Experimental and numerical investigation on the reinforced concrete boundary beam-wall system subjected to axial compression.

This paper proposes a reinforced concrete (RC) boundary beam-wall system that requires less construction material and a smaller floor height compared to the conventional RC transfer girder system. The structural performance of this system subjected to axial compression was evaluated by performing a structural test on four specimens of 1/2 scale. In addition, three-dimensional nonlinear finite element analysis was also performed to verify the effectiveness of the boundary beam-wall system. Three test parameters such as the lower wall length-to-upper wall length ratio, lower wall thickness, and stirrup details of the lower wall were considered. The load-displacement curve was plotted for each specimen and its failure mode was identified. The test results showed that decrease in the lower wall length-to-upper wall length ratio significantly reduced the peak strength of the boundary beam-wall system and difference in upper and lower wall thicknesses resulted in lateral bending caused by eccentricity in the out-of-plane direction. Additionally, incorporating cross-ties and reducing stirrup spacing in the lower wall significantly improved initial stiffness and peak strength, effectively minimizing stress concentration.

Structural performance of the concrete-filled tube column with internal triangular units subjected to axial compression.

This study introduces a novel concrete-filled tube (CFT) column system featuring a steel tube comprised of four internal triangular units. The incorporation of these internal triangular units serves to reduce the width-thickness ratio of the steel tube and augment the effective confinement area of the infilled concrete. This design enhancement is anticipated to result in improved structural strength and ductility, contributing to enhanced overall performance and sustainability. To assess the effectiveness of the newly proposed column system, a full-scale test was conducted on five square steel tube column specimens subjected to axial compression. Among these specimens, two adhered to the conventional steel tube column design, while the remaining three featured the new CFT columns with internal triangular units. The shape of the CFT column, the presence of infilled concrete and the presence of openings on the ITUs were considered as test parameters. The test results reveal that the ductility of the newly proposed CFT column system exhibited a minimum 30% improvement compared to the conventional CFT column. In addition, the initial stiffness and axial compressive strength of the new system were found to be comparable to those of the conventional CFT column.

Risk Factors and Trends in Adolescent's Suicide Attempt Rates Before and After the Coronavirus Disease 2019 Pandemic.

BACKGROUND: Understanding adolescents' mental health during the coronavirus disease 2019 (COVID-19) pandemic and identifying those most at risk is an urgent public health challenge. This study explored the trend of suicide attempts and the association between loneliness, family financial stress, and suicide attempts during the COVID-19 pandemic among adolescents. METHODS: Data of the 2020 to 2022 Korea Youth Risk Behavior Surveys for adolescents aged 13-18 years were used. Multivariate logistic regression analyses were performed to examine the association between suicide attempts, family financial stress, and loneliness during the COVID-19 pandemic. RESULTS: The trend of suicide attempt rates was lowest in 2020 (1.9%, 1,034 out of 53,534) and it showed an increasing trend with rates of 2.2% (1,159 out of 53,445) in 2021 and 2.5% (1,271 out of 50,455) in 2022. The risk of suicide attempt was higher among adolescents who experienced financial stress (in 2020: adjusted odds ratio [AOR], 1.53, 95% confidence interval [CI], 1.26-1.88; in 2021: AOR, 1.63, 95% CI, 1.03-1.54) and felt lonely (in 2020: AOR, 2.19, 95% CI, 1.78-2.70; in 2021: AOR, 2.65, 95% CI, 2.16-3.26; in 2022: AOR, 1.3, 95% CI, 1.04-1.55) than those who did not. CONCLUSION: The COVID-19 pandemic affected the suicide attempts of adolescents, with financial stress and feelings of loneliness closely linked to this impact. Although the pandemic nears its end, the persistent risk of suicide attempts among adolescents remains a concern. Therefore, it is imperative to implement targeted screening and interventions to address adolescent suicide risk.

Exploring Differences in Home Modification Strategies According to Household Location and Occupant Disability Status: 2019 American Housing Survey Analysis.

Home modification is essential in helping older adults age in place safely and independently. The purpose of this study was to examine the impact of housing location and disability status on home modification projects among older adults using the 2019 American Housing Survey Data. The study found that recent home modification strategies were significantly different according to older adults' housing locations and health status. Older adults in non-metropolitan areas and with disability were less likely to make home modifications, and when they did so, they spent less money on the modifications. The findings highlight the importance of providing adequate home modification programs and resources for home modifications, as well as support and education from community organizations, particularly for older adults in non-metropolitan areas. The results of this study can assist in developing housing policies and guidelines to address these current and future challenges in home modification implementation for the aging population.

