Raman spectroscopy in lung cancer diagnostics: Can an in vivo setup compete with ex vivo applications?

Lung carcinoma remains the leading cause of cancer death worldwide. The tactic to change this unfortunate rate may be a timely and rapid diagnostic, which may in many cases improve patient prognosis. In our study, we focus on the comparison of two novel methods of rapid lung carcinoma diagnostics, label-free in vivo and ex vivo Raman spectroscopy of the epithelial tissue, and assess their feasibility in clinical practice.

Endometrial stromal tumor with whorling and GREB1::CTNNB1 fusion-a case report on a rare entity.

Endometrial stromal tumors are rare lesions with a diverse morphology, which may make achieving the correct diagnosis challenging in some cases. We report a case of a uterine mesenchymal tumor diagnosed as endometrial stromal nodule with a peculiar whorled morphology and GREB1::CTNNB1 fusion confirmed by transcriptome RNA sequencing. The tumor was sharply demarcated, lacked invasive growth, and had benign behavior, as the patient remained without disease recurrence 15 years later.

Variants of NAV3, a neuronal morphogenesis protein, cause intellectual disability, developmental delay, and microcephaly.

Microtubule associated proteins (MAPs) are widely expressed in the central nervous system, and have established roles in cell proliferation, myelination, neurite formation, axon specification, outgrowth, dendrite, and synapse formation. We report eleven individuals from seven families harboring predicted pathogenic biallelic, de novo, and heterozygous variants in the NAV3 gene, which encodes the microtubule positive tip protein neuron navigator 3 (NAV3). All affected individuals have intellectual disability (ID), microcephaly, skeletal deformities, ocular anomalies, and behavioral issues.

Prediction of nonresectability using the updated Predictive Index value model assessed by imaging and surgery in tubo-ovarian cancer: a prospective multicenter ISAAC study.

Background: A laparoscopy-based scoring system was developed by Fagotti et al (Fagotti or Predictive Index value (PIV)score) based on the intraoperative presence or absence of carcinomatosis on predefined sites. Later, the authors updated the PIV score calculated only in the absence of one or both absolute criteria of nonresectability (mesenteric retraction and miliary carcinomatosis of the small bowel) (updated PIV model).

Objective: The aim was to demonstrate the noninferiority of ultrasound to other imaging methods (contrast enhanced computed tomography (CT) and whole-body diffusion-weighted magnetic resonance imaging (WB-DWI)/MRI) in predicting nonresectable tumor (defined as residual disease >1 cm) using the updated PIV model in patients with tubo-ovarian cancer.

Leber hereditary optic neuropathy in Czechia and Slovakia: Quality of life and costs from patient perspective.

Introduction: Leber hereditary optic neuropathy (LHON) is the most frequent mitochondrial disease causing dyschromatopsia and progressive central visual loss that is subacute in progression and painless. Several studies have been published assessing QoL in patients with LHON, but no estimate of the economic burden has been reported to date. This study aims to quantify direct non-medical and indirect costs (productivity loss) incurred by LHON patients and their informal caregivers in Czechia and Slovakia, as well as to assess their quality of life.

Evaluation of adherence to abiraterone therapy in prostate cancer patients based on a population pharmacokinetic model.

Aims: Abiraterone treatment requires regular drug intake under fasting conditions due to pronounced food effect, which may impact patient adherence. The aim of this prospective study was to evaluate adherence to abiraterone treatment in patients with prostate cancer. To achieve this aim, an abiraterone population pharmacokinetic model was developed and patients' adherence has been estimated by comparison of measured levels of abiraterone with population model-based simulations.

Large gene deletions as a cause of muscular dystrophy and their estimated genesis.

Background: Transport protein particle (TRAPP) is a multiprotein complex that functions in localising proteins to the Golgi compartment. The TRAPPC11 subunit has been implicated in diseases affecting muscle, brain, eye and to some extent liver. We present three patients who are compound heterozygotes for a missense variant and a structural variant in the gene.

Sentinel lymph node pathological ultrastaging: Final outcome of the Sentix prospective international study in patients with early-stage cervical cancer.

Objective: To report the outcome of SLN staging in the SENTIX international prospective trial of SLN biopsy in patients with cervical cancer with an intensive ultrastaging protocol and central quality control and to evaluate how the intensity of pathological assessment correlates with metastatic detection rate in SLNs.

Methods: Eligible were patients with stages T1a1/LVSI+ to T1b2 (<4 cm, ≤2 cm for fertility sparing), common tumor types, no suspicious lymph nodes on imaging, and bilateral SLN detection. SLNs were examined intraoperatively and processed by an intensive protocol for ultrastaging (paraffin blocks sectioned completely in 150-μm intervals/levels).

Blau Syndrome: Challenging Molecular Genetic Diagnostics of Autoinflammatory Disease.

The aim of this study was to describe the clinical and molecular genetic findings in seven individuals from three unrelated families with Blau syndrome. A complex ophthalmic and general health examination including diagnostic imaging was performed. The mutational hot spot located in exon 4 was Sanger sequenced in all three probands.

Germline pathogenic variants in the MRE11, RAD50, and NBN (MRN) genes in cancer predisposition: A systematic review and meta-analysis.

