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Leucine‐rich repeat kinase 2 (LRRK2) is considered a promising therapeutic target for Parkinson's disease, Crohn's disease, and cancer. Despite considerable research, none of these inhibitors are available for clinical application. Herein, we designed and synthesized novel thienopyrimidine derivatives by a bioisosteric replacement and investigated their structure–activity relationships. Thieno[3,2‐d]pyrimidine derivative 22showed the most potent inhibitory activity and inhibited both wild‐type and G2019S mutant LRRK2 with IC50values of 30 and 14 nM, respectively.

Background: There is an increased use of endoscopic thyroidectomy (ET), including robotic-assisted thyroidectomy (RT), to avoid postoperative scars on the anterior neck. The objective of this study was to compare the surgical and oncologic outcomes between ET and conventional open thyroidectomy (COT) for differentiated thyroid carcinoma (DTC). Methods: We reviewed 4129 patients with DTC who underwent thyroid lobectomy at Seoul St. Mary’s Hospital (Seoul, Korea) from January 2009 to December 2014. Patients were categorized according to the type of surgery and statistically compared using propensity score matching analysis. Results: The mean operation time was significantly longer in the ET group than in the OT group (101.2 ± 26.2 min vs. 86.4 ± 27.0 min, p< 0.001). The number of harvested lymph nodes was significantly lower in the ET group than in the OT group (5.5 ± 4.2 vs. 8.3 ± 6.2, p< 0.001). There was no significant difference in the recurrence rate between the two groups (p= 0.879). Kaplan–Meier analysis revealed no significant difference in the disease-free survival after propensity score matching (p= 0.811). The mean follow-up duration was 90.4 ± 21.0 months. Conclusions: Transaxillary ET including RT for DTC is a safe and feasible alternative to COT with a cosmetically desirable outcome. Further studies are required to confirm our results.

Purpose: Digital interventions that consider end-user needs, preferences, and concerns may address suboptimal rates of e-health uptake, usage, and engagement. We explored target-user perspectives of e-health treatment and prevention programs for eating disorders (EDs), with a focus on investigating (1) perceived advantages and barriers of e-health; (2) help-seeking intentions; and (3) preferences for different digital functionality, device types, and content-delivery formats. Methods: Survey data were analysed from 722 community-based participants. Participants were categorized into one of four groups based on symptom presentation and severity, ranging from low risk to probable bulimia nervosa or binge-eating disorder. Results: e-health advantages that received the highest endorsement (~ 84%) were “always there in times of need” and “travel not required”. e-health barriers that received the highest endorsement (~ 50%) were concerns about data privacy and the accuracy of content presented. Nearly three-quarters reported an intention to use an e-health platform for preventing or treating EDs. Preference ratings were highest for programs to be available on all digital devices (relative to restricting the program to one type of device) and for content to be presented via graphics and video tutorials (rather than audio-based). e-health functionality that received highest preference ratings (~ 80%) were added clinician support, tailored feedback, strategies to change unhelpful ED thoughts, screening scales to assess symptoms, ED psychoeducation, and just-in-time intervention prompts. Preference and intention ratings were strikingly similar across all subgroups. Conclusion: Findings may inform the development and design of e-health platforms that meet the needs of people at different stages of an ED. Level of evidence: Level V, cross-sectional descriptive study.

Regulating protein import across the endoplasmic reticulum (ER) membrane occasionally results in the synthesis of topologically unnatural variants, and their accumulation often leads to proteotoxicity. However, since this is a regulated process, it is questionable whether the topological rearrangement really has adverse consequences. In the present study, we provide an insight into the functional benefit of translocational regulation by illustrating mutant-selective topologic conversion (MSTC) and demonstrate that MSTC contributes to selective degradation of a membrane-anchored prion protein isoform (ctmPrP). We find that ctmPrP is inherently short-lived and topologically competent for degradation rather than accumulation. MSTC achieves, cotranslationally, the unique topology of ctmPrP during translocation, facilitating selective ctmPrP degradation from the ER via the proteasome-dependent pathway before entering the secretory pathway. At this time, the N-terminal polycationic cluster is essential for MSTC, and its cytosolic exposure acquires “ERAD-degron”-like activity for ctmPrP. Bypassing MSTC delays ctmPrP degradation, thus increasing prion proteotoxicity. Thus, topological rearrangement is used for the MSTC as a part of the protein quality control pathway to ensure the safety of the secretory pathway from misfolded PrP.

