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Our findings highlight a specific role of DCLK1-kinase dependent cargo selection for sEVs and shed new light on its role as a regulator of signaling in gastric tumorigenesis.Despite newly available treatments for spinal muscular atrophy (SMA), novel circulating biomarkers are still critically necessary to track SMA progression and therapeutic response. To identify potential biomarkers, we performed whole-blood RNA sequencing analysis in SMA type 1 subjects under 1 year old and age-matched healthy controls. Our analysis revealed the Heat Shock Protein Family A Member 7 (HSPA7)/heat shock 70kDa protein 7 (HSP70B) as a novel candidate biomarker to track SMA progression early in life. Changes in circulating HSP70B protein levels were associated with changes in circulating neurofilament levels in SMA newborns and infants. Future studies will determine whether HSP70B levels respond to molecular therapies.

Skeletal muscle (SkM) abnormalities may impact exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). We sought to quantify differences in SkM oxidative phosphorylation capacity (OxPhos), fibre composition, and the SkM proteome between HFpEF, hypertensive (HTN), and healthy participants.

Fifty-nine subjects (20 healthy, 19 HTN, and 20 HFpEF) performed a maximal-effort cardiopulmonary exercise test to define peak oxygen consumption (VO

), ventilatory threshold (VT), and VO

efficiency (ratio of total work performed to O

consumed). SkM OxPhos was assessed using Creatine Chemical-Exchange Saturation Transfer (CrCEST, n=51), which quantifies unphosphorylated Cr, before and after plantar flexion exercise. The half-time of Cr recovery (t

) was taken as a metric of in vivo SkM OxPhos. In a subset of subjects (healthy=13, HTN=9, and HFpEF=12), percutaneous biopsy of the vastus lateralis was performed for myofibre typing, mitochondrial morphology, and proteomic and phosphSkM may contribute to exercise intolerance in HFpEF.Cyclic AMP-dependent protein kinase A (PKA) and protein phosphatase 1 (PP1) are proteins involved in numerous essential signalling pathways that modulate physiological and pathological functions. Both PP1 and PKA can be inhibited by dopamine- and cAMP-regulated phosphoprotein 32 kD (DARPP-32). Using immunohistochemistry, PKA and PP1 expression was determined in a large primary breast tumour cohort to evaluate associations between clinical outcome and clinicopathological criteria (n > 1100). In addition, mRNA expression of PKA and PP1 subunits was assessed in the METABRIC data set (n = 1980). Low protein expression of PKA was significantly associated with adverse survival of breast cancer patients; interestingly, this relationship was stronger in ER-positive breast cancer patients. PP1 protein expression was not associated with patient survival. PKA and PP1 subunit mRNA was also assessed; PPP1CA, PRKACG and PRKAR1B were associated with breast cancer-specific survival. In patients with high expression of DARPP-32, low expression of PP1 was associated with adverse survival when compared to high expression in the same group. PKA expression and PP1 expression are of significant interest in cancer as they are involved in a wide array of cellular processes, and these data indicate PKA and PP1 may play an important role in patient outcome.

To meet the demands imposed by the continuing growth of the Age-related macular degeneration (AMD) patient population, automation of follow-ups by detecting retinal oedema using deep learning might be a viable approach. However, preparing and labelling data for training is time consuming. In this study, we investigate the feasibility of training a convolutional neural network (CNN) to accurately detect retinal oedema on optical coherence tomography (OCT) images of AMD patients with labels derived directly from clinical treatment decisions, without extensive preprocessing or relabelling.

A total of 50439 OCT images with associated treatment information were retrieved from databases at the Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark between 01.06.2007 and 01.06.2018. A CNN was trained on the retrieved data with the recorded treatment decisions as labels and validated on a subset of the data relabelled by three ophthalmologists to denote presence of oedema.

Moderate inter-grader agreemts might encourage the use of existing clinical databases for development of deep learning based algorithms without labour-intensive preprocessing in the future.

This study aimed to determine the clinical presentation, management and outcomes for patients with ileoanal pouch cancer.

Patients who were diagnosed with ileoanal pouch cancer were identified from our polyposis registry (1978-2019) and operative and referral records (2006-2019). Details of presentation, endoscopic surveillance, cancer staging and management were retrieved from hospital records.

Eighteen patients were identified (12 with ulcerative colitis, one with Crohn's disease, three with familial adenomatous polyposis [FAP], two with dual diagnosis of FAP and inflammatory bowel disease). The median time from pouch formation to cancer diagnosis was 16.5years (range 5-34years) and the median age of the patient at pouch cancer diagnosis was 54years (range 35-71years). Eleven of the 18 patients were undergoing surveillance. Four of five FAP patients developed pouch cancer whilst on surveillance. Eight patients were asymptomatic at the time of pouch cancer diagnosis. Two patients had complete clinical response following chemoradiotherapy. TGF-beta tumor Fourteen patients underwent pouch excision surgery (eight with exenteration). Median survival was 54months; however, only eight patients had outcomes available beyond 24months follow-up.