The MRE11, RAD50, and NBN genes encode the MRN complex sensing DNA breaks and directing their repair. While carriers of biallelic germline pathogenic variants (gPV) develop rare chromosomal instability syndromes, the cancer risk in heterozygotes remains controversial. We performed a systematic review and meta-analysis of 53 studies in patients with different cancer diagnoses to better understand the cancer risk.

Enhancing Guided Bone Regeneration with a Novel Carp Collagen Scaffold: Principles and Applications.

Bone defects resulting from trauma, surgery, and congenital, infectious, or oncological diseases are a functional and aesthetic burden for patients. Bone regeneration is a demanding procedure, involving a spectrum of molecular processes and requiring the use of various scaffolds and substances, often yielding an unsatisfactory result. Recently, the new collagen sponge and its structural derivatives manufactured from European carp () were introduced and patented.

Analysis of striatal connectivity corresponding to striosomes and matrix in de novo Parkinson's disease and isolated REM behavior disorder.

Striosomes and matrix are two compartments that comprise the striatum, each having its own distinct immunohistochemical properties, function, and connectivity. It is currently not clear whether prodromal or early manifest Parkinson's disease (PD) is associated with any striatal matrix or striosomal abnormality. Recently, a method of striatal parcellation using probabilistic tractography has been described and validated, using the distinct connectivity of these two compartments to identify voxels with striosome- and matrix-like connectivity.

Alzheimer's disease approaches - Focusing on pathology, biomarkers and clinical trial candidates.

The strategy for the development of new drugs for Alzheimer's disease (AD) recognizes that an effective therapy requires early therapeutic intervention and a multifactorial approach that considers the individual initiators of AD development. Current knowledge of AD includes the understanding of pathophysiology, risk factors, biomarkers, and the evolving patterns of biomarker abnormalities. This knowledge is essential in identifying potential molecular targets for new drug development.

Efficacy of rehabilitation treatments in improving functioning in patients with fibromyalgia: A systematic review and meta-analysis of randomized controlled trials.

Background: Fibromyalgia is a debilitating condition marked by persistent pain and reduced functionality. Various therapeutic methods have been suggested to alleviate symptoms in individuals with fibromyalgia, yet the impact of diverse rehabilitation strategies remains unclear.

Objective: This systematic review and meta-analysis aimed at assessing the efficacy of rehabilitation interventions in improving functioning in fibromyalgia patients.

An extensive immunohistochemical analysis of 290 ovarian adult granulosa cell tumors with 29 markers.

The current knowledge about the immunohistochemical features of adult granulosa cell tumor (AGCT) is mostly limited to the "traditional" immunohistochemical markers of sex cord differentiation, such as inhibin, calretinin, FOXL2, SF1, and CD99. Knowledge about the immunohistochemical markers possibly used for predictive purpose is limited. In our study, we focused on the immunohistochemical examination of 290 cases of AGCT classified based on strict diagnostic criteria, including molecular testing.

Leg stereotypy syndrome: phenomenological and quantitative analysis.

Background: Leg stereotypy syndrome (LSS) is a very common, yet underrecognized condition. The pathophysiology of the condition is not well understood.

Objective: To evaluate and describe the visual kinematic characteristics of the repetitive leg movements in individuals with LSS.

Vancomycin population pharmacokinetics and dosing proposal for the initial treatment in obese adult patients.

Aim: The aim of this study was to develop a vancomycin population pharmacokinetic model in adult obese patients and propose covariate-based dosing individualization in order to maximize the achievement of the newly recommended PK/PD target, according to a revised consensus guideline from 2020.

Methods: Therapeutic drug monitoring data from initial vancomycin therapy (first 3 days of treatment) in adult obese (BMI ≥ 30 kg/m) patients from 2013 to 2022 were analyzed using a non-linear mixed-effects modeling method, and Monte Carlo simulations were then used to find the optimal dosage maximizing the PK/PD target attainment.

Results: A total of 147 vancomycin serum levels obtained from 138 patients were included in the analysis.

Vancomycin loading dose individualization in a population of obese patients undergoing haemodialysis based on population pharmacokinetic model.

This study aimed to develop a vancomycin population pharmacokinetic model in obese adult patients treated with intermittent haemodialysis and propose a model-based loading dose strategy ensuring attainment of newly recommended AUC-based PK/PD target. Retrospective cross-sectional analysis was performed among obese haemodialysis dependent adult patients treated with intravenous vancomycin. A pharmacokinetic population model was developed using a nonlinear mixed-effects modelling approach and Monte Carlo simulations were used to identify the optimal loading dose for PK/PD target attainment during the first 48 h of treatment.

RAD18 directs DNA double-strand break repair by homologous recombination to post-replicative chromatin.

RAD18 is an E3 ubiquitin ligase that prevents replication fork collapse by promoting DNA translesion synthesis and template switching. Besides this classical role, RAD18 has been implicated in homologous recombination; however, this function is incompletely understood. Here, we show that RAD18 is recruited to DNA lesions by monoubiquitination of histone H2A at K15 and counteracts accumulation of 53BP1.

Komrower Memorial Lecture 2023. Molecular basis of phenotype expression in homocystinuria: Where are we 30 years later?

This review summarises progress in the research of homocystinuria (HCU) in the past three decades. HCU due to cystathionine β-synthase (CBS) was discovered in 1962, and Prof. Jan Peter Kraus summarised developments in the field in the first-ever Komrower lecture in 1993.