BACKGROUND: A multicomponent meningococcal serogroups ABCWY vaccine (MenABCWY) could provide broad protection against disease-causing meningococcal strains and simplify the immunisation schedule. The aim of this trial was to confirm the effect of the licensed meningococcal serogroup B (MenB) vaccine, 4CMenB, against diverse MenB strains, and to assess the breadth of immune response against a panel of 110 MenB strains for MenABCWY containing the antigenic components of 4CMenB and licensed serogroups ACWY vaccine, MenACWY-CRM, the non-inferiority of the immune response with MenABCWY versus 4CMenB and MenACWY-CRM, safety, and MenABCWY lot-to-lot consistency. METHODS: We conducted a phase 3 randomised, controlled, observer-blinded trial of healthy adolescents and young adults (age 10-25 years) across 114 centres in Australia, Canada, Czechia, Estonia, Finland, Türkiye, and the USA. Exclusion criteria included previous vaccination with a MenB vaccine or (within the last 4 years) MenACWY vaccine. Participants were randomly allocated (5:5:3:3:3:1 ratio) via a central randomisation system using a minimisation procedure to receive 4CMenB at months 0, 2, and 6 (referred to as 4CMenB 0-2-6 hereafter); or 4CMenB at months 0 and 6 (referred to as 4CMenB 0-6 hereafter); or MenABCWY (three groups, each receiving one production lot of the MenACWY-CRM component) at months 0 and 6; or MenACWY-CRM at month 0. Demonstration in the per-protocol set of the consistency of three MenACWY-CRM component lots of the MenABCWY vaccine was a primary objective (demonstrated with two-sided 95% CIs for the ratio of human serum bactericidal antibody [hSBA] geometric mean titres against each serogroup within predefined criteria [0·5-2·0]). The primary endpoints (breadth of immune response) for the MenB component of MenABCWY and 4CMenB were measured using the endogenous complement hSBA (enc-hSBA) assay against a panel of 110 diverse MenB invasive disease strains. For each serum sample, 35 strains from the 110 MenB strain panel were randomly selected for testing. The 4CMenB breadth of immune response data have been published separately. For MenABCWY, breadth of immune response was assessed in two analyses: a test-based analysis of the percentage of samples (tests) without bactericidal serum activity against MenB strains 1 month after two MenABCWY doses versus the percentage after one MenACWY-CRM dose in the per-protocol set, and a responder-based analysis of the percentage of participants (responders) whose sera killed 70% or more strains at 1 month after two MenABCWY doses in the full analysis set. A lower limit of two-sided 95% CI above 65% would demonstrate breadth of immune response. Other primary outcomes included non-inferiority (5% margin) of two MenABCWY doses versus two 4CMenB doses by enc-hSBA assay in the per-protocol set, non-inferiority (10% margin) of two MenABCWY doses versus one MenACWY-CRM dose in MenACWY vaccine-naive participants by traditional hSBA assay in the per-protocol set, and safety in all vaccinated participants. This trial is registered with ClinicalTrials.gov, NCT04502693, and is complete. FINDINGS: Between Aug 14, 2020, and Sept 3, 2021, 3651 participants were enrolled and randomly allocated (900 in the 4CMenB 0-2-6 group and 908 in the 4CMenB 0-6 group, 1666 in the three MenABCWY groups combined, and 177 in the MenACWY-CRM group). All primary objectives for MenABCWY were met. Consistency of immune responses against the three production lots of the MenACWY component of MenABCWY was demonstrated since two-sided 95% CIs for the ratios of hSBA geometric mean titres against serogroups A, C, W, and Y for each pair of lots were within the predefined equivalence criteria. The lot data were pooled for the remainder of MenABCWY endpoints. By enc-hSBA assay, breadth of immune response against the MenB strain panel was 77·9% (95% CI 76·6 to 79·2) in the test-based analysis and 84·1% (81·4 to 86·5; 687 of 817 participants) in the responder-based analysis. Non-inferiority of MenABCWY to 4CMenB was demonstrated by enc-hSBA assay: the difference in percentage of samples with bactericidal serum activity between the MenABCWY group (82·5% [95% CI 82·1 to 83·0]; 21 222 of 25 715) and 4CMenB 0-2 group (83·1% [82·7 to 83·6]; 22 921 of 27 569) was -0·61% (-1·25 to 0·03). Non-inferiority of two-dose MenABCWY to one-dose MenACWY-CRM was demonstrated by traditional hSBA assay, with differences between the MenABCWY group and MenACWY group in percentages of participants with a four-fold rise in hSBA titres of 11·3% (5·9 to 19·0) for serogroup A, 47·2% (38·1 to 56·3) for serogroup C, 35·3% (26·9 to 44·5) for serogroup W, and 27·0% (19·4 to 35·8) for serogroup Y. MenABCWY reactogenicity was mostly of mild or moderate severity and transient, with similar frequencies of adverse events in the MenABCWY and 4CMenB groups and no safety concerns were identified. INTERPRETATION: This study demonstrates breadth of immune response against a panel of 110 MenB strains for the MenB component of the investigational MenABCWY vaccine, when administered as a 0-6 months schedule to the target population of adolescents and young adults, with predefined criteria for success met for both breadth of immune response endpoints and for non-inferiority versus 4CMenB. This investigational vaccine could provide broad meningococcal serogroup coverage in a simplified immunisation schedule, thus aiding the public health attempt in preventing invasive meningococcal disease due to five Neisseria meningitidis serogroups in adolescents and young adults. FUNDING: GSK.

