Discrimination and precision of Continuous Glucose Monitoring in staging children with presymptomatic type 1 diabetes.

Context: Staging and monitoring of pre-symptomatic type 1 diabetes includes the assessment for dysglycemia.

Objective: To assess the ability of Continuous Glucose Monitoring (CGM) to differentiate between islet autoantibody-negative controls and early-stage type 1 diabetes and explore whether CGM classifiers predict progression to clinical diabetes.

Research Design And Methods: Children and adolescents participating in public health screening for islet autoantibodies in Bavaria, Germany were invited to undergo CGM with Dexcom G6.

Risk Factors for Postoperative Major Morbidity, Anastomotic Leakage, Re-Surgery and Mortality in Patients with Colonic Perforation.

: This study aimed to determine the risk factors associated with postoperative major morbidity, anastomotic/suture leakage, re-surgery and mortality in patients undergoing emergency surgery for colonic perforation. : A total of 204 adult patients treated surgically for colonic perforation from 2016 to 2021 at the University Hospital Erlangen were included in a retrospective analysis. Patient demographics and pre-, intra- and postoperative parameters were obtained and evaluated among various outcome groups (in-hospital major morbidity, anastomotic/suture leakage, re-surgery and 90-day mortality).

Neutrophil-to-Lymphocyte Ratio and Prognostic Nutritional Index Are Predictors for Overall Survival after Primary Pancreatic Resection of Pancreatic Ductal Adenocarcinoma: A Single Centre Evaluation.

Purpose: Prognostic inflammation-based parameters have been reported as useful tools in various oncologic diseases. Pancreatic ductal adenocarcinoma (PDAC) is characterized by a high mortality rate, making reliable prognostic markers highly desirable. However, there is still inconsistency in the literature regarding the efficacy of the different available scores.

Infection episodes and islet autoantibodies in children at increased risk for type 1 diabetes before and during the COVID-19 pandemic.

Objectives: To determine the impact of the COVID-19 pandemic on the incidence rates of infection and islet autoimmunity in children at risk for type 1 diabetes.

Methods: 1050 children aged 4 to 7 months with an elevated genetic risk for type 1 diabetes were recruited from Germany, Poland, Sweden, Belgium and the UK. Reported infection episodes and islet autoantibody development were monitored until age 40 months from February 2018 to February 2023.

Caesarean section and risk of type 1 diabetes.

Aims/hypothesis: Delivery by Caesarean section continues to rise globally and has been associated with the risk of developing type 1 diabetes and the rate of progression from pre-symptomatic stage 1 or 2 type 1 diabetes to symptomatic stage 3 disease. The aim of this study was to examine the association between Caesarean delivery and progression to stage 3 type 1 diabetes in children with pre-symptomatic early-stage type 1 diabetes.

Methods: Caesarean section was examined in 8135 children from the TEDDY study who had an increased genetic risk for type 1 diabetes and were followed from birth for the development of islet autoantibodies and type 1 diabetes.

Vitamin D insufficiency in infants with increased risk of developing type 1 diabetes: a secondary analysis of the POInT Study.

Background: Vitamin D insufficiency (VDI) may be a factor in the development of type 1 diabetes (T1D). The aim of this study is to investigate the presence and persistence of VDI in a large cohort of infants with increased risk of developing T1D, in light of the differences in local supplementation guidelines.

Methods: In the POInT Study, a multicentre primary prevention study between February 2018 and March 2021 in Germany, Poland, Belgium, England and Sweden, including infants aged 4-7 months at high genetic risk of developing β-cell autoantibodies, vitamin D levels were analysed at each study visit from inclusion (4-7 months) until 3 years, with an interval of 2 months (first three visits) or 4-6 months (visits 4-8).

Applying molecular genetic data at different scales to support conservation assessment of European Habitats Directive listed species: A case study of Eurasian otter in Austria.

Evaluating intraspecific genetic structure and diversity is fundamental to assessing a species' conservation status, but direct incorporation of such information into legal frameworks such as the EU's Habitats Directive is surprisingly rare. How genetic structure aligns with EU member state boundaries or biogeographic regions may be very important in designing management plans or achieving legislative goals. The Eurasian fish otter experienced a sharp population decline during the 20th century but is currently re-expanding in several countries.

CRISPR Screening Identifies Mechanisms of Resistance to KRASG12C and SHP2 Inhibitor Combinations in Non-Small Cell Lung Cancer.

Unlabelled: Although KRASG12C inhibitors show clinical activity in patients with KRAS G12C mutated non-small cell lung cancer (NSCLC) and other solid tumor malignancies, response is limited by multiple mechanisms of resistance. The KRASG12C inhibitor JDQ443 shows enhanced preclinical antitumor activity combined with the SHP2 inhibitor TNO155, and the combination is currently under clinical evaluation. To identify rational combination strategies that could help overcome or prevent some types of resistance, we evaluated the duration of tumor responses to JDQ443 ± TNO155, alone or combined with the PI3Kα inhibitor alpelisib and/or the cyclin-dependent kinase 4/6 inhibitor ribociclib, in xenograft models derived from a KRASG12C-mutant NSCLC line and investigated the genetic mechanisms associated with loss of response to combined KRASG12C/SHP2 inhibition.

Evaluating mesh fixation techniques for ventral hernia repair: A systematic review and network meta-analysis of randomised control trials.

Introduction: There is uncertainty regarding the optimal mesh fixation techniques for laparoscopic ventral and incisional hernia repair.

Aim: To perform a systematic review and network meta-analysis of randomised control trials (RCTs) to investigate the advantages and disadvantages associated with absorbable tacks, non-absorbable tacks, non-absorbable sutures, non-absorbable staples, absorbable synthetic glue, absorbable sutures and non-absorbable tacks, and non-absorbable sutures and non-absorbable tacks.

Methods: A systematic review was performed as per PRISMA-NMA guidelines.

Methylglyoxal products in pre-symptomatic type 1 diabetes.

Introduction: Progression to type 1 diabetes has emerged as a complex process with metabolic alterations proposed to be a significant driver of disease. Monitoring products of altered metabolism is a promising tool for determining the risk of type 1 diabetes progression and to supplement existing predictive biomarkers. Methylglyoxal (MG) is a reactive product produced from protein, lipid, and sugar metabolism, providing a more comprehensive measure of metabolic changes compared to hyperglycemia alone.

Improved Spatiotemporal Framework for Human Activity Recognition in Smart Environment.

The rapid development of microsystems technology with the availability of various machine learning algorithms facilitates human activity recognition (HAR) and localization by low-cost and low-complexity systems in various applications related to industry 4.0, healthcare, ambient assisted living as well as tracking and navigation tasks. Previous work, which provided a spatiotemporal framework for HAR by fusing sensor data generated from an inertial measurement unit (IMU) with data obtained by an RGB photodiode for visible light sensing (VLS), already demonstrated promising results for real-time HAR and room identification.

Critical evaluation of molecular tumour board outcomes following 2 years of clinical practice in a Comprehensive Cancer Centre.

Background: Recently, molecular tumour boards (MTBs) have been integrated into the clinical routine. Since their benefit remains debated, we assessed MTB outcomes in the Comprehensive Cancer Center Ostbayern (CCCO) from 2019 to 2021.

Methods And Results: In total, 251 patients were included.

JDQ443, a Structurally Novel, Pyrazole-Based, Covalent Inhibitor of KRAS for the Treatment of Solid Tumors.

Rapid emergence of tumor resistance via RAS pathway reactivation has been reported from clinical studies of covalent KRAS inhibitors. Thus, inhibitors with broad potential for combination treatment and distinct binding modes to overcome resistance mutations may prove beneficial. JDQ443 is an investigational covalent KRAS inhibitor derived from structure-based drug design followed by extensive optimization of two dissimilar prototypes.

The emotional well-being of parents with children at genetic risk for type 1 diabetes before and during participation in the POInT-study.

Introduction: This study examined the emotional impact that parents experience when confronted with an increased genetic risk of type 1 diabetes (T1D) in their child. Population-based screening of neonates for genetic risk of chronic disease carries the risk of increased emotional burden for parents.

Methods: Information was collected using a well-being questionnaire for parents of infants identified as having an increased risk for T1D in a multinational research study.

Elevations in blood glucose before and after the appearance of islet autoantibodies in children.

The etiology of type 1 diabetes has polygenic and environmental determinants that lead to autoimmune responses against pancreatic β cells and promote β cell death. The autoimmunity is considered silent without metabolic consequences until late preclinical stages,and it remains unknown how early in the disease process the pancreatic β cell is compromised. To address this, we investigated preprandial nonfasting and postprandial blood glucose concentrations and islet autoantibody development in 1,050 children with high genetic risk of type 1 diabetes.

Progression likelihood score identifies substages of presymptomatic type 1 diabetes in childhood public health screening.

Aims/hypothesis: The aim of this study was to develop strategies that identify children from the general population who have late-stage presymptomatic type 1 diabetes and may, therefore, benefit from immune intervention.

Methods: We tested children from Bavaria, Germany, aged 1.75-10 years, enrolled in the Fr1da public health screening programme for islet autoantibodies (n=154,462).

Safety, efficacy, and cost-effectiveness of minimally invasive esophagectomies versus open esophagectomies: an umbrella review.

Traditionally, esophageal oncological resections have been performed via open approaches with well-documented levels of morbidity and mortality complicating the postoperative course. In contemporary terms, minimally invasive approaches have garnered sustained support in all areas of surgery, and there has been an exponential adaptation of this technology in upper GI surgery with the advent of laparoscopic and robotic techniques. The current literature, while growing, is inconsistent in reporting on the benefits of minimally invasive esophagectomies (MIEs) and this makes it difficult to ascertain best practice.

Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, and Selective Covalent Oral Inhibitor of KRASG12C.

Unlabelled: Covalent inhibitors of KRASG12C have shown antitumor activity against advanced/metastatic KRASG12C-mutated cancers, though resistance emerges and additional strategies are needed to improve outcomes. JDQ443 is a structurally unique covalent inhibitor of GDP-bound KRASG12C that forms novel interactions with the switch II pocket. JDQ443 potently inhibits KRASG12C-driven cellular signaling and demonstrates selective antiproliferative activity in KRASG12C-mutated cell lines, including those with G12C/H95 double mutations.

Discovery of the Clinical Candidate MAK683: An EED-Directed, Allosteric, and Selective PRC2 Inhibitor for the Treatment of Advanced Malignancies.

Polycomb Repressive Complex 2 (PRC2) plays an important role in transcriptional regulation during animal development and in cell differentiation, and alteration of PRC2 activity has been associated with cancer. On a molecular level, PRC2 catalyzes methylation of histone H3 lysine 27 (H3K27), resulting in mono-, di-, or trimethylated forms of H3K27, of which the trimethylated form H3K27me3 leads to transcriptional repression of polycomb target genes. Previously, we have shown that binding of the low-molecular-weight compound EED226 to the H3K27me3 binding pocket of the regulatory subunit EED can effectively inhibit PRC2 activity in cells and reduce tumor growth in mouse xenograft models.

Transient Inhibition of the JAK/STAT Pathway Prevents B-ALL Development in Genetically Predisposed Mice.

Unlabelled: Preventing development of childhood B-cell acute lymphoblastic leukemia (B-ALL), a disease with devastating effects, is a longstanding and unsolved challenge. Heterozygous germline alterations in the PAX5 gene can lead to B-ALL upon accumulation of secondary mutations affecting the JAK/STAT signaling pathway. Preclinical studies have shown that this malignant transformation occurs only under immune stress such as exposure to infectious pathogens.

Resection of oesophageal and oesophagogastric junction cancer liver metastases - a summary of current evidence.

Purpose: Metastatic oesophageal cancer is commonly considered as a palliative situation with a poor prognosis. However, there is increasing evidence that well-selected patients with a limited number of liver metastases (ECLM) may benefit from a multimodal approach including surgery.

Methods: A systematic review of the current literature for randomized trials, retrospective studies, and case series with patients undergoing hepatectomies for oesophageal and oesophagogastric junction cancer liver metastases was conducted up to the 31st of August 2021 using the MEDLINE (PubMed) and Cochrane Library databases.