Navigating the Maze: Caregivers Perception on Design Elements to Improve Wayfinding for Older Adults With Dementia in Long-Term Care Facilities.

AIM: The main purpose of this research is to understand the wayfinding experience of older adults with dementia in long-term care facilities and identifying environmental design elements that support older adults' spatial abilities. BACKGROUND: Wayfinding problems are the earliest symptoms of dementia, and older adults with cognitive impairment are more likely to get lost in the community and consequences cause psychological responses such as insecurity, agitation, and falling in their environment. METHOD: The research used data collected from 30 caregivers of two long-term care facilities in the Midwest through a survey and interview on their perceptions of wayfinding design elements. RESULTS: The research findings highlighted on caregivers' perception on wayfinding experience of older adults with dementia. The findings show a significant difference between importance and satisfaction on floor pattern and visibility in the facilities. Study indicated that glass partitions in the middle of the hall and corridor can create visual obstruction for older adults and barrier for staff as well to keep visual track on them. The qualitative study revealed that different colored doors for individual patient room in a memory care enhance older adults' wayfinding abilities. In addition, in case of multisensory stimuli, noise and smell can improve their wayfinding abilities as well. CONCLUSION: The conclusion of the study highlights the importance of understanding the design elements that can be effective in creating a safer environment for older adults with dementia.

Insular and Striatal Correlates of Uncertain Risky Reward Pursuit in Schizophrenia.

BACKGROUND AND HYPOTHESIS: Risk-taking in specific contexts can be beneficial, leading to rewarding outcomes. Schizophrenia is associated with disadvantageous decision-making, as subjects pursue uncertain risky rewards less than controls. However, it is unclear whether this behavior is associated with more risk sensitivity or less reward incentivization. Matching on demographics and intelligence quotient (IQ), we determined whether risk-taking was more associated with brain activation in regions affiliated with risk evaluation or reward processing. STUDY DESIGN: Subjects (30 schizophrenia/schizoaffective disorder, 30 controls) completed a modified, fMRI Balloon Analogue Risk Task. Brain activation was modeled during decisions to pursue risky rewards and parametrically modeled according to risk level. STUDY RESULTS: The schizophrenia group exhibited less risky-reward pursuit despite previous adverse outcomes (Average Explosions; F(1,59) = 4.06, P = .048) but the comparable point at which risk-taking was volitionally discontinued (Adjusted Pumps; F(1,59) = 2.65, P = .11). Less activation was found in schizophrenia via whole brain and region of interest (ROI) analyses in the right (F(1,59) = 14.91, P < 0.001) and left (F(1,59) = 16.34, P < 0.001) nucleus accumbens (NAcc) during decisions to pursue rewards relative to riskiness. Risk-taking correlated with IQ in schizophrenia, but not controls. Path analyses of average ROI activation revealed less statistically determined influence of anterior insula upon dorsal anterior cingulate bilaterally (left: χ2 = 12.73, P < .001; right: χ2 = 9.54, P = .002) during risky reward pursuit in schizophrenia. CONCLUSIONS: NAcc activation in schizophrenia varied less according to the relative riskiness of uncertain rewards compared to controls, suggesting aberrations in reward processing. The lack of activation differences in other regions suggests similar risk evaluation. Less insular influence on the anterior cingulate may relate to attenuated salience attribution or inability for risk-related brain region collaboration to sufficiently perceive situational risk.

HM15912, a Novel Long-Acting Glucagon-Like Peptide-2 Analog, Improves Intestinal Growth and Absorption Capacity in a Male Rat Model of Short Bowel Syndrome.