DT-diaphorase (DT-D) is known to mainly catalyze the two-electron reduction of quinones and nitro(so) compounds. Detection of Gram-negative bacterial outer membrane vesicles (OMVs) that contain pyrogenic lipopolysaccharides (LPSs, also called endotoxins) is required for evaluating the toxic effects of analytical samples. Here, we report that DT-D has a high dephosphorylation activity: DT-D catalyzes reductive dephosphorylation of a phosphate-containing substrate in the presence of NADH. We also report that sensitive and simple OMV detection is possible with a sandwich-type electrochemical immunosensor using DT-D and two identical LPS-binding antibodies as a catalytic label and two sandwich probes, respectively. The absorbance change in a solution containing 4-nitrophenyl phosphate indicates that dephosphorylation occurs in the presence of both DT-D and NADH. Among the three phosphate-containing substrates [4-aminophenyl phosphate, ascorbic acid phosphate, and 1-amino-2-naphthyl phosphate (ANP)] that can be converted into electrochemically active products after dephosphorylation, ANP shows the highest electrochemical signal-to-background ratio, because (i) the dephosphorylation of ANP by DT-D is fast, (ii) the electrochemical oxidation of the dephosphorylated product (1-amino-2-naphthol, AN) is rapid, even at a bare indium–tin oxide electrode, and (iii) two redox cycling processes significantly increase the electrochemical signal. The two redox cycling processes include an electrochemical–enzymatic redox cycling and an electrochemical–chemical redox cycling. The electrochemical signal in a neutral buffer (tris buffer, pH 7.5) is comparable to that in a basic buffer (tris buffer, pH 9.5). When the immunosensor is applied to the detection of OMV from Escherichia coli, the detection limit is found to be 8 ng/mL. This detection strategy is highly promising for the detection of biomaterials, including other extracellular vesicles.

CT radiation is arguably carcinogenic. Results from single-centre studies, mostly retrospective, have advocated lowering the CT radiation dose for the diagnosis of appendicitis. However, adoption of low-dose CT has been slow. We aimed to assess the effectiveness of low-dose CT compared with standard-dose CT in the diagnosis of appendicitis in adolescents and young adults.

The effort to reduce carbon dioxide emissions has become an important issue in a variety of fields, including urban systems. Hence, a more detailed planning policy, with appropriate approaches to evaluation, is necessary to determine the future urban spatial structure. In this paper, we utilize geographic information system (GIS) to estimate the travel times for journeys undertaken by automobiles and subway systems, and a modal split model is proposed to estimate the modal share. Then, the reduction ratio of carbon dioxide emissions is evaluated by assessing several scenarios intended to determine the best policy directions for reorganizing the urban spatial structure, with the aim of lowering the environmental impacts. As a result, a reduction of carbon dioxide emissions could be achieved in the following ways: (1) long distance commutes could be reduced by increasing residential spaces where jobs are plentiful, (2) areas where accessibility to stations is good and also where the modal share of subways is high should be given priority for development, and (3) commutes could be decreased by improving the jobs–housing balance.

