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.

Digital-Tier Strategy Improves Newborn Screening for Glutaric Aciduria Type 1.

Glutaric aciduria type 1 (GA1) is a rare inherited metabolic disease increasingly included in newborn screening (NBS) programs worldwide. Because of the broad biochemical spectrum of individuals with GA1 and the lack of reliable second-tier strategies, NBS for GA1 is still confronted with a high rate of false positives. In this study, we aim to increase the specificity of NBS for GA1 and, hence, to reduce the rate of false positives through machine learning methods.

Automated CRISPR/Cas9-based genome editing of human pluripotent stem cells using the StemCellFactory.

CRISPR/Cas9 genome editing is a rapidly advancing technology that has the potential to accelerate research and development in a variety of fields. However, manual genome editing processes suffer from limitations in scalability, efficiency, and standardization. The implementation of automated systems for genome editing addresses these challenges, allowing researchers to cover the increasing need and perform large-scale studies for disease modeling, drug development, and personalized medicine.

Closed Reduction Followed by Percutaneous Fixation of Acute Femoral Neck Fractures in Young Adults: A Retrospective Cohort Study.

Objectives: To evaluate the surgical outcomes of femoral neck fractures (FNF) in young adults treated with a closed reduction technique because it pertains to reduction quality, rates of union, and risk factors for complication.

Design: Retrospective cohort study with radiograph and electronic medical record review.

Setting: Level 1 Swiss Trauma Center.

Impact of a single blood donation on hemoglobin mass, iron stores, and maximum oxygen uptake in pre-menopausal women-A pilot study.

Background: During whole blood donation (BD), 500 mL of blood is drawn. The time interval between two BDs is at least 8-12 weeks. This period might be insufficient for restoring hemoglobin mass (Hbmass) and iron especially in women, who generally have lower Hbmass and iron availability.

Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated "Big Bang" pathway to CRC in three of the four Lynch syndromes.

Background: Colorectal cancers (CRCs) in the Lynch syndromes have been assumed to emerge through an accelerated adenoma-carcinoma pathway. In this model adenomas with deficient mismatch repair have an increased probability of acquiring additional cancer driver mutation(s) resulting in more rapid progression to malignancy. If this model was accurate, the success of colonoscopy in preventing CRC would be a function of the intervals between colonoscopies and mean sojourn time of detectable adenomas.

Impact of Burnout on Anaesthesiologists.

Professional burnout syndrome (PBS) is an issue affecting individuals and organizations alike, characterized by emotional exhaustion and reduced effectiveness resulting from overwhelming work demands. Root causes include excessive workload, unrealistic expectations, and blurred work-life boundaries, which are often intensified by organizational culture and inadequate support systems. The consequences range from decreased productivity and creativity to high turnover rates and financial strain on organizations.

Effects of Different Types of Intermittent Fasting Interventions on Metabolic Health in Healthy Individuals (EDIF): A Randomised Trial with a Controlled-Run in Phase.

The effects of intermittent fasting (IF) on health promotion in the healthy population remain controversial. Therefore, our study aimed to analyse the efficacy and feasibility of different IF protocols and evaluated the effects within a cohort with a controlled-run in phase on the body mass index (BMI) as the primary outcome, the body composition, and metabolic and haematological markers in healthy participants. A total of 25 individuals were randomised into three fasting groups: 16/8 fasting ( = 11), 20/4 fasting ( = 6), and alternate-day fasting (ADF, = 8).

A life-course approach to tackling noncommunicable diseases in women.

Women's health has been critically underserved by a failure to look beyond women's sexual and reproductive systems to adequately consider their broader health needs. In almost every country in the world, noncommunicable diseases are the leading causes of death for women. Among these, cardiovascular disease (including heart disease and stroke) and cancer are the major causes of mortality.

(Hybrid) Closed-Loop Systems: From Announced to Unannounced Exercise.

Physical activity and exercise have many beneficial effects on general and type 1 diabetes (T1D) specific health and are recommended for individuals with T1D. Despite these health benefits, many people with T1D still avoid exercise since glycemic management during physical activity poses substantial glycemic and psychological challenges - which hold particularly true for unannounced exercise when using an AID system. Automated insulin delivery (AID) systems have demonstrated their efficacy in improving overall glycemia and in managing announced exercise in numerous studies.

