Can an extracorporeal glenoid aiming device be used to optimize the position of the glenoid component in total shoulder arthroplasty?

Purpose: Successful total shoulder arthroplasty (TSA) requires a correct position of the glenoid component. This study compares the accuracy of the positioning with a new developed glenoid aiming device and virtual three-dimensional computed tomography (3D-CT) scan positioning. Materials and Methods: On 39 scapulas from cadavers, a K-wire (KDev) was positioned using the glenoid aiming device. It consists of glenoid components connected to the aiming device, which cover 150 degrees of the inferior glenoid circle, has a fixed version and inclination and is available with several different radii. The aiming device is stabilized at the most medial scapular point. The K-wire is drilled from the center of the glenoid component to this most medial point. All scapulas were also scanned with CT and 3D reconstructed. A virtual K-wire (Kct) was positioned in the center of the glenoid and in the scapular plane. Several parameters were compared. Radius of the chosen glenoid component (rDev) and the virtual radius of the glenoid circle (rCT), spinal scapular length with the device (SSLdev) and virtual (SSLct), version and inclination between KDev and Kct, difference between entry point and exit point ("Matsen"-point). Results: Mean rDev: 14 mm +/- 1.7 mm and mean rCT: 13.5 mm +/- 1.6 mm. There was no significant difference between SSLdev (110.6 mm +/- 7.5 mm) and SSLct (108 mm +/- 7.5 mm). The version of KDev and Kct was -2.53 degrees and -2.17 degrees and the inclination 111.29 degrees and 111.66 degrees, respectively. The distance between the "Matsen-point" device and CT was 1.8 mm. Conclusion: This glenoid aiming device can position the K-wire on the glenoid with great accuracy and can, therefore, be helpful to position the glenoid component in TSA. The level of evidence: II

STrengthening the Reporting of OBservational studies in Epidemiology - Molecular Epidemiology (STROBE-ME): An extension of the STROBE statement

Advances in laboratory techniques have led to a rapidly increasing use of biomarkers in epidemiological studies. Biomarkers of internal dose, early biological change, susceptibility and clinical outcomes are used as proxies for investigating interactions between external and / or endogenous agents and body components or processes. The need for improved reporting of scientific research led to influential statements of recommendations such as the STrengthening Reporting of OBservational studies in Epidemiology (STROBE) statement. The STROBE initiative established in 2004 aimed to provide guidance on how to report observational research. Its guidelines provide a user-friendly checklist of 22 items to be reported in epidemiological studies, with items specific to the three main study designs: cohort studies, case-control studies and cross-sectional studies. The present STrengthening the Reporting of OBservational studies in Epidemiology - Molecular Epidemiology (STROBE-ME) initiative builds on the STROBE statement implementing nine existing items of STROBE and providing 17 additional items to the 22 items of STROBE checklist. The additions relate to the use of biomarkers in epidemiological studies, concerning collection, handling and storage of biological samples; laboratory methods, validity and reliability of biomarkers; specificities of study design; and ethical considerations. The STROBE-ME recommendations are intended to complement the STROBE recommendation

50 years existence and active participation of EEMS (now EEMGS) in the scientific community:A driver of European and international scientific collaborations for the protection of the environment and human health from genome stressors

EEMS and its successor Society EEMGS have provided a dynamic and successful platform to stimulate research and exchanges among the different actors involved in the protection of the environment and of human health from exposure to genome stressors. It includes basic, translational and applied research projects. This was possible due to the enthusiasm, creativity and support of scientists convinced of the importance of these issues. In the future young scientists will take over with new questions, new challenges, new technologies, new discoveries and new applications. A major challenge is the ethical questions emerging from the impressive potential of present genetic technologies capable of impacting the evolution of nature and humankind. The EEMGS, where academics, regulators and industries meet, should play a central role in these aspects, in particular in support of primary prevention and the establishment of internationally recognized guidelines. Collaboration with colleagues and other teams are of great importance to establish a stimulating open dialogue on scientific questions. However the key issues remain to do careful and rigorous research; to use logic and background knowledge; to define adequate experimental designs; to provide transparency in the protocols; to check repeatability of the results and to combine several statistical approaches in the quest to get to the truth. Among the many challenges ahead, re-evaluation of some key fundamental questions is necessary, such as the interplay between genetics and epigenetics, the existence of specific germ cell mutagens or the identification of the mechanisms leading to mutagen induced diseases. Translational and applied research will further include the development of systemic biomonitoring protocols, if possible in a single biological sample, the redaction of internationally harmonized guidelines but also the organization of platforms between geneticists and physicians open to all actors in the field. The creation of an independent European center to assess risk from exposure to mutagens, in particular in the light of the problematic of global warming might be very helpful.</p