• MeSH
• Child MeSH
• Adult MeSH
• Immunogenicity, Vaccine * MeSH
• Single-Blind Method MeSH
• Humans MeSH
• Meningococcal Infections * prevention & control   immunology   MeSH
• Meningococcal Vaccines * immunology   adverse effects   administration & dosage   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Neisseria meningitidis, Serogroup B immunology   MeSH
• Neisseria meningitidis immunology   MeSH
• Antibodies, Bacterial blood   MeSH
• Healthy Volunteers MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Equivalence Trial MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH

OBJECTIVES: To develop a gadolinium-free MRI-based diagnosis prediction decision tree (DPDT) for adult-type diffuse gliomas and to assess the added value of gadolinium-based contrast agent (GBCA) enhanced images. MATERIALS AND METHODS: This study included preoperative grade 2-4 adult-type diffuse gliomas (World Health Organization 2021) scanned between 2010 and 2021. The DPDT, incorporating eleven GBCA-free MRI features, was developed using 18% of the dataset based on consensus readings. Diagnosis predictions involved grade (grade 2 vs. grade 3/4) and molecular status (isocitrate dehydrogenase (IDH) and 1p/19q). GBCA-free diagnosis was predicted using DPDT, while GBCA-enhanced diagnosis included post-contrast images. The accuracy of these predictions was assessed by three raters with varying experience levels in neuroradiology using the test dataset. Agreement analyses were applied to evaluate the prediction performance/reproducibility. RESULTS: The test dataset included 303 patients (age (SD): 56.7 (14.2) years, female/male: 114/189, low-grade/high-grade: 54/249, IDH-mutant/wildtype: 82/221, 1p/19q-codeleted/intact: 34/269). Per-rater GBCA-free predictions achieved ≥ 0.85 (95%-CI: 0.80-0.88) accuracy for grade and ≥ 0.75 (95%-CI: 0.70-0.80) for molecular status, while GBCA-enhanced predictions reached ≥ 0.87 (95%-CI: 0.82-0.90) and ≥ 0.77 (95%-CI: 0.71-0.81), respectively. No accuracy difference was observed between GBCA-free and GBCA-enhanced predictions. Group inter-rater agreement was moderate for GBCA-free (0.56 (95%-CI: 0.46-0.66)) and substantial for GBCA-enhanced grade prediction (0.68 (95%-CI: 0.58-0.78), p = 0.008), while substantial for both GBCA-free (0.75 (95%-CI: 0.69-0.80) and GBCA-enhanced (0.77 (95%-CI: 0.71-0.82), p = 0.51) molecular status predictions. CONCLUSION: The proposed GBCA-free diagnosis prediction decision tree performed well, with GBCA-enhanced images adding little to the preoperative diagnostic accuracy of adult-type diffuse gliomas. KEY POINTS: Question Given health and environmental concerns, is there a gadolinium-free imaging protocol to preoperatively evaluate gliomas comparable to the gadolinium-enhanced standard practice? Findings The proposed gadolinium-free diagnosis prediction decision tree for adult-type diffuse gliomas performed well, and gadolinium-enhanced MRI demonstrated only limited improvement in diagnostic accuracy. Clinical relevance Even inexperienced raters effectively classified adult-type diffuse gliomas using the gadolinium-free diagnosis prediction decision tree, which, until further validation, can be used alongside gadolinium-enhanced images to respect standard practice, despite this study showing that gadolinium-enhanced images hardly improved diagnostic accuracy.

