Underwoodmackinnon1317

Rap guanine nucleotide exchange factor 1 (RAPGEF1) is involved in cell adhesion and neuronal migration. Previously we found lower RAPGEF1 mRNA levels in Brodmann's area (BA) 9 in subjects with schizophrenia compared to controls. This study aimed to determine whether RAPGEF1 expression was altered in other brain regions implicated in schizophrenia and whether this was associated with suicide. Using qPCR, we measured the levels of RAPGEF1 in post-mortem BA 8 and 44 from 27 subjects with schizophrenia and 26 non-psychiatric control subjects. To address the effect of antipsychotic treatments, Rapgef1 mRNA levels were measured in the cortex from rats treated with typical antipsychotic drugs. There was no difference in RAPGEF1 normalised relative expression levels in BA 8 or 44. However, in BA 8, schizophrenia subjects had higher raw Ct RAPGEF1 levels compared to controls. There were higher RAPGEF1 levels in suicide completers compared to non-suicide schizophrenia subjects in BA 8. Rapgef1 expression levels in the rat cortex did not vary with antipsychotic treatment. Our findings suggest changes in RAPGEF1 expression may be limited to the dorsolateral prefrontal cortex from subjects with schizophrenia. Further investigation of the function of RAPGEF1 may lead to a greater understanding of the pathophysiology of schizophrenia.Problematic Internet use (PIU) behaviours involve one's maladaptive Internet use and have been often described as secondary manifestations of pre-existing psychopathology. Furthermore, different profiles of PIU sufferers have been proposed. However, little is known of the impact these may be having on treatment responses. Thus, this study aims to investigate the psychopathological profiles of those who seek treatment for PIU within a specialised public outpatient unit and whether these influence treatment outcomes. This research utilised 203 treatment seekers of the Specialized Department of Problematic Internet Use (SD-PIU) of the Psychiatric Hospital of Attica, in Greece (mean age = 26.02; SD = 7.9). To assess psychopathology, the Symptom Checklist-90 Revised (SCL-90-R) was used. Treatment responses were reported either as completed, continued, or drop out. A Latent Class/Profiling-Analysis (LCA) was performed, guided by variations across the SCL-90-R psychopathologies. It indicated two naturally occurring profiles of comorbid psychological symptoms; 66% were classified as the "High Comorbidity" (HC) and 34% as the "Low Comorbidity" (LC) profile. Regarding treatment outcomes, LC patients presented with significantly lower dropout rates and higher levels of completion. The present study poses imperative clinical implications regarding the necessity of specialized treatment planning based on the different PIU treatment seekers psychopathological comorbidities.

Adherence to medications for asthma and COPD can reduce exacerbation rates, decrease healthcare costs, and improve health-related quality of life. In spite of the advantages to treatment adherence, individuals with asthma and COPD often fail to take medicines as prescribed. The objectives of this study were to determine the extent of non-adherence with asthma and COPD medicines and to describe the reasons for non-adherence in these conditions.

Data from the National Health and Wellness Study (NHWS), a self-administered, annual, internet-based cross-sectional survey of US adults from 2018 was used. NHWS participants who self-reported taking daily prescription medication(s) to treat asthma and COPD responded to the 19 reasons for non-adherence and one global item in the Medication Adherence Reasons Scale (MAR-Scale). Frequencies were used to identify the reasons for non-adherence.

The non-adherence rate in asthma (N=2810) was 38.4% and 28.4% in COPD (N=1632). For both conditions, "simply missing the medicine" was the most common cause of non-adherence. Additionally, for both conditions, there was a difference between the non-adherence reason reported by more individuals and the reason for which the medicine was missed for the most number of days.

The MAR-Scale identified the most frequent reasons for non-adherence with asthma and COPD in a nationwide sample in the US. The MAR-Scale can be used as a tool in a clinic setting or at a population level to measure the extent and the reasons for non-adherence.

The MAR-Scale identified the most frequent reasons for non-adherence with asthma and COPD in a nationwide sample in the US. The MAR-Scale can be used as a tool in a clinic setting or at a population level to measure the extent and the reasons for non-adherence.

Detailed evaluation of bile duct (BD) is main focus during endoscopic ultrasound (EUS). The aim of this study was to develop a system for EUS BD scanning augmentation.

The scanning was divided into 4 stations. We developed a station classification model and a BD segmentation model with 10681 images and 2529 images, respectively. 1704 images and 667 images were applied to classification and segmentation internal validation. For classification and segmentation video validation, 264 and 517 videos clips were used. For man-machine contest, an independent data set contained 120 images was applied. 799 images from other two hospitals were used for external validation. A crossover study was conducted to evaluate the system effect on reducing difficulty in ultrasound images interpretation.

For classification, the model achieved an accuracy of 93.3% in image set and 90.1% in video set. For segmentation, the model had a dice of 0.77 in image set, sensitivity of 89.48% and specificity of 82.3% in video set. For external validation, the model achieved 82.6% accuracy in classification. In man-machine contest, the models achieved 88.3% accuracy in classification and 0.72 dice in BD segmentation, which is comparable to that of expert. In the crossover study, trainees' accuracy improved from 60.8% to 76.3% (P<0.01, 95% C.I. 20.9-27.2).

We developed a deep learning-based augmentation system for EUS BD scanning augmentation.

Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Hubei Province Major Science and Technology Innovation Project, National Natural Science Foundation of China.

Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Hubei Province Major Science and Technology Innovation Project, National Natural Science Foundation of China.

The establishment of patient-derived models for pancreatic ductal adenocarcinoma (PDAC) using conventional methods has been fraught with low success rate, mainly because of the small number of tumour cells and dense fibrotic stroma. Here, we sought to establish patient-derived model of PDAC and perform genetic analysis with responses to anticancer drug by using the conditionally reprogrammed cell (CRC) methodology.

We performed in vitro and in vivo tumourigenicity assays and analysed histological characteristics by immunostaining. We investigated genetic profiles including mutation patterns and copy number variations using targeted deep sequencing and copy-number analyses. We assessed the responses of cultured CRCs to the available clinical anticancer drugs based on patient responsiveness.

We established a total of 28 CRCs from patients. Of the 28 samples, 27 showed KRAS mutations in codon 12/13 or codon 61. We found that somatic mutations were shared in the primary-CRC pairs and shared mutations included key oncogenic mutations such as KRAS (9 pairs), TP53 (8 pairs), and SMAD4 (3 pairs). Overall, CRCs preserved the genetic characteristics of primary tumours with high concordance, with additional confirmation of low-AF NPM1 mutation in CRC (35 shared mutations out of 36 total, concordance rate=97.2%). CRCs of the responder group were more sensitive to anticancer agents than those of the non-responder group (P < 0.001).

These results show that a pancreatic cancer cell line model can be efficiently established using the CRC methodology, to better support a personalized therapeutic approach for pancreatic cancer patients.

2014R1A1A1006272, HI19C0642-060019, 2019R1A2C2008050, 2020R1A2C209958611, and 2020M3E5E204028211.

2014R1A1A1006272, HI19C0642-060019, 2019R1A2C2008050, 2020R1A2C209958611, and 2020M3E5E204028211.

Congenital malformations are common birth defects with high neonatal morbidity and mortality. It is essential to find simpler and more efficient biomarkers for early prenatal diagnosis. Therefore, we investigated PIWI-interacting RNAs (piRNAs) as potential prenatal biomarkers in plasma-derived exosomes from pregnant women carrying foetuses with congenital malformations.

Small RNA sequencing was used to screen piRNA biomarkers in plasma-derived exosomes of five pregnant women carrying foetuses with nonsyndromic cleft lip and palate (nsCLP) and five women carrying normal foetuses. Differentially expressed piRNAs were verified in 270 pregnant women, including 111 paired women carrying foetuses with congenital malformations and normal foetuses (at 24 gestational weeks), 10 paired women carrying foetuses with nsCLP and normal foetuses (at 15-19 gestational weeks), and 28 women at different stages of normal pregnancy. piRNA biomarkers were also verified in placentas, umbilical cords, fetal medial calf muscles, and lip tissues of nsCLP and normal foetuses.

We identified a biomarker panel of three pregnancy-associated exosomal piRNAs (hsa-piR-009228, hsa-piR-016659, and hsa-piR-020496) could distinguish nsCLP foetuses from normal foetuses. These three piRNAs had better diagnostic accuracy for nsCLP at the early gestational stage, at which time typical malformations were not detected upon prenatal ultrasound screening, and had diagnostic value for neural tube defects (NTDs) and congenital heart defects (CHDs).

Our work revealed the potential clinical applications of piRNAs for predicting nsCLP, NTDs, and CHDs.

National Key Research and Development Program, National Natural Science Foundation of China, and LiaoNing Revitalization Talents Program .

National Key Research and Development Program, National Natural Science Foundation of China, and LiaoNing Revitalization Talents Program .

The presence of no-reflow can increase the risk of major adverse cardiac events and is widely regarded as an important sign of serious prognosis. Previous studies show that laminin receptor (LR) is closely related to the morphology and function of microvessels. However, whether LR is involved in the occurrence and development of no-reflow is still unknown.

In vivo, positron emission tomography (PET) perfusion imaging was performed to detect the effects of intramyocardial gene (LR-AAV and LR-siRNA-AAV) delivery treatment on the degree of no-reflow. In vitro, LC-MS/MS analysis was conducted to identify the LR phosphorylation sites of human cardiac microvascular endothelial cells (HCMECs) treated with oxygen-glucose deprivation (OGD) for 4h. HA15 concentration Western blot analyses were used to evaluate the phosphorylation levels of LR at residues Tyr47 (phospho-Tyr47-LR/pY47-LR) and Thr125 (phospho-Thr125-LR/pT125-LR) and their effects on the phosphorylation of VE-cadherin residue Ser665 (phospho-Ser665-VE-cad).

LR over-expression, LR

(phosphonull) and LR

(phosphonull) treatments were found to reduce the level of phospho-Ser665-VE-cad, and subsequently maintain adherent junctions and endothelial barrier integrity in hypoxic environments.