Extensive bowel resection caused by various diseases that affect the intestines, such as Crohn's disease, volvulus, and cancer, leads to short bowel syndrome (SBS). Teduglutide is the only approved glucagon-like peptide-2 (GLP-2) drug for SBS; however, it requires daily administration. A novel GLP-2 analog with a prolonged duration of action to reduce dosing frequency and promote a greater efficacy may provide patients with a better quality of life. In the present study, the sustained exposure of HM15912 was characterized in normal male rats. The efficacy of HM15912 on intestinal growth and absorption capacity was also evaluated in normal male mice, rats, and SBS rats. HM15912 exhibited a remarkably extended half-life (42.3 hours) compared with teduglutide (0.6 hours) in rats. Despite somewhat lower in vitro potency on GLP-2 receptor than human GLP-2 or teduglutide, this longer-lasting mode of action promotes HM15912 to be more effective in terms of small intestinal growth than existing GLP-2 analogs even with a less frequent dosing interval of as little as once a week in rodents, including SBS rats. Furthermore, the small intestinal weight was approximately doubled, and the D-xylose absorption was significantly increased after pre-treatment of existing GLP-2 analogs on the market or under clinical development followed by HM15912 in rodents. These results indicate that HM15912 possesses a significant small bowel trophic effect driven by continuously increased exposure, supporting that HM15912 may be a novel treatment option with greater efficacy and the longest dosing interval among existing GLP-2 analogs for SBS with intestinal failure. SIGNIFICANCE STATEMENT: HM15912, a novel long-acting glucagon-like peptide-2 (GLP-2) analog, has a significant small bowel hypertrophic effect in rodents with a reduced frequency of administration compared to the existing GLP-2 analogs on the market or currently under clinical development. This study supports the possibility that HM15912 could be administered much less frequently than other long-acting GLP-2 analogs for patients with short bowel syndrome.

Evidence of familial confounding of the association between cannabis use and cerebellar-cortical functional connectivity using a twin study.

Cerebellar-cortical resting-state functional connectivity (rsFC) has been reported to be altered in cannabis users. However, this association may be due to genetic and environmental confounding rather than a causal relationship between cannabis use and changes in rsFC. In this co-twin control study, linear mixed models were used to assess relationships between the number of lifetime cannabis uses (NLCU) and age of cannabis onset (ACO) with cerebellar-cortical rsFC. The rsFC with seven functional networks was evaluated in 147 monozygotic and 82 dizygotic twin pairs. Importantly, the use of genetically informed models in this twin sample facilitated examining whether shared genetic or environmental effects underlie crude associations between cannabis measures and connectivity. Individual-level phenotypic analyses (i.e., accounting for twin-pair non-independence) showed that individuals in the full sample with earlier ACO and higher NLCU had lower cerebellar rsFC within the VA, DA, and FP networks. Yet, there were no significant differences in cerebellar-cortical rsFC between monozygotic twins who were discordant for cannabis measures. These findings suggest shared genetic or environmental confounds contribute to associations between cannabis use and altered cerebellar-cortical rsFC, rather than unique causal impacts of cannabis use on cerebellar-cortical rsFC.

The thalamocortical inhibitory network controls human conscious perception.

Although conscious perception is a fundamental cognitive function, its neural correlates remain unclear. It remains debatable whether thalamocortical interactions play a decisive role in conscious perception. To clarify this, we used functional magnetic resonance imaging (fMRI) where flickering red and green visual cues could be perceived either as a non-fused colour or fused colour. Here we show significantly differentiated fMRI neurodynamics only in higher-order thalamocortical regions, compared with first-order thalamocortical regions. Anticorrelated neurodynamic behaviours were observed between the visual stream network and default-mode network. Its dynamic causal modelling consistently provided compelling evidence for the involvement of higher-order thalamocortical iterative integration during conscious perception of fused colour, while inhibitory control was revealed during the non-fusion condition. Taken together with our recent magnetoencephalography study, our fMRI findings corroborate a thalamocortical inhibitory model for consciousness, where both thalamic inhibitory regulation and integrative signal iterations across higher-order thalamocortical regions are essential for conscious perception.

In-Home Monitoring Technology for Aging in Place: Scoping Review.

