KRAS-mediated upregulation of CIP2A promotes suppression of PP2A-B56α to initiate pancreatic cancer development.

Oncogenic mutations in KRAS are present in ~95% of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) and are considered the initiating event of pancreatic intraepithelial neoplasia (PanIN) precursor lesions. While it is well established that KRAS mutations drive the activation of oncogenic kinase cascades during pancreatic oncogenesis, the effects of oncogenic KRAS signaling on regulation of phosphatases during this process is not fully appreciated. Protein Phosphatase 2A (PP2A) has been implicated in suppressing KRAS-driven cellular transformation and low PP2A activity is observed in PDAC cells compared to non-transformed cells, suggesting that suppression of PP2A activity is an important step in the overall development of PDAC.

DKN-01 in Combination With Tislelizumab and Chemotherapy as First-Line Therapy in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: DisTinGuish.

Purpose: The outcomes of anti-PD-1 agents plus fluoropyrimidine/platinum in frontline advanced gastroesophageal adenocarcinomas (aGEAs) remain poor. We investigated the safety, tolerability, and activity of fluoropyrimidine/oxaliplatin and tislelizumab with the DKK1-neutralizing antibody DKN-01 in aGEAs in a phase IIa open-label study.

Patients And Methods: Patients had untreated human epidermal growth factor receptor 2-negative aGEAs, RECIST v1.

Observation of Le Sage gravity analog in complex plasma.

Fragmentation of a suspension of micron-sized plastic microparticles and their contraction into dense globules was experimentally obtained in a gas discharge plasma, when the plasma density was deliberately and abruptly increased. The globules took up spherical shapes 0.14-1.

Measuring non-events: infertility estimation using cross-sectional, population-based data from four countries in sub-Saharan Africa.

Study Question: Does the prevalence of 12-month infertility in Burkina Faso, Côte d'Ivoire, Kenya, and Uganda differ between women trying to conceive and the broader population of women exposed to unprotected sex, and how are prevalence estimates affected by model assumptions and adjustments?

Summary Answer: Estimates of 12-month infertility among tryers ranged from 8% in Burkina Faso to 30% in Côte d'Ivoire, increasing substantially among a larger population of women exposed to unprotected intercourse.

What Is Known Already: While having a child is a fundamental human experience, the extent to which women and couples experience infertility is a neglected area of research, particularly in sub-Saharan Africa. Existing estimates of infertility in this region vary widely from 2% to 32%, however, potential impacts of variability in study populations and model assumptions have not been well-examined.

Endoscopic Management of Biliary and Pancreatic Pathologies in Roux-en-Y Gastric Bypass Patients: Development of a Treatment Algorithm Based on 9-Year Experience.

Background: Management of biliopancreatic pathology in Roux-en-Y gastric bypass (RYGB) patients is challenging despite the availability of multiple approaches like single-balloon enteroscopy-assisted ERCP (SBE-ERCP), laparoscopy-assisted ERCP (LA-ERCP), and EUS-directed transgastric intervention (EDGI). We evaluated the outcomes of the interchangeable combination of endoscopic procedures to treat biliopancreatic pathology in RYGB patients.

Materials And Methods: This is a monocentric retrospective study of consecutive RYGB patients with biliopancreatic pathology between June 2014 and September 2023.