Deletion of atypical type II restriction genes in Clostridium cellulovorans using a Cas9-based gene editing system.

The anaerobic bacterium Clostridium cellulovorans is a promising candidate for the sustainable production of biofuels and platform chemicals due to its cellulolytic properties. However, the genomic engineering of the species is hampered because of its poor genetic accessibility and the lack of genetic tools. To overcome this limitation, a protocol for triparental conjugation was established that enables the reliable transfer of vectors for markerless chromosomal modification into C.

Ocular Safety and Toxicology of Subretinal Gene Therapy With rAAV.hPDE6A in Nonhuman Primates.

Purpose: Reports of gene therapy-associated retinal atrophies and inflammation have highlighted the importance of preclinical safety assessments of adeno-associated virus (AAV) vector systems. We evaluated in nonhuman primates (NHPs) the ocular safety and toxicology of a novel AAV gene therapy targeting retinitis pigmentosa caused by mutations in PDE6A, which has since been used in a phase I/II clinical trial (NCT04611503).

Methods: A total of 34 healthy cynomolgus animals (Macaca fascicularis) were treated with subretinal injections of rAAV.

Minimally invasive compared to open surgery in patients with low-risk cervical cancer following simple hysterectomy: An exploratory analysis from the Gynegologic Cancer Intergroup/Canadian Cancer Trials Group CX.5/SHAPE trial.

Objective: The Laparoscopic Approach to Cervical Cancer trial demonstrated that minimally invasive radical hysterectomy was associated with worse disease-free survival and overall survival among women with early-stage cervical cancer. It is unknown whether this applies to patients with low-risk disease following simple hysterectomy.

Methods: Among patients who underwent simple hysterectomy in the Simple Hysterectomy And PElvic node assessment trial, univariate and multivariate Cox models were used to assess the association of minimally invasive versus open surgery with clinical outcomes, including pelvic and extra-pelvic recurrence-free survival, overall recurrence-free survival, and overall survival.

Frontopolar Cortex Interacts With Dorsolateral Prefrontal Cortex to Causally Guide Metacognition.

Accurate metacognitive judgments about an individual's performance in a mental task require the brain to have access to representations of the quality and difficulty of first-order cognitive processes. However, little is known about how accurate metacognitive judgments are implemented in the brain. Here, we combine brain stimulation with functional neuroimaging to determine the neural and psychological mechanisms underlying the frontopolar cortex's (FPC) role in metacognition.

Incidence and treatment of anastomotic leakage after esophagectomy in German acute care hospitals: a retrospective cohort study.

Background: Anastomotic leakage (AL) is a major concern following esophagectomy due to the associated morbidity and mortality. The impact of hospital volume on postoperative outcomes after esophagectomy has previously been reported. The aim of this study was to analyze the current trends in postoperative anastomotic leakage and associated failure-to-rescue after esophagectomy in relation to hospital volume in German acute care hospitals using real-world data from the German Diagnosis-Related Groups (G-DRG) database.

Bots in white coats: are large language models the future of patient education? a multi-center cross-sectional analysis.

Objectives: Every year, around 300 million surgeries are conducted worldwide, with an estimated 4.2 million deaths occurring within 30 days after surgery. Adequate patient education is crucial, but often falls short due to the stress patients experience before surgery.

Clearing the path for whole-mount labeling and quantification of neuron- and vessel-density in adipose tissue.

White adipose tissue (WAT) comprises a plethora of cell types beyond adipocytes forming a regulatory network that ensures systemic energy homeostasis. Intertissue communication is facilitated by metabolites and signaling molecules that are spread by vasculature and nerves. Previous works indicated that WAT responds to environmental cues by adapting the abundance of these "communication routes", however, high intra-tissue heterogeneity questions the informative value of bulk or single cell analyses and underscores the necessity of whole-mount imaging.

Reimbursement policies of Swiss health insurances for the surgical treatment of symptomatic breast hypertrophy: a retrospective cohort study.

Background: Patients with symptomatic breast hypertrophy typically suffer from chronic back pain, recurrent skin irritation at the inframammary fold and/or low self-esteem resulting in impaired quality of life. Reduction mammaplasty has been shown to effectively treat symptomatic breast hypertrophy with high patient satisfaction. Despite the obvious benefits, reimbursement requests for reduction mammaplasty are initially often refused by the patient's health insurance company, thereby frequently resulting in additional examinations and eventually extra expenses.

Comparison of dark-field chest radiography and CT for the assessment of COVID-19 pneumonia.

Background: Dark-field chest radiography allows the assessment of the structural integrity of the alveoli by exploiting the wave properties of x-rays.

Purpose: To compare the qualitative and quantitative features of dark-field chest radiography in patients with COVID-19 pneumonia with conventional CT imaging.

Materials And Methods: In this prospective study conducted from May 2020 to December 2020, patients aged at least 18 years who underwent chest CT for clinically suspected COVID-19 infection were screened for participation.

Epidemiological, economic and humanistic burden of cervical intraepithelial neoplasia in Europe: A systematic literature review.

Introduction: High-grade cervical intraepithelial neoplasia (CIN) is a premalignant lesion of the cervix caused by persistent human papillomavirus (HPV) infection, which can lead to cervical cancer. Despite ongoing primary prevention efforts, considerable burden of illness remains. This study assessed the epidemiological, economic, and humanistic burden associated with high-grade CIN among adult women in Europe.