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

RNAcentral : a hub of information for non-coding RNA sequences

RNAcentral is a comprehensive database of non-coding RNA (ncRNA) sequences, collating information on ncRNA sequences of all types from a broad range of organisms. We have recently added a new genome mapping pipeline that identifies genomic locations for ncRNA sequences in 296 species. We have also added several new types of functional annotations, such as tRNA secondary structures, Gene Ontology annotations, and miRNA-target interactions. A new quality control mechanism based on Rfam family assignments identifies potential contamination, incomplete sequences, and more. The RNAcentral database has become a vital component of many workflows in the RNA community, serving as both the primary source of sequence data for academic and commercial groups, as well as a source of stable accessions for the annotation of genomic and functional features. These examples are facilitated by an improved RNAcentral web interface, which features an updated genome browser, a new sequence feature viewer, and improved text search functionality. RNAcentral is freely available at https://rnacentral.org

RNAcentral 2021: secondary structure integration, improved sequence search and new member databases

RNAcentral is a comprehensive database of non-coding RNA (ncRNA) sequences that provides a single access point to 44 RNA resources and >18 million ncRNA sequences from a wide range of organisms and RNA types. RNAcentral now also includes secondary (2D) structure information for >13 million sequences, making RNAcentral the world's largest RNA 2D structure database. The 2D diagrams are displayed using R2DT, a new 2D structure visualization method that uses consistent, reproducible and recognizable layouts for related RNAs. The sequence similarity search has been updated with a faster interface featuring facets for filtering search results by RNA type, organism, source database or any keyword. This sequence search tool is available as a reusable web component, and has been integrated into several RNAcentral member databases, including Rfam, miRBase and snoDB. To allow for a more fine-grained assignment of RNA types and subtypes, all RNAcentral sequences have been annotated with Sequence Ontology terms. The RNAcentral database continues to grow and provide a central data resource for the RNA community

RNAcentral 2021: secondary structure integration, improved sequence search and new member databases.

RNAcentral is a comprehensive database of non-coding RNA (ncRNA) sequences that provides a single access point to 44 RNA resources and >18 million ncRNA sequences from a wide range of organisms and RNA types. RNAcentral now also includes secondary (2D) structure information for >13 million sequences, making RNAcentral the world's largest RNA 2D structure database. The 2D diagrams are displayed using R2DT, a new 2D structure visualization method that uses consistent, reproducible and recognizable layouts for related RNAs. The sequence similarity search has been updated with a faster interface featuring facets for filtering search results by RNA type, organism, source database or any keyword. This sequence search tool is available as a reusable web component, and has been integrated into several RNAcentral member databases, including Rfam, miRBase and snoDB. To allow for a more fine-grained assignment of RNA types and subtypes, all RNAcentral sequences have been annotated with Sequence Ontology terms. The RNAcentral database continues to grow and provide a central data resource for the RNA community. RNAcentral is freely available at https://rnacentral.org

Decision-Making for Endovascular Thrombectomy in Patients With Large Vessel Occlusions and Mild Neurological Deficit: A Consensus Statement

Acute ischemic stroke patients with mild deficits (National Institutes of Health Stroke Scale [NIHSS] of 0–5) but confirmed large vessel occlusions (LVO) present a clinical challenge for endovascular thrombectomy (EVT) decisions due to limited evidence and the absence of clear guidelines. A Delphi consensus was conducted at the 2024 5T (Teamwork, Training, Technology, Technique, Transport) Think Tank conference with 40 international stroke experts. Following a systematic literature review, three iterative Delphi rounds were employed to explore EVT decision-making in strokes due to LVO with low NIHSS. Data were collected through surveys and in-person discussions, focusing on disability evaluation, imaging markers, procedural risk, and outcome scales. Consensus was achieved on key factors influencing EVT decisions. Experts emphasized the importance of symptom-specific disability (e.g., aphasia, vision loss) over NIHSS scores alone. Early neurological deterioration (END) was perceived as main concern in this patient population. Imaging markers such as proximal occlusion, poor collaterals, and large penumbra were expected to be predictors of END. The anticipated technical difficulty and patient-specific factors, such as independence and quality of life, also guided decisions. The Potential of rtPA for Ischemic Strokes With Mild Symptoms (PRISMS) trial definition of disabling deficits and the 9-level modified Rankin Scale were favored as outcome measures for future studies. EVT decisions for acute ischemic strokes with mild deficit but proven LVO require nuanced, individualized approaches beyond NIHSS thresholds. Disability assessment, imaging-based risk evaluation, and patient-centered discussions are critical for optimizing outcomes, emphasizing the need for further research and standardized guidelines

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology