Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response.

The DNA-damaging agent Gemcitabine (GEM) is a first-line treatment for pancreatic cancer, but chemoresistance is frequently observed. Several clinical trials investigate the efficacy of GEM in combination with targeted drugs, including kinase inhibitors, but the experimental evidence for such rationale is often unclear. Here, we phenotypically screened 13 human pancreatic adenocarcinoma (PDAC) cell lines against GEM in combination with 146 clinical inhibitors and observed strong synergy for the ATR kinase inhibitor Elimusertib in most cell lines.

Pervasive glacier retreats across Svalbard from 1985 to 2023.

A major uncertainty in predicting the behaviour of marine-terminating glaciers is ice dynamics driven by non-linear calving front retreat, which is poorly understood and modelled. Using 124919 calving front positions for 149 marine-terminating glaciers in Svalbard from 1985 to 2023, generated with deep learning, we identify pervasive calving front retreats for non-surging glaciers over the past 38 years. We observe widespread seasonal cycles in calving front position for over half of the glaciers.

Added prognostic value of sentinel lymph node mapping in endometrial cancer to molecular subgroups.

Objective: Treatment approaches for endometrial cancer became more personalized in the last decade, mainly due to two key advancements - sentinel lymph node (SLN) mapping and molecular classification. However, their prognostic interaction remains relatively unexplored.

Methods: This retrospective cohort study included patients with endometrial cancer, who underwent surgical treatment including SLN mapping at the Bern University Hospital, Switzerland.

Spermidine alleviates depression via control of the stress response.

Depression is a stress-associated disorder, and it represents a major global health issue. Its pathophysiology is complex and remains insufficiently understood, with current medications often showing limited efficacy and undesirable side effects. Here, we identify imbalanced polyamine levels and dysregulated autophagy as key components of the acute stress response in humans, and as hallmarks of chronic stress and depressive disorders.

The Use of Automated Insulin Delivery around Physical Activity and Exercise in Type 1 Diabetes: A Position Statement of the European Association for the Study of Diabetes (EASD) and the International Society for Pediatric and Adolescent Diabetes (ISPAD).

Regular physical activity and exercise (PA) are cornerstones of diabetes care for individuals with type 1 diabetes. In recent years, the availability of automated insulin delivery (AID) systems has improved the ability of people with type 1 diabetes to achieve the recommended glucose target ranges. PA provides additional health benefits but can cause glucose fluctuations, which challenges current AID systems.