RenaSci (United Kingdom)

Intraoperative rapid diagnosis with pathological classification by pathologists plays a pivotal role in making appropriate surgical decisions.However, morphological evaluation of intraoperative frozen sections is apparently more difficult than that of formalin fixed paraffin embedded (FFPE) tissue because of their unavoidable tissueprocessing artifacts, which compels pathologists, even well-trained, more challenging to make an accurate diagnosis.Therefore, assisting the pathological diagnosis with artificial intelligence is anticipated.Here, we built the data set consisting of histopathological micrographs of intraoperative frozen sections and demonstrated an automatic breast carcinoma detection model based on a Single Shot Multibox Detector, an object detection method known for real-time, high-speed performance.The final 3-class classification model was trained on 943 intraoperative frozen section images and evaluated using 65 images, identifying benign lesions, non-invasive carcinoma, and invasive carcinoma.The 2-class (benign or malignant) and 3-class classification tasks achieved diagnostic accuracies for whole image of 92.3% and 89.2%, respectively.When we evaluated the performance of object detection in the 2-class task, the precision, recall and F1 scores for malignant detection are 70.3%, 74.4%, and 72.3%, respectively.Additionally, the model's object detection performance was assessed using FFPE images, yielding a precision of 55.1%, a sensitivity of 76.9%, and an F1 score of 64.2%, suggesting that it is particularly well-suited for intraoperative frozen sections.In conclusion, we presented the automatic breast carcinoma detection method, utilizing histopathological micrographs of intraoperative frozen sections.The present model may assist pathologists by reducing their workload and minimizing the risk of overlooking carcinoma cells in intraoperative diagnosis.

Sustainable territorial development, management of the built environment, and the right to housing are directly related, based on a holistic view of sustainability in our cities, as urban sustainability concerns a set of environmental, economic, and social factors. Thinking about sustainable cities means thinking about development and guaranteeing the right to the city and housing for all, so that the use of natural resources is rational, based on preservation and climate justice. This article[1] seeks to analyze one of the largest urban occupations in the interior of São Paulo, the Renascer Community, an area of extreme social and environmental vulnerability, in which around 300 families live without minimum urban infrastructure and basic sanitation. The product of this study will be a survey of the area, carrying out a permacultural project as a proposal for environmental recovery of the degraded area and self-management of the community, based on the circular economy. In addition, urban planning guidelines will also be proposed that seek to work in an integrated manner with the permacultural project to provide an urban infrastructure capable of meeting the community's needs and promoting territorial development. [1] This article is based on the results of the author's undergraduate thesis.

Polymorphisms in the region of the calmodulin-dependent kinase isoform D (CaMK1D) gene are associated with increased incidence of diabetes, with the most common polymorphism resulting in increased recognition by transcription factors and increased protein expression. While reducing CaMK1D expression has a potentially beneficial effect on glucose processing in human hepatocytes, there are no known selective inhibitors of CaMK1 kinases that can be used to validate or translate these findings. Here we describe the development of a series of potent, selective, and drug-like CaMK1 inhibitors that are able to provide significant free target cover in mouse models and are therefore useful as in vivo tool compounds. Our results show that a lead compound from this series improves insulin sensitivity and glucose control in the diet-induced obesity mouse model after both acute and chronic administration, providing the first in vivo validation of CaMK1D as a target for diabetes therapeutics.

Adult, female rats given irregular, limited access to chocolate develop binge-eating behaviour with normal bodyweight and compulsive/perseverative and impulsive behaviours similar to those in binge-eating disorder. We investigated whether (a) dysregulated central nervous system dopaminergic and opioidergic systems are part of the psychopathology of binge-eating and (b) these neurotransmitter systems may mediate the actions of drugs ameliorating binge-eating disorder psychopathology. Binge-eating produced a 39% reduction of striatal D1 receptors with 22% and 23% reductions in medial and lateral caudate putamen and a 22% increase of striatal μ-opioid receptors. There was no change in D1 receptor density in nucleus accumbens, medial prefrontal cortex or dorsolateral frontal cortex, striatal D2 receptors and dopamine reuptake transporter sites, or μ-opioid receptors in frontal cortex. There were no changes in ligand affinities. The concentrations of monoamines, metabolites and estimates of dopamine (dopamine/dihydroxyphenylacetic acid ratio) and serotonin/5-hydroxyindolacetic acid ratio turnover rates were unchanged in striatum and frontal cortex. However, turnover of dopamine and serotonin in the hypothalamus was increased ~20% and ~15%, respectively. Striatal transmission via D1 receptors is decreased in binge-eating rats while μ-opioid receptor signalling may be increased. These changes are consistent with the attenuation of binge-eating by lisdexamfetamine, which increases catecholaminergic neurotransmission, and nalmefene, a μ-opioid antagonist.

To assess the chronic effect of the DPP-4 inhibitor, linagliptin, alone, in combination with exenatide, and during exenatide withdrawal, in diet-induced obese (DIO) rats. Female Wistar rats were exposed to a cafeteria diet to induce obesity. Animals were then dosed with vehicle or linagliptin (3 mg/kg PO) orally once-daily for a 28 day period. In a subsequent study, rats received exenatide (either 3 or 30 microg/kg/day) or vehicle by osmotic mini-pump for 28 days. In addition, groups of animals were dosed orally with linagliptin either alone or in combination with a 3 microg/kg/day exenatide dose for the study duration. In a final study, rats were administered exenatide (30 microg/kg/day) or vehicle by osmotic mini-pump for eleven days. Subsequently, exenatide-treated animals were transferred to vehicle or continued exenatide infusion for a further ten days. Animals transferred from exenatide to vehicle were also dosed orally with either vehicle or linagliptin. In all studies, body weight, food and water intake were recorded daily and relevant plasma parameters and carcass composition were determined. In contrast to exenatide, linagliptin did not significantly reduce body weight or carcass fat in DIO rats versus controls. Linagliptin augmented the effect of exenatide to reduce body fat when given in combination but did not affect the body weight response. In rats withdrawn from exenatide, weight regain was observed such that body weight was not significantly different to controls. Linagliptin reduced weight regain after withdrawal of exenatide such that a significant difference from controls was evident. These data demonstrate that linagliptin does not significantly alter body weight in either untreated or exenatide-treated DIO rats, although it delays weight gain after exenatide withdrawal. This finding may suggest the utility of DPP-4 inhibitors in reducing body weight during periods of weight gain.

We examined the effects of the oral dipeptidyl peptidase-4 (DPP-4) inhibitor saxagliptin on glycaemic control and pancreatic β-cell mass and morphology in a mouse model of type 2 diabetes mellitus (T2DM). Male C57BL/6 mice (n = 12/group) aged 4 to 6 weeks and weighing >15 g received a high-fat diet throughout this 45-day study. After a 7-day handling period, baseline levels of plasma glucose, plasma insulin and glycated haemoglobin (HbA1c) were assessed. Animals were allocated to one of six groups: compound vehicle control, intraperitoneal streptozotocin (STZ, 50 mg/kg)-treated control and saxagliptin (10 mg/kg) or sitagliptin (10 mg/kg, positive control) initiated 7 days before or 1 day after STZ administration. Endpoints included changes in body weight, food and water consumption, glucose tolerance (approximately 3 weeks post-STZ), fasting glucose and HbA1c and immunohistochemical analyses of the pancreas. Body weight, weight gain and food intake were reduced in STZ versus control mice. DPP-4 inhibitor treatment did not affect these changes, but the increase in water intake observed post-STZ administration was significantly attenuated with DPP-4 inhibitors whether initiated before or after STZ injury. Small but significant improvements in glycaemic control were observed with DPP-4 inhibitors versus the STZ control. Improved β-cell mass and morphology were observed with saxagliptin given pre- or post-STZ and sitagliptin given post-STZ. Saxagliptin mitigated damage to β-cells and improved glycaemic control in this mouse model of T2DM.