• MeSH
• Adult MeSH
• Gadolinium MeSH
• Glioma * diagnostic imaging   MeSH
• Contrast Media * MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Brain Neoplasms * diagnostic imaging   MeSH
• Predictive Value of Tests MeSH
• Reproducibility of Results MeSH
• Decision Trees * MeSH
• Aged MeSH
• Neoplasm Grading * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

PURPOSE: Dual velocity encoding PC-MRI can produce spurious artifacts when using high ratios of velocity encoding values (VENCs), limiting its ability to generate high-quality images across a wide range of encoding velocities. This study aims to propose and compare dual-VENC correction methods for such artifacts. THEORY AND METHODS: Two denoising approaches based on spatiotemporal regularization are proposed and compared with a state-of-the-art method based on sign correction. Accuracy is assessed using simulated data from an aorta and brain aneurysm, as well as 8 two-dimensional (2D) PC-MRI ascending aorta datasets. Two temporal resolutions (30,60) ms and noise levels (9,12) dB are considered, with noise added to the complex magnetization. The error is evaluated with respect to the noise-free measurement in the synthetic case and to the unwrapped image without additional noise in the volunteer datasets. RESULTS: In all studied cases, the proposed methods are more accurate than the Sign Correction technique. Using simulated 2D+T data from the aorta (60 ms, 9 dB), the Dual-VENC (DV) error 0.82±0.07$$ 0.82\pm 0.07 $$ is reduced to: 0.66±0.04$$ 0.66\pm 0.04 $$ (Sign Correction); 0.34±0.04$$ 0.34\pm 0.04 $$ and 0.32±0.04$$ 0.32\pm 0.04 $$ (proposed techniques). The methods are found to be significantly different (p-value <0.05$$ <0.05 $$ ). Importantly, brain aneurysm data revealed that the Sign Correction method is not suitable, as it increases error when the flow is not unidirectional. All three methods improve the accuracy of in vivo data. CONCLUSION: The newly proposed methods outperform the Sign Correction method in improving dual-VENC PC-MRI images. Among them, the approach based on temporal differences has shown the highest accuracy.

• MeSH
• Algorithms * MeSH
• Aorta * diagnostic imaging   MeSH
• Artifacts * MeSH
• Phantoms, Imaging MeSH
• Image Interpretation, Computer-Assisted methods   MeSH
• Intracranial Aneurysm diagnostic imaging   MeSH
• Humans MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Brain diagnostic imaging   MeSH
• Computer Simulation MeSH
• Image Processing, Computer-Assisted * methods   MeSH
• Signal-To-Noise Ratio * MeSH
• Reproducibility of Results MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Východisko: Odběr anamnézy pomocí validovaných dotazníků neodmyslitelně patří k urogynekologickému vyšetření a sledování. Elektronická forma vyplňování dotazníků zjednodušuje sběr a zpracování dat, ale její použití může být náročné pro starší pacientky. Proto jsme vyvinuli systém MESS (Medical Electronic Survey System), který usnadňuje vyplňování dotazníků na tabletu, s důrazem na ochranu osobních údajů a uživatelskou přívětivost. Cíl: Porovnat spokojenost pacientek a jednoduchost použití mezi systémy Google Formuláře a MESS. Metodika: V prospektivní studii jsme analyzovali 193 dotazníků spokojenosti vyplněných pomocí Google Formuláře (2013–2015) a 329 dotazníků vyplněných pomocí MESS (2019–2020) spolu s ostatními dotazníky. Data byla vyhodnocena pomocí Fisherova exaktního testu či Wilcoxonova testu dle rozložení normality s hladinou významnosti p < 0,05. Výsledky: Elektronická forma vyplňování vyhovovala více pacientkám ve skupině MESS (84,5 vs. 65,6 %; p < 0,05). Vyplňování dotazníků elektronicky bylo snadné a velmi snadné pro 89,1 % s použitím MESS vs. 68,7 % pomocí Google Formuláře (p < 0,05). Nejvýraznější rozdíl byl pozorován u žen ve věku 60–69 let, kde 92,8 % pacientek vyplnilo dotazník samostatně s MESS oproti 36,9 % u Google Formuláře. U žen mladších 60 let nebyly rozdíly statisticky významné. Závěr: Systém MESS zefektivnil práci lékařů a zpřístupnil metodu elektronického vyplňování i starším pacientkám s poruchami pánevního dna.