Pouch cancer can occur in patients despite routine surveillance and without symptoms, and survival is poor. Centralization of 'high-risk' patients who require surveillance is recommended and a low threshold for referral to centres that can provide expert investigation and management is advised.

Pouch cancer can occur in patients despite routine surveillance and without symptoms, and survival is poor. Centralization of 'high-risk' patients who require surveillance is recommended and a low threshold for referral to centres that can provide expert investigation and management is advised.Biology is a data-driven discipline facilitated greatly by computer programming skills. This article describes an introductory experiential programming activity that can be integrated into distance learning environments. Students are asked to develop their own Python programs to identify the nature of alleles linked to disease. This activity effectively engages students in a problem solving exercise that provides an opportunity for application of basic programming skills as well as understanding eukaryotic gene structure. We provide sets of mapped alleles for two well-known genes, CFTR and HFE, as well as a suite of relevant Python programs to achieve these outcomes or allow subsequent exercise modifications.

The faecal immunochemical test (FIT) is currently utilized in both symptomatic and screening populations, but little is known about factors that affect its performance. For example, proton pump inhibitor (PPI) therapy has been purported to increase false negative rates. This has significant implications given the extent of PPI prescriptions. The aim of this work was to evaluate the performance of the FIT for the detection of colorectal neoplasms and the impact of PPI therapy on its diagnostic accuracy.

Symptomatic patients referred on the suspected cancer pathway and those on polyp surveillance between 2015 and 2019 were approached to participate. Estimates of the accuracy of FIT at different cut-off levels in diagnosing colorectal neoplasms were made. Logistic regression was used to assess the effect of PPIs on the FIT results.

A total of 667 participants were eligible for the final analysis. At a cut-off of 10μg/g faeces, the overall sensitivity and specificity of FIT for the detection of colorectal cancer (CRC) was 0.85 (95% CI 0.71-0.94) and 0.81 (95% CI 0.78-0.84), respectively. For the detection of advanced neoplasia, the sensitivity was 0.70 (95% CI 0.58-0.79) and the specificity was 0.83 (95% CI 0.80-0.86). At higher thresholds, the sensitivity steadily declined whilst specificity increased. PPI therapy did not have a significant effect on performance of the FIT.

FIT is a good rule-out test for the detection of CRC and advanced neoplasia at lower thresholds. PPI therapy does not appear to have an effect on its diagnostic performance.

FIT is a good rule-out test for the detection of CRC and advanced neoplasia at lower thresholds. PPI therapy does not appear to have an effect on its diagnostic performance.Transcranial magnetic stimulation (TMS) has become one of the major tools for establishing the causal role of specific brain regions in perceptual, motor, and cognitive processes. Nevertheless, a persistent limitation of the technique is the lack of clarity regarding its precise effects on neural activity. Here, we examined the effects of TMS intensity and frequency on concurrently recorded blood-oxygen-level-dependent (BOLD) signals at the site of stimulation. In two experiments, we delivered TMS to the dorsolateral prefrontal cortex in human subjects of both sexes. In Experiment 1, we delivered a series of pulses at high (100% of motor threshold) or low (50% of motor threshold) intensity, whereas, in Experiment 2, we always used high intensity but delivered stimulation at four different frequencies (5, 8.33, 12.5, and 25 Hz). We found that the TMS intensity and frequency could be reliably decoded using multivariate analysis techniques even though TMS had no effect on the overall BOLD activity at the site of stimulation in either experiment. These results provide important insight into the mechanisms through which TMS influences neural activity.

Central post-stroke pain (CPSP) has a detrimental effect on the quality of life of post-stroke patients. However, no definitive and effective method has been established yet for the treatment of CPSP.

We aimed to examine the applicability of single-injection peripheral nerve blocks (PNBs) for the treatment of CPSP.

In this retrospective study, we included 22 patients (mean age = 56.3years; 13 men and 9 women) diagnosed with CPSP who visited an outpatient rehabilitation clinic in Seoul National University Bundang Hospital between December 2018 and April 2020.

The patients underwent ultrasound-guided single-injection PNB (lidocaine+epinephrine [1 200,000]) according to the primary site of pain. The level of pain (measured using a numeric rating scale) was recorded before and after the PNB, and the occurrence of adverse events were also measured. The primary outcome of this study was the amount of pain reduction after PNB. Secondary outcome measures obtained 1month after the PNB included the pain reduction rate 1month after the PNB, the patient-reported satisfaction and effectiveness regarding the PNB, intention for re-injection, and the patients' willingness to recommend this procedure to others.

The mean pain reduction after PNB was 3.3±2.8. PNB was associated with pain reduction that persisted for greater than 1month in 68% (15/22) of the patients. Thirteen of 22 patients reported a pain reduction of 50% or more. The mean pain reduction rate was 43.6%. Of the 22 patients, 13 were willing to undergo a second round of treatment with PNB. Nine of them underwent the procedure. No adverse events were observed in this study.

Our study provides preliminary data suggesting that PNB could be an effective and feasible method to treat CPSP.

Our study provides preliminary data suggesting that PNB could be an effective and feasible method to treat CPSP.