Transaxillary robotic thyroidectomy is considered a technically feasible and safe treatment option for patients with low-risk papillary thyroid carcinoma (PTC). The aim of the present study was to determine the factors that contribute to the perioperative surgical outcomes of robotic thyroidectomy and to suggest guidelines for patient selection to be used by surgeons inexperienced in the technique. We reviewed the records of 275 patients with PTC who underwent robotic total thyroidectomy using a gasless, transaxillary single-incision approach at Yonsei University Health System, South Korea, between January 2011 and May 2012. The association between surgical outcomes and clinicopathologic factors was assessed using linear and logistic regression analysis. The contributing factors for surgical outcomes of robotic thyroidectomy were categorized as patient factors, including gender and body mass index (BMI), and thyroid-specific factors, including thyroid gland size, coexistent thyroiditis, tumor size, and serum anti-thyroglobulin antibody and anti-microsomal antibody titers. Of these, male gender, a large thyroid gland, and thyroiditis significantly increased the total operation time. Male gender, thyroiditis, and overweight BMI increased the working space time, and a large thyroid gland and overweight BMI affected the console time. A large thyroid gland and histological thyroiditis were associated with increased intraoperative blood loss. There was no association between postoperative complications and clinicopathologic parameters. Male gender, overweight BMI, a large thyroid gland, and coexistent thyroiditis adversely affected the surgical outcome of robotic thyroidectomy. Surgeons inexperienced in the technique should avoid or carefully approach individuals with these factors.

Using the da Vinci®robotic system, surgeons can complete secure thyroidectomy without noticeable neck scarring. This study compared the surgical completeness of transaxillary robotic thyroidectomy (RT) with conventional open procedures (OT) in treating papillary thyroid carcinoma (PTC) patients. From April 2009 through February 2011, 94 PTC patients underwent total thyroidectomy with central compartment neck dissection (CCND) at Yonsei University College of Medicine. All patients received 1.1 GBq radioactive iodine (RAI) ablation, post-therapy whole-body scans (TxWBS), and diagnostic WBS (DxWBS) 1 year later. We prospectively compared patient clinicopathologic characteristics and surgical completeness between the two groups. Fifty-one patients underwent OT and 43 underwent RT. Mean age was significantly younger in the RT group. Tumor size, capsular-invasion frequency, multifocality, bilaterality, and central nodal metastasis were not different between the two groups. The number of retrieved nodes during CCND did not significantly differ between the groups. There was no significant difference between the OT and RT groups in stimulated thyroglobulin levels acquired during TxWBS and DxWBS. The RAI uptake ratios at TxWBS were significantly higher in the RT group compared with the OT group; however, follow-up DxWBS showed no difference in RAI uptake ratios. Also, the ablation success rate was similar between the two groups. There were no abnormal findings in follow-up neck ultrasonography in either group. Remnant thyroid tissue ablation after transaxillary RT was successfully managed by 1.1 GBq RAI. RT showed similar surgical completeness versus conventional OT, and provides a safe and feasible surgical option for PTC patients.

Robotic applications have achieved safe and precise thyroidectomy with notable cosmetic and functional benefits. This study was designed to document the influence of body habitus on robotic thyroidectomy in papillary thyroid carcinoma (PTC) patients.From July 2009 to February 2010, 352 patients underwent robotic thyroidectomy using a gasless, transaxillary single-incision approach at Yonsei University Health System. Body habitus was described using body mass index category (normal weight, overweight, obese), neck length, shoulder width, and shoulder width to neck length ratios. The impact of body habitus on surgical outcomes was analyzed with respect to operation time, number of retrieved central nodes, bleeding amount, and postoperative complications.Of the 352 patients, 217 underwent less than total thyroidectomy and 135 underwent total thyroidectomy. Operative variables (i.e. operation times, bleeding amounts, and numbers of retrieved central nodes) showed no significant differences between three BMI groups for less than total thyroidectomy. However, total operation and working space times were longer for obese patients during total thyroidectomy. In particular, shoulder width was positively correlated with total operation time, working space time, console time, and number of retrieved central nodes. On the other hand, postoperative complications were not significantly different in the three BMI groups and showed no significant correlation with the other indices of body habitus.Standardized robotic thyroidectomy can be performed safely and feasibly in patients with a large body habitus despite longer operation times.