approach was employed, including SEM imaging, EDX elemental mapping, XRF analysis, microhardness testing (Vickers), and the monitoring of key physico-chemical parameters (pH, conductivity, salinity, and TDS). The results indicate that Afnor saliva maintains alloy stability with minimal surface damage while Fusayama/Meyer promotes pitting corrosion and selective leaching of Fe and Ni. Fletcher saliva led to the formation of crystalline corrosion products and significant surface hardening, likely due to the interaction of fluoride with the passive layer. Microhardness values increased across all samples after 28 days, most notably in the Fletcher condition (from 191.3 HV to 256.9 HV). These findings provide valuable insights into the time-dependent degradation mechanisms of orthodontic stainless steel in varied salivary environments, emphasizing the importance of simulating realistic oral conditions in corrosion testing. The study contributes to the optimization of material selection and surface treatment strategies for improved biocompatibility in dental applications. Full article

Objective: To evaluate the safety, adequacy, and accuracy of tru-cut biopsy of gynaecologic tumours in a population of Czech women. Methods: A four-year retrospective study of ultrasound-guided tru-cut biopsy of gynaecologic tumours was conducted in the Department of Obstetrics and Gynaecology, Charles University, Hradec Kralove, Czech Republic. Results: One hundred and four women with gynaecologic tumours underwent transvaginal tru-cut biopsy within the study period. The most common indication for tru-cut biopsy in more than one-half of the women was a suspicion of malignancy/inability to exclude malignancy (59, 56.7%). Most of the tumours were malignant on histopathological examination (71, 68.3%), with advanced ovarian cancer being the most common type of malignancy (43/71, 60.6%). The overall adequacy and accuracy rates of tru-cut biopsy were 93.3% and 93.3%, respectively. Most of the inadequate samples were obtained from overweight and obese women (5/7, 71.4%), with only one biopsy sample taken in the majority of the inadequate biopsies (5/7, 71.4%). Accuracy was higher for malignant than benign tumours (97.7% vs. 82.4%). For malignant tumours, accuracy was highest for advanced ovarian cancers (33/40, 82.5%). Only one case was complicated by bleeding, giving an overall complication rate of 1%. The complicated biopsy was taken by a gynae-oncology trainee. Conclusions: Tru-cut biopsy is a cost-effective and safe preoperative diagnostic modality for patients with gynaecologic tumours, offering high adequacy and accuracy. It is particularly useful in patients with advanced ovarian cancer, most of whom present late with inoperable tumours that contraindicate primary surgery. Full article

While locally advanced rectal cancer is the first clinical suspicion for severe rectal stenosis, in extremely unusual cases a lower bowel obstruction may be related to bladder metastasis. We present the case of a 64-year-old male who was admitted for occlusive rectal tumor (4 cm from the anal verge), for which an emergency loop-colostomy was performed. After two inconclusive endoscopic biopsies, a transanal rectal tru-cut biopsy allowed for the detection of high-grade urothelial carcinoma with signet ring cells. Furthermore, primary origin was detected in a small bladder tumor. In imaging reassessment after neoadjuvant chemotherapy, regression of the lesions both from the bladder and rectum was observed. Radical surgery with total pelvic exenteration was considered in the absence of other secondary tumors, but the patient declined and continued with radiotherapy. Subsequently he developed malignant chylous ascites and unfortunately died three months later. Reviewing the literature, we found twenty-five cases of urothelial metastasis to the rectum, originating from the bladder, including this newly present case. Rectal metastasis of urothelial origin poses a two-fold challenge in terms of both diagnosis and treatment. Determining the specific features of this uncommon manifestation of a common disease will improve future approaches. Full article