BACKGROUND: For successful aging-in-place strategy development, in-home monitoring technology is necessary as a new home modification strategy. Monitoring an older adult's daily physical activity at home can positively impact their health and well-being by providing valuable information about functional, cognitive, and social health status. However, it is questionable how these in-home monitoring technologies have changed the traditional residential environment. A comprehensive review of existing research findings should be utilized to characterize recent relative technologies and to inform design considerations. OBJECTIVE: The main purpose of this study was to classify recent smart home technologies that monitor older adults' health and to architecturally describe these technologies as they are used in older adults' homes. METHODS: The scoping review method was employed to identify key characteristics of in-home monitoring technologies for older adults. In June 2021, four databases, including Web of Science, IEEE Xplore, ACM Digital Library, and Scopus, were searched for peer-reviewed articles pertaining to smart home technologies used to monitor older adults' health in their homes. We used two search strings to retrieve articles: types of technology and types of users. For the title, abstract, and full-text screening, the inclusion criteria were original and peer-reviewed research written in English, and research on monitoring, detecting, recognizing, analyzing, or tracking human physical, emotional, and social behavior. The exclusion criteria included theoretical, conceptual, or review papers; studies on wearable systems; and qualitative research. RESULTS: This scoping review identified 30 studies published between June 2016 and 2021 providing overviews of in-home monitoring technologies, including (1) features of smart home technologies and (2) sensor locations and sensor data. First, we found six functions of in-home monitoring technology among the reviewed papers: daily activities, abnormal behaviors, cognitive impairment, falls, indoor person positioning, and sleep quality. Most of the research (n=27 articles) focused on functional monitoring and analysis, such as activities of daily living, instrumental activities of daily living, or falls among older adults; a few studies (n=3) covered social interaction monitoring. Second, this scoping review also found 16 types of sensor technologies. The most common data types encountered were passive infrared motion sensors (n=21) and contact sensors (n=19), which were used to monitor human behaviors such as bodily presence and time spent on activities. Specific locations for each sensor were also identified. CONCLUSIONS: This wide-ranging synthesis demonstrates that in-home monitoring technologies within older adults' homes play an essential role in aging in place, in that the technology monitors older adults' daily activities and identifies various health-related issues. This research provides a key summarization of in-home monitoring technologies that can be applied in senior housing for successful aging in place. These findings will be significant when developing home modification strategies or new senior housing.

Cerebellar Structure and Function in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by early-onset repetitive behaviors, restricted interests, sensory and motor difficulties, and impaired social interactions. Converging evidence from neuroimaging, lesion and postmortem studies, and rodent models suggests cerebellar involvement in ASD and points to promising targets for therapeutic interventions for the disorder. This review elucidates understanding of cerebellar mechanisms in ASD by integrating and contextualizing recent structural and functional cerebellar research.

Examining Older Adults' Home Functioning Using the American Housing Survey.

Identifying individuals at risk of experiencing functional difficulty at home would support timely home safety assessment and modification services, which could lead to reducing home incidents such as falls. The objective of this study was to calculate older adults' functional difficulty at home scores using the 12 physical function items in the American Housing Survey National and Metropolitan Data (AHS). Among the 28,474 older adults selected for this study, we used 19,932 for measurement model development and 8542 for model testing. Confirmatory factor analysis confirmed an adequate fit of the one-dimensional model with all AHS 12 items loading on one latent construct (functional difficulty at home) (RMSEA: 0.034, CFI: 0.990, and TLI: 0.988). Based on our model selection process, we determined that the Graded Response Model was an optimal model for our analysis and separated two detected differential functioning items for each sex. Using the testing dataset, we validated that the estimated functional difficulty scores showed an expected item hierarchy and statistically significant differences in their association with housing and demographic conditions (p < 0.001). Our results demonstrated the process of using the 12 AHS physical function at home items to produce validated scores of older adults' functional difficulty at home.

Acute Liver Failure Secondary to Hepatic Infiltration of Malignant Melanoma.

Acute liver failure due to malignant melanoma is uncommon. We presents a case of acute liver failure secondary to hepatic infiltration of a malignant melanoma. An 86-year-old man was admitted with elevated liver enzymes and an increased lactate dehydrogenase level. His condition progressed to acute liver failure, but the etiology of liver failure was unclear. Esophagogastroduodenoscopy was performed to evaluate dyspepsia, which showed signs indicative of malignant melanoma. Based on the endoscopy findings and elevated liver enzyme levels, liver biopsy was performed to confirm the presence of malignant melanoma. Hepatic infiltration of malignant melanoma was observed histologically. However, massive and diffuse liver metastasis is very rare and difficult to identify on imaging studies. If the etiology of liver failure is unclear, diffuse metastatic melanoma infiltration should be considered as differential diagnosis. Early liver biopsy can help to clarify the diagnosis.

Glucose deprivation enhances resistance to paclitaxel via ELAVL2/4-mediated modification of glycolysis in ovarian cancer cells.

