Perilymph sampling in Mongolian gerbil, technical note and procedure evaluation.

Objective: The aim of this study is to detail and evaluate the surgical procedure for perilymph sampling from the cochlear apex in the Mongolian gerbil.

Design: Perilymph sampling from the cochlear apex was performed one to three time in 12 male gerbils aged 8 to 12 months via the submandibular route. 11 of them were previously implanted with intracochlear implants loaded with dexamethasone and placed in the scala tympani, the 12th was used to collect control samples.

Faster sorting algorithms discovered using deep reinforcement learning.

Fundamental algorithms such as sorting or hashing are used trillions of times on any given day. As demand for computation grows, it has become critical for these algorithms to be as performant as possible. Whereas remarkable progress has been achieved in the past, making further improvements on the efficiency of these routines has proved challenging for both human scientists and computational approaches.

Effects of subtotal pancreatectomy and long-term glucose and lipid overload on insulin secretion and glucose homeostasis in minipigs.

Introduction: Nowadays, there are no strong diabetic pig models, yet they are required for various types of diabetes research. Using cutting-edge techniques, we attempted to develop a type 2 diabetic minipig model in this study by combining a partial pancreatectomy (Px) with an energetic overload administered either orally or parenterally.

Methods: Different groups of minipigs, including Göttingen-like (GL, n = 17) and Ossabaw (O, n = 4), were developed.

Oral metformin transiently lowers post-prandial glucose response by reducing the apical expression of sodium-glucose co-transporter 1 in enterocytes.

Metformin (MET) is the most prescribed antidiabetic drug, but its mechanisms of action remain elusive. Recent data point to the gut as MET's primary target. Here, we explored the effect of MET on the gut glucose transport machinery.

Competition-level code generation with AlphaCode.

Programming is a powerful and ubiquitous problem-solving tool. Systems that can assist programmers or even generate programs themselves could make programming more productive and accessible. Recent transformer-based neural network models show impressive code generation abilities yet still perform poorly on more complex tasks requiring problem-solving skills, such as competitive programming problems.

Discovering faster matrix multiplication algorithms with reinforcement learning.

Improving the efficiency of algorithms for fundamental computations can have a widespread impact, as it can affect the overall speed of a large amount of computations. Matrix multiplication is one such primitive task, occurring in many systems-from neural networks to scientific computing routines. The automatic discovery of algorithms using machine learning offers the prospect of reaching beyond human intuition and outperforming the current best human-designed algorithms.

The challenge of HLA donor specific antibodies in the management of pancreatic islet transplantation: an illustrative case-series.

Islet transplantation is a unique paradigm in organ transplantation, since multiple donors are required to achieve complete insulin-independence. Preformed or de novo Donor Specific Antibodies (DSA) may target one or several donor islets, which adds complexity to the analysis of their impact. Adult patients with type 1 diabetes transplanted with pancreatic islets between 2005 and 2018 were included in a single-center observational study.

Innovative transdermal delivery of insulin using gelatin methacrylate-based microneedle patches in mice and mini-pigs.

Painless and controlled on-demand drug delivery is the ultimate goal for the management of various chronic diseases, including diabetes. To achieve this purpose, microneedle patches are gaining increased attention. While degradable microneedle (MN) arrays are widely employed, the use of non-dissolving MN patches remains a challenge to overcome.

Photothermal Activatable Mucoadhesive Fiber Mats for On-Demand Delivery of Insulin via Buccal and Corneal Mucosa.

Electrospun fiber mats loaded with therapeutics have gained considerable attention as a versatile tool in the biomedical field. While these bandages are largely based on fast-dissolving polymers to release the cargo, stimuli-responsive fiber mats have the advantages of providing a timely and spatially controlled drug delivery platform, which can be refilled and reused several times. These benefits make electrospun fiber patches original platforms for painless and convenient on-demand hormone release.

Long-Term Analgesia following a Single Application of Fentanyl Transdermal Solution in Pigs.

Introduction: In animal research, obtaining efficient and constant pain control is regulatory but challenging. The gold standard pain management consists of opioid analgesic administration, such as buprenorphine or fentanyl extended-release patches. However, as in all drugs with a short half-life time, repeated buprenorphine administrations are needed, leading to multiple injections that affect the research protocol.

Characterization of one anastomosis gastric bypass and impact of biliary and common limbs on bile acid and postprandial glucose metabolism in a minipig model.

The alimentary limb has been proposed to be a key driver of the weight-loss-independent metabolic improvements that occur upon bariatric surgery. However, the one anastomosis gastric bypass (OAGB) procedure, consisting of one long biliary limb and a short common limb, induces similar beneficial metabolic effects compared to Roux-en-Y Gastric Bypass (RYGB) in humans, despite the lack of an alimentary limb. The aim of this study was to assess the role of the length of biliary and common limbs in the weight loss and metabolic effects that occur upon OAGB.

Mastering Atari, Go, chess and shogi by planning with a learned model.

Constructing agents with planning capabilities has long been one of the main challenges in the pursuit of artificial intelligence. Tree-based planning methods have enjoyed huge success in challenging domains, such as chess and Go, where a perfect simulator is available. However, in real-world problems, the dynamics governing the environment are often complex and unknown.

Ten-Year Outcome of Islet Alone or Islet After Kidney Transplantation in Type 1 Diabetes: A Prospective Parallel-Arm Cohort Study.