Evaluation of a novel CBCT conversion method implemented in a treatment planning system.

Background: To evaluate a novel CBCT conversion algorithm for dose calculation implemented in a research version of a treatment planning system (TPS).

Methods: The algorithm was implemented in a research version of RayStation (v. 11B-DTK, RaySearch, Stockholm, Sweden).

Establishing the Link between X-Chromosome Aberrations and Status, with Breast Cancer Patient Outcomes.

Ubiquitous to normal female human somatic cells, X-chromosome inactivation (XCI) tightly regulates the transcriptional silencing of a single X chromosome from each pair. Some genes escape XCI, including crucial tumour suppressors. Cancer susceptibility can be influenced by the variability in the genes that escape XCI.

Efficacy of Fasting in Type 1 and Type 2 Diabetes Mellitus: A Narrative Review.

Over the last decade, studies suggested that dietary behavior modification, including fasting, can improve metabolic and cardiovascular markers as well as body composition. Given the increasing prevalence of people with type 1 (T1DM) and type 2 diabetes mellitus (T2DM) and the increasing obesity (also in combination with diabetes), nutritional therapies are gaining importance, besides pharmaceutical interventions. Fasting has demonstrated beneficial effects for both healthy individuals and those with metabolic diseases, leading to increased research interest in its impact on glycemia and associated short- and long-term complications.

Structural evidence for intermediates during O formation in photosystem II.

In natural photosynthesis, the light-driven splitting of water into electrons, protons and molecular oxygen forms the first step of the solar-to-chemical energy conversion process. The reaction takes place in photosystem II, where the MnCaO cluster first stores four oxidizing equivalents, the S to S intermediate states in the Kok cycle, sequentially generated by photochemical charge separations in the reaction center and then catalyzes the O-O bond formation chemistry. Here, we report room temperature snapshots by serial femtosecond X-ray crystallography to provide structural insights into the final reaction step of Kok's photosynthetic water oxidation cycle, the S→[S]→S transition where O is formed and Kok's water oxidation clock is reset.

The Chromatin Regulator Mll1 Supports T Follicular Helper Cell Differentiation by Controlling Expression of Bcl6, LEF-1, and TCF-1.

T follicular helper (TFH) cells are essential for developing protective Ab responses following vaccination. Greater understanding of the genetic program leading to TFH differentiation is needed. Chromatin modifications are central in the control of gene expression.

Clavicular hook plate versus dog-bone technique for acute high-grade acromioclavicular joint dislocation: a retrospective cohort study comparing clinical outcome scores, complications, and costs.

Introduction: Arthroscopically assisted coracoclavicular (CC) ligament fixation techniques have been promoted as providing superior outcomes for the treatment of acute high-grade acromioclavicular joint (ACJ) dislocations. Nevertheless, there is a lack of high-level evidence for clinically relevant benefits. At our institute, orthopaedic surgeons use an arthroscopically assisted coracoclavicular ligament fixation technique (DB), while general trauma surgeons use a clavicular hook plate (cHP) technique.

Effects of Different Fasting Interventions on Cardiac Autonomic Modulation in Healthy Individuals: A Secondary Outcome Analysis of the EDIF Trial.

The impact of a fasting intervention on electrocardiographic (ECG) time intervals and heart rate variability (HRV) is a focus that is scarcely analyzed. The main focus of these secondary outcome data was to describe the impact of a different fasting intervention on ECG and HRV analyses. Twenty-seven healthy individuals participated in this study (11 females, aged 26.

Machine Learning Methods Improve Specificity in Newborn Screening for Isovaleric Aciduria.

Isovaleric aciduria (IVA) is a rare disorder of leucine metabolism and part of newborn screening (NBS) programs worldwide. However, NBS for IVA is hampered by, first, the increased birth prevalence due to the identification of individuals with an attenuated disease variant (so-called "mild" IVA) and, second, an increasing number of false positive screening results due to the use of pivmecillinam contained in the medication. Recently, machine learning (ML) methods have been analyzed, analogous to new biomarkers or second-tier methods, in the context of NBS.