Background: Evaluation of the quality of life using validated measures is an essential part of urogynecology examination and follow-up. Questionnaires administered in paper form generate paper waste or high demands for storage. Score calculation for some questionnaires may be demanding and time-consuming. The electronic format of completing questionnaires simplifies data collection and processing, but may be challenging for older patients. We developed a Medical Electronic Survey System (MESS), which facilitates completion of questionnaires on a tablet PC with an emphasis on data protection and user-friendliness for the elderly. Objective: To compare patient satisfaction and ease of use between Google Forms and MESS. Methods: This was a prospective cohort study comparing the answers to a satisfaction questionnaire completed using Google Forms (193 questionnaires between 2013–2015) and MESS (329 questionnaires between 2019–2020), along with other clinically used validated questionnaires. The answers to the questionnaire were compared using a Fisher’s Exact Test or a Wilcoxon Two Sample test, with a significance level of P < 0.05. Results: The electronic form of questionnaire completion suited more women in case of MESS (84.5 vs. 65.6%; P < 0.05). Completing questionnaires electronically was rated as easy or very easy by 89.1% of patients using MESS compared to 68.7% using Google Forms; P < 0.05. The electronic form of filling-in the questionnaires was very difficult or impossible especially for women using Google Forms (31 vs. 11%; P < 0.05). The major difference in questionnaire completion without any help was observed in the age group 60–69 years. No differences were observed in women under 60 years of age. All clinicians observed significant facilitation of their work. Conclusion: MESS has made the method of electronic questionnaire completion available even to elderly patients with pelvic floor disorders. It was positively accepted even by patients who are not familiar with any electronic devices.

• Keywords
• Google formuláře, MESS,
• MeSH
• Adult MeSH
• Electronic Health Records * statistics & numerical data   MeSH
• Middle Aged MeSH
• Humans MeSH
• Pelvic Floor Disorders diagnosis   MeSH
• Prospective Studies MeSH
• Surveys and Questionnaires MeSH
• Data Collection methods   MeSH
• Aged MeSH
• Patient Satisfaction * statistics & numerical data   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Monotherapy with a potent P2Y12 receptor antagonist after 1 month of dual antiplatelet therapy (DAPT) may reduce bleeding in the absence of increased ischaemic events compared to 12-month DAPT in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). PCI guidance with optical coherence tomography (OCT) may enhance stent expansion. COMPARE STEMI ONE is an international, multicentre, open-label, randomised controlled trial. In 1,656 ST-segment elevation myocardial infarction (STEMI) patients, prasugrel monotherapy after 1 month of DAPT, as compared to standard 12-month prasugrel-based DAPT, will be tested for non-inferiority for the primary composite endpoint of net adverse clinical events - defined as all-cause death, myocardial infarction, stroke, or Bleeding Academic Research Consortium Type 3 or 5 bleeding events - at 11 months after randomisation. Furthermore, an ancillary substudy will test the superiority of OCT-guided versus angiography-guided staged complete revascularisation in achieving a larger minimal stent area (MSA) in non-culprit lesions during staged procedures. COMPARE STEMI ONE is the first randomised controlled trial assessing an abbreviated 1-month DAPT regimen followed by prasugrel monotherapy in the context of STEMI. The trial will also study the value of OCT-guided PCI in terms of the MSA of non-culprit lesions and may elucidate potential synergies between intravascular imaging-guided PCI and abbreviated DAPT regimens. (ClinicalTrials.gov: NCT05491200).

• MeSH
• Purinergic P2Y Receptor Antagonists * therapeutic use   MeSH
• ST Elevation Myocardial Infarction * therapy   drug therapy   diagnostic imaging   surgery   MeSH
• Platelet Aggregation Inhibitors * therapeutic use   MeSH
• Coronary Angiography methods   MeSH
• Percutaneous Coronary Intervention * methods   MeSH
• Humans MeSH
• Tomography, Optical Coherence * methods   MeSH
• Prasugrel Hydrochloride * therapeutic use   MeSH
• Randomized Controlled Trials as Topic MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Clinical Trial Protocol MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH

Infectious diseases, including bacterial, fungal, and viral, have once again gained urgency in the drug development pipeline after the recent COVID-19 pandemic. Tuberculosis (TB) is an old infectious disease for which eradication has not yet been successful. Novel agents are required to have potential activity against both drug-sensitive and drug-resistant strains of Mycobacterium tuberculosis (Mtb), the causative agent of TB. In this study, we present a series of 2-phenyl-N-(pyridin-2-yl)acetamides in an attempt to investigate their possible antimycobacterial activity, cytotoxicity on the HepG2 liver cancer cell line, and-as complementary testing-their antibacterial and antifungal properties against a panel of clinically important pathogens. This screening resulted in one compound with promising antimycobacterial activity-compound 12, MICMtb H37Ra = 15.625 μg/mL (56.26 μM). Compounds 17, 24, and 26 were further screened for their antiproliferative activity against human epithelial kidney cancer cell line A498, human prostate cancer cell line PC-3, and human glioblastoma cell line U-87MG, where they were found to possess interesting activity worth further exploration in the future.

• MeSH
• Acetamides * chemistry   pharmacology   MeSH
• Antifungal Agents pharmacology   chemistry   chemical synthesis   MeSH
• Antitubercular Agents pharmacology   chemistry   MeSH
• Hep G2 Cells MeSH
• Humans MeSH
• Microbial Sensitivity Tests * MeSH
• Mycobacterium tuberculosis * drug effects   MeSH
• Cell Line, Tumor MeSH
• Cell Proliferation * drug effects   MeSH
• Antineoplastic Agents pharmacology   chemistry   MeSH
• Pyridines chemistry   pharmacology   MeSH
• SARS-CoV-2 drug effects   MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

PURPOSE: To evaluate the diagnostic efficacy of serum microRNAs in predicting pathologic findings of retroperitoneal lymph node dissection (RPLND) in patients with testicular germ cell tumors (TGCT). METHODS: PUBMED, SCOPUS, and Cochrane Library were searched in August 2024 to identify eligible studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. RESULTS: Nine studies comprising 603 patients were selected in this review. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of microRNA-371a-3p for predicting viable tumor other than pure teratoma in RPLND specimen were 0.76 (95% CI 0.49-0.90), 0.97 (95% CI 0.81-0.99) and 31.75 (95% CI 9.24-109.10), respectively. The pooled sensitivity for primary and post-chemotherapy RPLND (PC-RPLND), were 0.77 (95% CI 0.47-0.93) and 0.73 (95% CI 0.28-0.95), respectively. The pooled specificity for primary and PC-RPLND were 0.92 (95% CI 0.72-0.98) and 0.99 (95% CI 0.62-1.00), respectively. The pooled DOR for primary and PC-RPLND were 13.86 (95% CI 2.97-64.79) and 64.11 (95% CI 13.09-313.98), respectively. The major limitation is the lack of standardization of miR371 testing. CONCLUSION: miR-371a-3p is a relatively sensitive and highly specific marker for predicting viable tumors in RPLND pathologic findings. The DOR was particularly significant for patients who underwent PC-RPLND. While serum microRNAs may be useful in distinguishing viable germ cell tumors from necrosis, fibrosis, and teratomas, their ability to differentiate teratomas from necrosis is limited. Well-designed prospective studies are essential to enhance our understanding of the predictive performance of microRNAs.

• MeSH
• Neoplasms, Germ Cell and Embryonal * blood   pathology   diagnosis   genetics   MeSH
• Humans MeSH
• Lymph Node Excision * MeSH
• Lymphatic Metastasis MeSH
• MicroRNAs * blood   MeSH
• Predictive Value of Tests MeSH
• Retroperitoneal Space MeSH
• Testicular Neoplasms * blood   pathology   diagnosis   genetics   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Review MeSH
• Systematic Review MeSH