Objective: The long-term outcome of allogenic islet transplantation is unknown. The aim of this study was to evaluate the 10-year outcome of islet transplantation in patients with type 1 diabetes and hypoglycemia unawareness and/or a functioning kidney graft.

Research Design And Methods: We enrolled in this prospective parallel-arm cohort study 28 subjects with type 1 diabetes who received islet transplantation either alone (ITA) or after a kidney graft (IAK).

The GLP1R Agonist Liraglutide Reduces Hyperglucagonemia Induced by the SGLT2 Inhibitor Dapagliflozin via Somatostatin Release.

The newest classes of anti-diabetic agents include sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor (GLP1R) agonists. The SGLT2 inhibitor dapagliflozin reduces glucotoxicity by glycosuria but elevates glucagon secretion. The GLP1R agonist liraglutide inhibits glucagon; therefore, we hypothesize that the cotreatment of dapagliflozin with liraglutide could reduce hyperglucagonemia and hyperglycemia.

Preclinical Assessment of Leptin Transport into the Cerebrospinal Fluid in Diet-Induced Obese Minipigs.

Objective: A minipig model was employed to explore the changes in endogenous leptin transport into the central nervous system and in hypothalamic sensitivity to exogenous leptin when individuals are placed on high-fat diet (HFD) compared with standard diet.

Methods: Serum and cerebrospinal fluid (CSF) leptin concentrations during 10 weeks of HFD versus standard diet and exogenous leptin-induced STAT3 phosphorylation in the hypothalamus of minipigs were assessed, and the hypothalamic leptin-sensitive cells were characterized by immunofluorescence.

Results: The efficiency of the passage of endogenous blood-borne leptin into the CSF (measured as the log [CSF:serum leptin ratio]) decreased over time in minipigs fed a HFD (β = -0.

A general reinforcement learning algorithm that masters chess, shogi, and Go through self-play.

The game of chess is the longest-studied domain in the history of artificial intelligence. The strongest programs are based on a combination of sophisticated search techniques, domain-specific adaptations, and handcrafted evaluation functions that have been refined by human experts over several decades. By contrast, the AlphaGo Zero program recently achieved superhuman performance in the game of Go by reinforcement learning from self-play.

Single Low Dose of Human Recombinant Antithrombin (ATryn) has no Impact on Endotoxin-Induced Disseminated Intravascular Coagulation: An Experimental Randomized Open Label Controlled Study.

Background: Antithrombin (AT) III physiological levels are decreased during septic shock and supplementation therapy could therefore be beneficial.

Objective: We hypothesized that the use of recombinant human AT could reduce disseminated intravascular coagulation (DIC) occurrence.

Methods: We conducted a randomized open label controlled experimental study.

Incidence of postoperative delirium in elderly ambulatory patients: A prospective evaluation using the FAM-CAM instrument.

Background: While the incidence of postoperative delirium is high in aged hospitalized patients undergoing major surgery, little is known concerning patients undergoing ambulatory surgery.

Objective: To determine the incidence of postoperative delirium in aged patients after hospital discharge from an ambulatory surgery unit.

Design: Prospective observational study.

Safety of Islet Autotransplantation After Pancreatectomy for Adenocarcinoma.

Background: Total pancreatectomy with intraportal islet autotransplantation (TPIAT) rather than partial pancreatectomy could represent a major shift in the management of patients with resectable pancreatic ductal adenocarcinoma (PDAC) when risks of postoperative pancreatic fistula are well identified. This approach provides a theoretical risk of tumor cell dissemination when islet cells are transplanted into the portal vein. Our objective was to explore the safety of TPIAT in PDAC in a mouse preclinical model of subcutaneous xenotransplantation of human cells isolated from pancreatic specimen during partial pancreatectomy performed for PDAC.

Arterial Pulsatility and Circulating von Willebrand Factor in Patients on Mechanical Circulatory Support.

Background: The main risk factor for bleeding in patients with continuous-flow mechanical circulatory support (CF-MCS) is the acquired von Willebrand factor (VWF) defect related to the high shear-stress forces developed by these devices. Although a higher bleeding rate has been reported in CF-MCS recipients who had reduced pulsatility, the relation between pulsatility and the VWF defect has never been studied.

Objectives: The purpose of this study was to investigate the relation between pulsatility and VWF under CF-MCS.

Increased postprandial glucagon-like peptide-1 (GLP-1) production after endoscopic gastrointestinal bypass using the Cousin lumen-apposing stent in a porcine model.

Unlabelled: BACKGROUND AND STUDY AIMS : Endoscopic techniques have demonstrated their effectiveness in metabolic surgery, notably through a gastrointestinal (GI) liner, with a less invasive approach than conventional surgery. Our study evaluates the safety and efficacy of endoscopic GI anastomosis (EGIA) using a lumen-apposing stent to secure the anastomosis. MATERIALS AND METHODS : EGIA was performed using the transgastric approach with a two-channel endoscope with a novel stent (Cousin Biotech).

Multiparous Ewe as a Model for Teaching Vaginal Hysterectomy Techniques.

Background: Despite being linked to improving patient outcomes and limiting costs, the use of vaginal hysterectomy is on the wane. Although a combination of reasons might explain this trend, one cause is a lack of practical training. An appropriate teaching model must therefore be devised.