Active control over exploration improves memory in toddlers.

Across two experiments, we implemented a novel gaze-contingent eye-tracking paradigm to investigate the early emergence of memory benefits from active control over exploration and to examine how exploratory behaviours affect memory formation in early development. Toddlers (experiment 1: = 36, 18-36 months; experiment 2: = 41, 23-36 months) were either allowed to actively control their exploration (active condition) or presented with the same information that they could only passively observe (passive condition in experiment 1; yoked condition in experiment 2). They were then tested in a preferential-looking paradigm in which familiar versus novel stimuli were presented in pairs.

Factors influencing role preferences in decision-making of healthy women with BRCA1/2 pathogenic variants: subanalysis from a randomised controlled decision coaching trial.

Background: Patients who actively engage in their medical decision-making processes can experience better health outcomes. This exploratory study aimed to identify predictors of preferred and actual roles in decision-making in healthy women with BRCA1/2 pathogenic variants (PVs).

Methods: Women with BRCA1/2 PVs without a history of breast and/or ovarian cancer were recruited in six centres across Germany.

Dental and oral health assessments in the German National Cohort (NAKO).

Background: Despite considerable improvements in oral health in recent decades, caries and periodontitis are still widespread, ranking among the most prevalent diseases worldwide and requiring future research. The German National Cohort (NAKO Gesundheitsstudie, NAKO) is a large-scaled, multidisciplinary, nationwide, multi-centre, population-based, prospective cohort study with oral examinations that aims to provide a resource to study risk factors for major diseases. The aim of the present article is to provide the methodological background, to report on the data quality, and to present initial results of the oral examinations.

Lipid-Lowering Efficiency and Safety of Alirocumab 300 mg Using a 2-mL Autoinjector Device in Real-World Practice: The MARS Study.

Background: Alirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin kexin type 9 used for the reduction of low-density lipoprotein cholesterol (LDL-C) in high-risk patients not reaching their LDL-C target. Recently, a 2-mL prefilled autoinjector has been developed to support the monthly 300-mg dosing regimen with a single-injection administration.

Methods And Objectives: Monthly application of 300 mg AlirRocumab (Praluent) using the 2-mL SYDNEY Device (MARS) is a non-interventional, open, prospective, multi-center cohort study conducted in Germany between 2021 and 2023 with an observational period of 12 weeks.

Multi-tasking costs in triple-task performance despite dual-task preparation.

This study explores multi-tasking by examining the effects of transitioning from dual-task to triple-task scenarios. Our research extends beyond conventional dual-task paradigms to investigate the impact of triple-task performance on two participant groups: those unprepared in single, dual, or triple tasks (N = 14) and those previously prepared in single and dual tasks (N = 13). The study consisted of a preparation phase with nine sessions and an assessment phase with eight sessions.

Bias-corrected serum creatinine from UK Biobank electronic medical records generates an important data resource for kidney function trajectories.

Loss of kidney function is a substantial personal and public health burden. Kidney function is typically assessed as estimated glomerular filtration rate (eGFR) based on serum creatinine. UK Biobank provides serum creatinine measurements from study center assessments (SC, n = 425,147 baseline, n = 15,314 with follow-up) and emerging electronic Medical Records (eMR, "GP-clinical") present a promising resource to augment this data longitudinally.

VAE-Surv: A novel approach for genetic-based clustering and prognosis prediction in myelodysplastic syndromes.

Background And Objectives: Several computational pipelines for biomedical data have been proposed to stratify patients and to predict their prognosis through survival analysis. However, these analyses are usually performed independently, without integrating the information derived from each of them. Clustering of survival data is an underexplored problem, and current approaches are limited for biomedical applications, whose data are usually heterogeneous and multimodal, with poor scalability for high-dimensionality.

Rational choices elicit stronger sense of agency in brain and behavior.

The sense of agency is the subjective feeling of control over one's own actions and the associated outcomes. Here, we asked whether and to what extent the reasons behind our choices (operationalized by value differences, expected utility, and counterfactual option sets) drive our sense of agency. We simultaneously tested these three dimensions during a novel value-based decision-making task while recording explicit (self-reported) and implicit (brain signals) measures of agency.

The Social Construction of Categorical Data: Mixed Methods Approach to Assessing Data Features in Publicly Available Datasets.

Background: In data-sparse areas such as health care, computer scientists aim to leverage as much available information as possible to increase the accuracy of their machine learning models' outputs. As a standard, categorical data, such as patients' gender, socioeconomic status, or skin color, are used to train models in fusion with other data types, such as medical images and text-based medical information. However, the effects of including categorical data features for model training in such data-scarce areas are underexamined, particularly regarding models intended to serve individuals equitably in a diverse population.

The Use of Acellular Dermal Matrix May Not Increase 30-Day Complications in Direct-to-Implant Breast Reconstruction: A Multi-institutional Analysis of 10,177 Cases.

Background: Direct-to-implant (DTI) breast reconstruction offers immediate aesthetic and psychological benefits, but the role of acellular dermal matrix (ADM) remains debated. Using a multi-institutional database, this study evaluates and compares outcomes between ADM-assisted and non-ADM DTI procedures.

Methods: The American College of Surgeons National Surgical Quality Improvement Program database from 2008 to 2022 was queried to identify female patients who underwent DTI breast reconstruction for oncological purposes.