BACKGROUND: This study develops a deep learning-based automated lesion segmentation model for whole-body 3D18F-fluorodeoxyglucose (FDG)-Position emission tomography (PET) with computed tomography (CT) images agnostic to disease location and site. METHOD: A publicly available lesion-annotated dataset of 1014 whole-body FDG-PET/CT images was used to train, validate, and test (70:10:20) eight configurations with 3D U-Net as the backbone architecture. The best-performing model on the test set was further evaluated on 3 different unseen cohorts consisting of osteosarcoma or neuroblastoma (OS cohort) (n = 13), pediatric solid tumors (ST cohort) (n = 14), and adult Pheochromocytoma/Paraganglioma (PHEO cohort) (n = 40). Both lesion-level and patient-level statistical analyses were conducted to validate the performance of the model on different cohorts. RESULTS: The best performing 3D full resolution nnUNet model achieved a lesion-level sensitivity and DISC of 71.70 % and 0.40 for the test set, 97.83 % and 0.73 for ST, 40.15 % and 0.36 for OS, and 78.37 % and 0.50 for the PHEO cohort. For the test set and PHEO cohort, the model has missed small volume and lower uptake lesions (p < 0.01), whereas no statistically significant differences (p > 0.05) were found in the false positive (FP) and false negative lesions volume and uptake for the OS and ST cohort. The predicted total lesion glycolysis is slightly higher than the ground truth because of FP calls, which experts can easily check and reject. CONCLUSION: The developed deep learning-based automated lesion segmentation AI model which utilizes 3D_FullRes configuration of the nnUNet framework showed promising and reliable performance for the whole-body FDG-PET/CT images.

• MeSH
• Whole Body Imaging * methods   MeSH
• Deep Learning * MeSH
• Child MeSH
• Adult MeSH
• Fluorodeoxyglucose F18 * MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Neoplasms * diagnostic imaging   MeSH
• Positron Emission Tomography Computed Tomography * methods   MeSH
• Image Processing, Computer-Assisted * methods   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Validation Study MeSH

The disease currently known as frontotemporal dementia (FTD) has undergone a complex evolution from its first description by Arnold Pick and later by Alois Alzheimer, through the first clinicopathological criteria introduced by David Neary and David Mann, to its current nomenclatural perception as a complex clinicopathological entity. Currently, Frontotemporal lobar degeneration is viewed as a heterogeneous syndrome caused by progressive degeneration of the frontal and temporal lobes of the brain. Clinically, it can manifest as three syndromes of frontotemporal dementia (behavioral variant of FTD, progressive non-fluent aphasia and semantic dementia) but also as so-called "overlap" syndromes involving corticobasal degeneration and progressive supranuclear palsy. Its prevalence is about 10 % among all dementias and 40 % among dementias with onset between 45 and 65 years of age. The clinical manifestation of the different subtypes varies, the common denominator being behavioral disturbances and impairment of fatic, gnostic and executive functions. Mnestic and visuo-spatial functions, although preserved for a relatively long time, are superimposed by personality disintegration, fatic, gnostic and executive dysfunction. Compared with Alzheimer's disease, it generally has an earlier age of onset, a more rapid course and more devastating impairment of individual cognitive domains. FTD has a heritability of more than 30 % according to current knowledge. The main genes involved are MAPT, C9orf72 and GRN. More rarely affected genes are VCP, TDP-43, FUS and CHMP2B. In our article, we focus on the genetics of FTD and the clinic-genetic-pathological correlations. We also aim to provide a plastic picture of how individual mutations affect the molecular mechanisms of neurodegeneration.

• MeSH
• Epigenesis, Genetic genetics   MeSH
• Frontotemporal Dementia * diagnosis   genetics   classification   MeSH
• Genetic Testing methods   MeSH
• Humans MeSH
• Primary Progressive Nonfluent Aphasia diagnosis   genetics   MeSH
• Progranulins genetics   MeSH
• tau Proteins genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Rare, germline loss-of-function variants in a handful of DNA repair genes are associated with epithelial ovarian cancer. The aim of this study was to evaluate the role of rare, coding, loss-of-function variants across the genome in epithelial ovarian cancer. We carried out a gene-by-gene burden test with various histotypes using data from 2573 non-mucinous cases and 13,923 controls. Twelve genes were associated at a False Discovery Rate of less than 0.1 of which seven were the known ovarian cancer susceptibility genes BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH6 and PALB2. The other five genes were OR2T35, HELB, MYO1A and GABRP which were associated with non-high-grade serous ovarian cancer and MIGA1 which was associated with high-grade serous ovarian cancer. Further support for the association of HELB association comes from the observation that loss-of-function variants in HELB are associated with age at natural menopause and Mendelian randomisation analysis shows an association between genetically predicted age at natural menopause and endometrioid ovarian cancer, but not high-grade serous ovarian cancer.

• MeSH
• Adult MeSH
• Carcinoma, Ovarian Epithelial * genetics   pathology   MeSH
• Genetic Predisposition to Disease MeSH
• Middle Aged MeSH
• Humans MeSH
• Ovarian Neoplasms * genetics   pathology   MeSH
• Exome Sequencing MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH