Directed Evolution of AAV9 for Efficient Gene Expression in Cardiomyocytes and .

Adeno-associated viral (AAV) vectors are increasingly used for preclinical and clinical cardiac gene therapy approaches. However, gene transfer to cardiomyocytes poses a challenge due to differences between AAV serotypes in terms of expression efficiency and . For example, AAV9 vectors work well in rodent heart muscle cells but not in cultivated neonatal rat ventricular cardiomyocytes (NRVCMs), necessitating the use of AAV6 vectors for studies.

Mechanistic insights into HPV-positivity in non-smokers and HPV-negativity in smokers with head and neck cancer.

Introduction: Several aspects of the involvement of HPV in the pathogenesis of HPV-associated diseases remain poorly understood including mechanistic aspects of infection and the question of why the majority of HPV-positive HNSCC-patients are non-smokers, whereas HPV-negatives are smokers. Our previous research, based on 1,100 patient samples, hypothesized an explanation for this phenomenon: Smoking induces upregulation of a mucosal protective protein (SLPI), which competes with HPV for binding to Annexin A2 (AnxA2), pivotal for HPV cell entry. Here we investigate the mechanistic aspects of our hypothesis using transfection assays.

Effects of mosquito-proofing storm drains on adult and larvae mosquito abundance: Protocol of the IDAlErt storm drAin randomiSed controlled trial (IDEAS).

and mosquitoes, known for spreading arboviruses like dengue and West Nile, thrive in cities, posing health risks to urban populations. Climate change can create suitable climatic conditions for these vectors to spread further in Europe. Cities contain numerous landscape and infrastructure elements, such as storm drains, that allow stagnant water build-up facilitating mosquito breeding.

Somatic mutations and DNA methylation identify a subgroup of poor prognosis within lower-risk myelodysplastic syndromes.

Lower risk (LR) myelodysplastic syndromes (MDS) are heterogeneous hematopoietic stem and progenitor disorders caused by the accumulation of somatic mutations in various genes including epigenetic regulators that may produce convergent DNA methylation patterns driving specific gene expression profiles. The integration of genomic, epigenomic, and transcriptomic profiling has the potential to spotlight distinct LR-MDS categories on the basis of pathophysiological mechanisms. We performed a comprehensive study of somatic mutations and DNA methylation in a large and clinically well-annotated cohort of treatment-naive patients with LR-MDS at diagnosis from the EUMDS registry (ClinicalTrials.

Predicting hydrogen atom transfer energy barriers using Gaussian process regression.

Predicting reaction barriers for arbitrary configurations based on only a limited set of density functional theory (DFT) calculations would render the design of catalysts or the simulation of reactions within complex materials highly efficient. We here propose Gaussian process regression (GPR) as a method of choice if DFT calculations are limited to hundreds or thousands of barrier calculations. For the case of hydrogen atom transfer in proteins, an important reaction in chemistry and biology, we obtain a mean absolute error of 3.

Colorectal carcinogenesis in the Lynch syndromes and familial adenomatous polyposis: trigger events and downstream consequences.

Carcinogenesis encompasses processes that lead to increased mutation rates, enhanced cellular division (tumour growth), and invasive growth. Colorectal cancer (CRC) carcinogenesis in carriers of pathogenic APC (path_APC) and pathogenic mismatch repair gene (path_MMR) variants is initiated by a second hit affecting the corresponding wild-type allele. In path_APC carriers, second hits result in the development of multiple adenomas, with CRC typically emerging after an additional 20 years.

Selective arm-usage of pre-miR-1307 dysregulates angiogenesis and affects breast cancer aggressiveness.

Background: Breast cancer is the leading cause of cancer-related mortality in women. Deregulation of miRNAs is frequently observed in breast cancer and affects tumor biology. A pre-miRNA, such as pre-miR-1307, gives rise to several mature miRNA molecules with distinct functions.

Lifestyle scores and their potential to estimate the risk of multiple non-communicable disease-related endpoints: a systematic review.

Background: Lifestyle scores have emerged as a practical tool to assess the risk of major non-communicable diseases (NCDs). However, most of them are primarily developed for single NCDs. Given the common risk factors for some of the major NCDs, we conducted a systematic review to evaluate the potential of existing lifestyle scores in predicting the risk of multiple NCD-related endpoints.

Ramadan during pregnancy and the role of dietary intake for neonatal health in Kaduna, Northwestern Nigeria: a cross-sectional study.

Background: Ramadan during pregnancy is associated with adverse offspring health outcomes. Recent evidence from Europe indicates that maternal diet during non-fasting hours might alleviate these effects. This study describes fasting, diet, and sleep habits among pregnant Muslims in Kaduna, Nigeria, and assesses impacts on neonatal health in this setting.

Advanced Automated Model for Robust Bone Marrow Segmentation in Whole-body MRI.

Rationale And Objectives: To establish an advanced automated bone marrow (BM) segmentation model on whole-body (WB-)MRI in monoclonal plasma cell disorders (MPCD), and to demonstrate its robust performance on multicenter datasets with severe myeloma-related pathologies.

Materials And Methods: The study cohort comprised multi-vendor, multi-protocol imaging data acquired with varying field strength across 8 different centers. In total, 210 WB-MRIs of 207 MPCD patients were included.

Gender-Equity Model for Liver Allocation using Artificial Intelligence (GEMA-AI) for waiting list liver transplant prioritization.

Background & Aims: We aimed to develop and validate an artificial intelligence score (GEMA-AI) to predict liver transplant (LT) waiting list outcomes using the same input variables contained in existing models.

Methods: Cohort study including adult LT candidates enlisted in the United Kingdom (2010-2020) for model training and internal validation, and in Australia (1998-2020) for external validation. GEMA-AI combined international normalized ratio, bilirubin, sodium, and the Royal Free Glomerular Filtration Rate in an explainable Artificial Neural Network.

Survival Among Patients Treated with Total Mesorectal Excision or Selective Watch-and-Wait After Total Neoadjuvant Therapy: A Pooled Analysis of the CAO/ARO/AIO-12 and OPRA Randomized Phase II Trials.

Background: Prospective data comparing watch-and-wait (WW) to mandatory total mesorectal excision (TME) in patients with locally advanced rectal cancer (LARC) remains limited, as randomized control trials assessing these two treatment approaches are considered impractical. This pooled analysis of the CAO/ARO/AIO-12 and OPRA trials analyzes survival outcomes among LARC patients managed with either a selective WW or mandatory TME strategy following total neoadjuvant therapy (TNT).

Patients And Methods: The CAO/ARO/AIO-12 and OPRA trials were multicenter, phase II trials that randomized patients with stage II/III rectal cancer to receive either induction or consolidation chemotherapy as part of TNT.

Nickel-Catalyzed Three-Component Carboamination/Cyclization of Alkynes To Access 2,3-Disubstituted Quinolines.

Presented herein is a nickel-catalyzed chemo- and regioselective three-component tandem carboamination and cyclization of terminal alkynes with organoboronic acids and anthranils for facile and modular access to 2,3-substituted quinolines. In this process, anthranil has dual roles: serving as an electrophilic aminating reagent and a redox buffer to suppress the generation of an off-cycle Ni(0) complex. Moreover, the anionic acetylacetonate (acac) ligand was found to be vital to ensure a productive Ni(I)-Ni(III)-Ni(I) catalytic cycle.

Cardiac Radiomics Analyses in Times of Photon-counting Computed Tomography for Personalized Risk Stratification in the Present and in the Future.

The need for effective early detection and optimal therapy monitoring of cardiovascular diseases as the leading cause of death has led to an adaptation of the guidelines with a focus on cardiac computed tomography (CCTA) in patients with a low to intermediate risk of coronary heart disease (CHD). In particular, the introduction of photon-counting computed tomography (PCCT) in CT diagnostics promises significant advances through higher temporal and spatial resolution, and also enables advanced texture analysis, known as radiomics analysis. Originally developed in oncological imaging, radiomics analysis is increasingly being used in cardiac imaging and research.

Persistent symptoms and clinical findings in adults with post-acute sequelae of COVID-19/post-COVID-19 syndrome in the second year after acute infection: A population-based, nested case-control study.

Background: Self-reported health problems following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are common and often include relatively non-specific complaints such as fatigue, exertional dyspnoea, concentration or memory disturbance and sleep problems. The long-term prognosis of such post-acute sequelae of COVID-19/post-COVID-19 syndrome (PCS) is unknown, and data finding and correlating organ dysfunction and pathology with self-reported symptoms in patients with non-recovery from PCS is scarce. We wanted to describe clinical characteristics and diagnostic findings among patients with PCS persisting for >1 year and assessed risk factors for PCS persistence versus improvement.

Adjuvant Chemotherapy After Resection of Localized Pancreatic Adenocarcinoma Following Preoperative FOLFIRINOX.

Importance: The effect of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX (combination leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin in full or modified dosing) chemotherapy on overall survival (OS) is unclear because current studies do not account for the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen.

Objective: To investigate the association of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX with OS, taking into account the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen.

Design, Setting, And Participants: This retrospective cohort study included patients with localized pancreatic adenocarcinoma treated with 2 to 11 cycles of preoperative (m)FOLFIRINOX followed by resection across 48 centers in 20 countries from 2010 to 2018.

Systematic review of the needs and health-related quality of life domains relevant to people surviving cancer in Europe.

Purpose: To systematically review qualitative studies on outcomes, needs, experiences, preferences, concerns and health-related quality of life (HRQoL) of people surviving cancer in Europe in the last decade.

Methods: Protocol registered ( https://www.crd.

Improving postsurgical paresis in brain tumor patients by transcranial magnetic stimulation.

Background And Objectives: Recently, reduction of transcallosal inhibition by contralateral navigated repetitive transcranial magnetic stimulation (nrTMS) improved neurorehabilitation of glioma patients with new postoperative paresis. This multicentric study examines the effect of postoperative nrTMS in brain tumor patients to treat surgery-related upper extremity paresis.

Methods: This is a secondary analysis of two randomized and three one-arm studies in brain tumor patients with new/progressive postoperative paresis.

Microvascular reconstruction in oral and maxillofacial surgery: a Europe-wide data collection.

Purpose: This study aims to analyze microvascular reconstruction in Oral and Maxillofacial Surgery (OMFS) in Europe.

Methods: Based on previous studies, a dynamic online questionnaire was developed and subjected to internal and external evaluation. The questionnaire comprised multiple-choice, rating, and open-ended questions, addressing general and specific aspects and the impacts of the COVID-19 pandemic on microvascular reconstruction in OMFS in Europe.

Survey of legislative frameworks and national recommendations governing paediatric maintenance haemodialysis in Europe.

Background: The application of international recommendations for paediatric maintenance haemodialysis (HD) could be strengthened by national laws or written recommendations. Our aim was therefore to describe the national rules governing paediatric maintenance HD in European countries.

Methods: A national representative, approved by the president of each paediatric nephrology society, was contacted in all 42 European countries to complete two online questionnaires.

ACTB::ZMIZ2-rearranged adnexal carcinoma: a second case.

A case of cutaneous adnexal neoplasm with unusual squamoid morphology and harboring an in frame ACTB::ZMIZ2 fusion transcript was recently described. Herein, we report a second case of adnexal carcinoma harboring similar morphology and an identical in frame ACTB::ZMIZ2 fusion transcript. This 2.

A proteogenomic analysis of the adiposity colorectal cancer relationship identifies GREM1 as a probable mediator.

Background: Adiposity is an established risk factor for colorectal cancer (CRC). The pathways underlying this relationship, and specifically the role of circulating proteins, are unclear.

Methods: Utilizing two-sample univariable Mendelian randomization (UVMR), multivariable Mendelian randomization (MVMR), and colocalization, based on summary data from large sex-combined and sex-specific genetic studies, we estimated the univariable associations between: (i) body mass index (BMI) and waist-hip ratio (WHR) and overall and site-specific (colon, proximal colon, distal colon, and rectal) CRC risk, (ii) BMI and WHR and circulating proteins, and (iii) adiposity-associated circulating proteins and CRC risk.

Heidelberg Adult and Pediatric Airway Registry (HAPA-Registry).

Background: Advanced airway management is of fundamental importance in almost all areas of anesthesiology, emergency medicine, and critical care. Securing the airway is of the utmost importance, as this is a prerequisite for the oxygenation of the human organism. The clinical relevance of airway management is particularly evident in the fact that the primary cause of significant anesthesia-related complications can be attributed to this field.

Anonymize or synthesize? Privacy-preserving methods for heart failure score analytics.

Aims: Data availability remains a critical challenge in modern, data-driven medical research. Due to the sensitive nature of patient health records, they are rightfully subject to stringent privacy protection measures. One way to overcome these restrictions is to preserve patient privacy by using anonymization and synthetization strategies.

City classification and health burden: Evidence from U5 malaria in the rapidly growing city of Akure, Nigeria.

Objectives: Little is known about the complex interplay between urban structure and health in rapidly urbanizing cities in Nigeria.

Methods: The study broadly used very high-resolution satellite imagery and gathered primary data. With the aid of the very high-resolution imagery and identified neighborhoods, two neighborhoods each were sampled based on their classified urban structure characteristics.