Stereotactic arrhythmia radioablation (STAR) is a novel, non-invasive, and promising treatment option for ventricular arrhythmias (VAs). It has been applied in highly selected patients mainly as bailout procedure, when (multiple) catheter ablations, together with anti-arrhythmic drugs, were unable to control the VAs. Despite the increasing clinical use, there is still limited knowledge of the acute and long-term response of normal and diseased myocardium to STAR. Acute toxicity appeared to be reasonably low, but potential late adverse effects may be underreported. Among published studies, the provided methodological information is often limited, and patient selection, target volume definition, methods for determination and transfer of target volume, and techniques for treatment planning and execution differ across studies, hampering the pooling of data and comparison across studies. In addition, STAR requires close and new collaboration between clinical electrophysiologists and radiation oncologists, which is facilitated by shared knowledge in each collaborator's area of expertise and a common language. This clinical consensus statement provides uniform definition of cardiac target volumes. It aims to provide advice in patient selection for STAR including aetiology-specific aspects and advice in optimal cardiac target volume identification based on available evidence. Safety concerns and the advice for acute and long-term monitoring including the importance of standardized reporting and follow-up are covered by this document. Areas of uncertainty are listed, which require high-quality, reliable pre-clinical and clinical evidence before the expansion of STAR beyond clinical scenarios in which proven therapies are ineffective or unavailable.

• MeSH
• Action Potentials MeSH
• Cardiology * standards   MeSH
• Tachycardia, Ventricular * physiopathology   surgery   diagnosis   MeSH
• Consensus MeSH
• Humans MeSH
• Radiosurgery * adverse effects   standards   methods   MeSH
• Risk Factors MeSH
• Patient Selection * MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Practice Guideline MeSH
• Geographicals
• Europe MeSH

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015. Since its conception, MIBiG has been regularly updated to expand data coverage and remain up to date with innovations in natural product research. Here, we describe MIBiG version 4.0, an extensive update to the data repository and the underlying data standard. In a massive community annotation effort, 267 contributors performed 8304 edits, creating 557 new entries and modifying 590 existing entries, resulting in a new total of 3059 curated entries in MIBiG. Particular attention was paid to ensuring high data quality, with automated data validation using a newly developed custom submission portal prototype, paired with a novel peer-reviewing model. MIBiG 4.0 also takes steps towards a rolling release model and a broader involvement of the scientific community. MIBiG 4.0 is accessible online at https://mibig.secondarymetabolites.org/.

• MeSH
• Molecular Sequence Annotation MeSH
• Biological Products metabolism   chemistry   MeSH
• Biosynthetic Pathways genetics   MeSH
• Databases, Genetic * MeSH
• Data Curation MeSH
• Multigene Family * MeSH
• Publication type
• Journal Article MeSH

A growing proportion of head and neck cancer (HNC), especially oropharyngeal cancer (OPC), is caused by human papillomavirus (HPV). There are several markers for HPV-driven HNC, one being HPV early antigen serology. We aimed to investigate the diagnostic accuracy of HPV serology and its performance across patient characteristics. Data from the VOYAGER consortium was used, which comprises five studies on HNC from North America and Europe. Diagnostic accuracy, that is, sensitivity, specificity, Cohen's kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16INK4a immunohistochemistry (p16), HPV in situ hybridization (ISH) and HPV PCR as reference methods. Stratified analyses were performed for variables including age, sex, smoking and alcohol use, to test the robustness of diagnostic accuracy. A risk-factor analysis based on serology was conducted, comparing HPV-driven to non-HPV-driven OPC. Overall, HPV serology had a sensitivity of 86.8% (95% CI 85.1-88.3) and specificity of 91.2% (95% CI 88.6-93.4) for HPV-driven OPC using p16 as a reference method. In stratified analyses, diagnostic accuracy remained consistent across sex and different age groups. Sensitivity was lower for heavy smokers (77.7%), OPC without lymph node involvement (74.4%) and the ARCAGE study (66.7%), while specificity decreased for cases with <10 pack-years (72.1%). The risk-factor model included study, year of diagnosis, age, sex, BMI, alcohol use, pack-years, TNM-T and TNM-N stage. HPV serology is a robust biomarker for HPV-driven OPC, and its diagnostic accuracy is independent of age and sex. Future research is suggested on the influence of smoking on HPV antibody levels.

• MeSH
• Papillomavirus Infections * MeSH
• Humans MeSH
• Human Papillomavirus Viruses MeSH
• Human papillomavirus 16 MeSH
• Head and Neck Neoplasms * diagnosis   MeSH
• Oropharyngeal Neoplasms * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

PURPOSE: Infant and young childhood medulloblastoma (iMB) is usually treated without craniospinal irradiation (CSI) to avoid neurocognitive late effects. Unfortunately, many children relapse. The purpose of this study was to assess salvage strategies and prognostic features of patients with iMB who relapse after CSI-sparing therapy. METHODS: We assembled a large international cohort of 380 patients with relapsed iMB, age younger than 6 years, and initially treated without CSI. Univariable and multivariable Cox models of postrelapse survival (PRS) were conducted for those treated with curative intent using propensity score analyses to account for confounding factors. RESULTS: The 3-year PRS, for 294 patients treated with curative intent, was 52.4% (95% CI, 46.4 to 58.3) with a median time to relapse from diagnosis of 11 months. Molecular subgrouping was available for 150 patients treated with curative intent, and 3-year PRS for sonic hedgehog (SHH), group 4, and group 3 were 60%, 84%, and 18% (P = .0187), respectively. In multivariable analysis, localized relapse (P = .0073), SHH molecular subgroup (P = .0103), CSI use after relapse (P = .0161), and age ≥ 36 months at initial diagnosis (P = .0494) were associated with improved survival. Most patients (73%) received salvage CSI, and although salvage chemotherapy was not significant in multivariable analysis, its use might be beneficial for a subset of children receiving salvage CSI < 35 Gy (P = .007). CONCLUSION: A substantial proportion of patients with relapsed iMB are salvaged after initial CSI-sparing approaches. Patients with SHH subgroup, localized relapse, older age at initial diagnosis, and those receiving salvage CSI show improved PRS. Future prospective studies should investigate optimal CSI doses and the role of salvage chemotherapy in this population.

• MeSH
• Chronic Disease MeSH
• Child MeSH
• Cohort Studies MeSH
• Infant MeSH
• Craniospinal Irradiation * adverse effects   MeSH
• Humans MeSH
• Neoplasm Recurrence, Local MeSH
• Medulloblastoma * radiotherapy   MeSH
• Cerebellar Neoplasms * radiotherapy   MeSH
• Brain Neoplasms * therapy   MeSH
• Child, Preschool MeSH
• Prospective Studies MeSH
• Hedgehog Proteins MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Child, Preschool MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Over the last decade, research interest in defining how extracellular vesicles (EVs) shape cross-species communication has grown rapidly. Parasitic helminths, worm species found in the phyla Nematoda and Platyhelminthes, are well-recognised manipulators of host immune function and physiology. Emerging evidence supports a role for helminth-derived EVs in these processes and highlights EVs as an important participant in cross-phylum communication. While the mammalian EV field is guided by a community-agreed framework for studying EVs derived from model organisms or cell systems [e.g., Minimal Information for Studies of Extracellular Vesicles (MISEV)], the helminth community requires a supplementary set of principles due to the additional challenges that accompany working with such divergent organisms. These challenges include, but are not limited to, generating sufficient quantities of EVs for descriptive or functional studies, defining pan-helminth EV markers, genetically modifying these organisms, and identifying rigorous methodologies for in vitro and in vivo studies. Here, we outline best practices for those investigating the biology of helminth-derived EVs to complement the MISEV guidelines. We summarise community-agreed standards for studying EVs derived from this broad set of non-model organisms, raise awareness of issues associated with helminth EVs and provide future perspectives for how progress in the field will be achieved.

• MeSH
• Helminths * MeSH
• Extracellular Vesicles * physiology   MeSH
• Humans MeSH
• Reproducibility of Results MeSH
• Mammals MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers and genetic markers. A total of 10 126 head and neck cancer cases and 5254 controls from five North American and European studies were included. HPV serostatus was determined by antibodies for HPV16 early oncoproteins (E6, E7) and regulatory early proteins (E1, E2, E4). The data were split into a training set (70%) for model development and a hold-out testing set (30%) for model performance evaluation, including discriminative ability and calibration. The risk models including demographic, lifestyle risk factors and polygenic risk score showed a reasonable predictive accuracy for head and neck cancer overall. A risk model that also included HPV serology showed substantially improved predictive accuracy for oropharyngeal cancer (AUC = 0.94, 95% CI = 0.92-0.95 in men and AUC = 0.92, 95% CI = 0.88-0.95 in women). The 5-year absolute risk estimates showed distinct trajectories by risk factor profiles. Based on the UK Biobank cohort, the risks of developing oropharyngeal cancer among 60 years old and HPV16 seropositive in the next 5 years ranged from 5.8% to 14.9% with an average of 8.1% for men, 1.3% to 4.4% with an average of 2.2% for women. Absolute risk was generally higher among individuals with heavy smoking, heavy drinking, HPV seropositivity and those with higher polygenic risk score. These risk models may be helpful for identifying people at high risk of developing head and neck cancer.

• MeSH
• Genetic Markers MeSH
• Papillomavirus Infections * MeSH
• Middle Aged MeSH
• Humans MeSH
• Human Papillomavirus Viruses MeSH
• Human papillomavirus 16 genetics   MeSH
• Head and Neck Neoplasms * MeSH
• Oropharyngeal Neoplasms * MeSH
• Oncogene Proteins, Viral * genetics   MeSH
• Antibodies, Viral MeSH
• Risk Factors MeSH
• Transcription Factors genetics   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH

• MeSH
• Neurology MeSH

• Conspectus
• Patologie. Klinická medicína
• Učební osnovy. Vyučovací předměty. Učebnice
• NML Fields
• neurologie
• NML Publication type
• kolektivní monografie
• učebnice vysokých škol

BACKGROUND: Although Southeast Asia is one of the most leptospirosis afflicted regions, little is known about the diversity and molecular epidemiology of the causative agents of this widespread and emerging zoonotic disease. METHODOLOGY/PRINCIPAL FINDINGS: We used whole genome sequencing to examine genetic variation in 75 Leptospira strains isolated from patients in the Lao PDR (Laos) between 2006 and 2017. Eleven serogroups from 4 Leptospira species and 43 cgMLST-defined clonal groups (CGs) were identified. The most prevalent CG was CG272 (n = 18, 26.8%), composed of L. interrogans serogroup Autumnalis isolates. This genotype was recovered throughout the 12-year period and was associated with deaths, and with a large outbreak in neighbouring Thailand. Genome analysis reveals that the CG272 strains form a highly clonal group of strains that have, for yet unknown reasons, recently spread in Laos and Thailand. Additionally, accessory genes clearly discriminate CG272 strains from the other Leptospira strains. CONCLUSIONS/SIGNIFICANCE: The present study reveals a high diversity of Leptospira genotypes in Laos, thus extending our current knowledge of the pan- and core-genomes of these life-threatening pathogens. Our results demonstrate that the CG272 strains belong to a unique clonal group, which probably evolved through clonal expansion following niche adaptation. Additional epidemiological studies are required to better evaluate the spread of this genotype in Southeast Asia. To further investigate the key factors driving the virulence and spread of these pathogens, more intense genomic surveillance is needed, combining detailed clinical and epidemiological data.

• MeSH
• Child MeSH
• Adult MeSH
• Disease Outbreaks MeSH
• Phylogeny MeSH
• Genetic Variation * MeSH
• Genome, Bacterial * MeSH
• Genotype MeSH
• Leptospira classification   genetics   isolation & purification   MeSH
• Leptospirosis epidemiology   microbiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Molecular Epidemiology MeSH
• Multilocus Sequence Typing MeSH
• Child, Preschool MeSH
• Whole Genome Sequencing MeSH
• Animals MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Laos MeSH

Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.

• MeSH
• Genome-Wide Association Study MeSH
• Gene Expression MeSH
• Genetic Predisposition to Disease MeSH
• Haplotypes MeSH
• HLA Antigens classification   genetics   immunology   MeSH
• Immunity, Humoral * MeSH
• Papillomavirus Infections genetics   immunology   pathology   virology   MeSH
• Smoking physiopathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Human papillomavirus 16 immunology   pathogenicity   MeSH
• Quantitative Trait Loci MeSH
• Meta-Analysis as Topic MeSH
• Oropharyngeal Neoplasms genetics   immunology   pathology   virology   MeSH
• Mouth Neoplasms genetics   immunology   pathology   virology   MeSH
• Oncogene Proteins, Viral genetics   immunology   MeSH
• Antibodies, Viral biosynthesis   MeSH
• Repressor Proteins genetics   immunology   MeSH
• Risk Factors MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Capsid Proteins genetics   immunology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH

• MeSH
• Magnetic Resonance Imaging methods   MeSH
• Fetal Diseases diagnostic imaging   MeSH
• Fetus MeSH
• Ultrasonography, Prenatal methods   MeSH
• Ultrasonics MeSH
• Congenital Abnormalities diagnostic imaging   MeSH
• Fetal Development MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• radiologie, nukleární medicína a zobrazovací metody
• embryologie a teratologie
• perinatologie a neonatologie
• NML Publication type
• kolektivní monografie