The dysregulation of glycolysis regardless of oxygen availability is one of the major characteristics of cancer cells. While the drug resistance of ovarian cancer cells has been extensively studied, the molecular mechanism of anticancer drug resistance under low-glucose conditions remains unknown. In this study, we investigated the pathway mediating drug resistance under low-glucose conditions by examining the relationship between embryonic lethal abnormal vision Drosophila homolog-like (ELAVL) protein and glycolysis-related enzymes. Ovarian cancer cells resistant to 2.5 nM paclitaxel were exposed to low-glucose media for 2 weeks, and the expression levels of ELAVL2, ELAVL4, glycolytic enzymes, and drug resistance-related proteins were elevated to levels comparable to those in cells resistant to 100 nM paclitaxel. Gene silencing of ELAVL2/4 using small interfering RNA prevented the upregulation of glycolysis-related enzymes, reduced lactate production, and sensitized 2.5 nM paclitaxel-resistant ovarian cancer cells to anticancer agents under hypoglycemic conditions. Furthermore, pharmacological inhibition of glycolytic enzymes with 2-deoxyglucose, a specific inhibitor of glycolysis, triggered caspase-dependent apoptosis, reduced lactate generation, and blocked the expression of drug resistance-related proteins under low-glucose conditions. These results suggest that the level of ELAVL2/4 is responsible for the development of chemoresistance through activation of the glycolysis pathway under glucose deprivation conditions.

Cerebellar Activation Deficits in Schizophrenia During an Eyeblink Conditioning Task.

The cognitive dysmetria theory of psychotic disorders posits that cerebellar circuit abnormalities give rise to difficulties coordinating motor and cognitive functions. However, brain activation during cerebellar-mediated tasks is understudied in schizophrenia. Accordingly, this study examined whether individuals with schizophrenia have diminished neural activation compared to controls in key regions of the delay eyeblink conditioning (dEBC) cerebellar circuit (eg, lobule VI) and cerebellar regions associated with cognition (eg, Crus I). Participants with schizophrenia-spectrum disorders (n = 31) and healthy controls (n = 43) underwent dEBC during functional magnetic resonance imaging (fMRI). Images were normalized using the Spatially Unbiased Infratentorial Template (SUIT) of the cerebellum and brainstem. Activation contrasts of interest were "early" and "late" stages of paired tone and air puff trials minus unpaired trials. Preliminary whole brain analyses were conducted, followed by cerebellar-specific SUIT and region of interest (ROI) analyses of lobule VI and Crus I. Correlation analyses were conducted between cerebellar activation, neuropsychological test scores, and psychotic symptom scores. In controls, the largest clusters of cerebellar activation peaked in lobule VI during early dEBC and Crus I during late dEBC. The schizophrenia group showed robust cortical activation to unpaired trials but no significant conditioning-related cerebellar activation. Crus I ROI activation during late dEBC was greater in the control than schizophrenia group. Greater Crus I activation correlated with higher working memory scores in the full sample and lower positive psychotic symptom severity in schizophrenia. Findings indicate functional cerebellar abnormalities in schizophrenia which relate to psychotic symptoms, lending direct support to the cognitive dysmetria framework.

Altered cerebellar-cortical resting-state functional connectivity in cannabis users.

BACKGROUND: Cannabis use has been associated with abnormalities in cerebellar mediated motor and non-motor (i.e. cognition and personality) phenomena. Since the cerebellum is a region with high cannabinoid type 1 receptor density, these impairments may reflect alterations of signaling between the cerebellum and other brain regions. AIMS: We hypothesized that cerebellar-cortical resting-state functional connectivity (rsFC) would be altered in cannabis users, relative to their non-using peers. It was also hypothesized that differences in rsFC would be associated with cannabis use features, such as age of initiation and lifetime use. METHODS: Cerebellar-cortical and subcortical rsFCs were computed between 28 cerebellar lobules, defined by a spatially unbiased atlas template of the cerebellum, and individual voxels in the cerebral regions, in 41 regular cannabis users (20 female) and healthy non-using peers (N = 31; 18 female). We also investigated associations between rsFC and cannabis use features (e.g. lifetime cannabis use and age of initiation). RESULTS: Cannabis users demonstrated hyperconnectivity between the anterior cerebellar regions (i.e. lobule I-IV) with the posterior cingulate cortex, and hypoconnectivity between the rest of the cerebellum (i.e. Crus I and II, lobule VIIb, VIIIa, VIIIb, IX, and X) and the cortex. No associations were observed between features of cannabis use and rsFC. CONCLUSIONS: Cannabis use was associated with altered patterns of rsFC from the cerebellum to the cerebral cortex which may have a downstream impact on behavior and cognition.

TrkB/C-induced HOXC6 activation enhances the ADAM8-mediated metastasis of chemoresistant colon cancer cells.

The abnormal expression of tropomyosin receptor kinase (Trk) serves an important role in the promotion of cancer progression. Homeobox C6 (HOXC6) and A disintegrin and metalloproteinase domain­containing 8 (ADAM8) are associated with the invasiveness of cancer cells. However, the exact relationship between these molecules and their downstream signaling pathways in chemoresistant colon cancer cells are largely unknown. Therefore, the current study investigated the association between TrkB/C with HOXC6 and ADAM8 in the induction of drug­resistant colon cancer cell metastasis. The results demonstrated that chemoresistant colon cancer cells exhibited upregulated TrkB/C, HOXC6 and ADAM8 expression. Additionally, but also chemoresistant colon cancer cells demonstrated higher migratory activities compared with parent colon cancer cells. The pharmacological inhibition of TrkB/C activity reduced the phosphorylation of mitogen­activated protein kinase kinase/ERK and subsequently suppressed HOXC6 and ADAM8 expression. In addition, gene silencing of HOXC6 inhibited ADAM8 and MMP activity, and inhibited the migration and invasion of drug­resistant cancer cells. However, the targeted downregulation of ADAM8 using small interfering RNA failed to suppress TrkB/C­associated ERK­mediated HOXC6 signaling activity. Furthermore, pre­treatment with ADAM10­ and ADAM17­specific inhibitors had no effect on attenuating the invasiveness of chemoresistant colon cancer cells. The results indicated that TrkB/C­mediated ERK activation serves an important role in the metastasis of drug­resistant colon cancer cells through the regulation of HOXC6/ADAM8 activity.

Understanding Older Adults' Perception and Usage of Indoor Lighting in Independent Senior Living.

The main purpose of this research is to examine the lighting condition and residents' perception of lighting in a senior retirement community in order to understand various environmental issues related to lighting. Also, this research aims to suggest a new lighting solution to compensate for older adults' vision impairment and challenges at home for a successful aging place. In the normal aging process, more than 30% of older adults have a vision impairment, which negatively affects health and well-being of older adults such as limited activities, falling, loneliness, depression, anxiety, and a sense of control. Via a mixed method study design, residents in senior living communities were asked to describe the adequacy of light levels and specific tasks and needs related to lighting at their home. In addition to the survey and interview, indoor lighting assessments were conducted during the in-home session. The research findings highlighted older adults' experience and perception of lighting in their homes. Paired-sample t test indicated that there were statistically significant differences in light levels between normal conditions and full capacity conditions in all spaces. In order to address various challenges which older adults have been experiencing in their home for a long time, this research suggests new smart lighting platform which provides a proper level of illumination in older adult's homes. Such a smart platform is proactive and can dynamically adjust the smart devices or lighting fixtures in situ, while older adults are performing certain tasks.

Difficult Biliary Cannulation from the Perspective of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: Identifying the Optimal Timing for the Rescue Cannulation Technique.

Background/Aims: Recently, the European Society of Gastrointestinal Endoscopy (ESGE) proposed criteria for "difficult biliary cannulation" during endoscopic retrograde cholangiopancreatography (ERCP). This study aimed to investigate the clinical relevance of the ESGE criteria from the perspective of post-ERCP pancreatitis (PEP). Methods: An ERCP database was prospectively maintained between November 2014 and December 2015 across six teaching hospitals in South Korea. The ESGE criteria (biliary cannulation time, the number of cannulation attempts, and inadvertent pancreatic duct [PD] manipulation) were recorded in this database as well as other technical factors. Logistic regression analysis was used to identify risk factors for PEP. Then, the PEP prediction model was investigated using decision tree analysis. Results: We analyzed 1,067 consecutive patients with naïve papilla. The overall rate of PEP was 6.6%. Multivariate analysis revealed that female sex (odds ratio [OR], 1.860; 95% confidence interval [CI], 1.124 to 3.078), a selective biliary cannulation duration >5 minutes (OR, 3.282; 95% CI, 1.641 to 6.566), and inadvertent PD manipulation (OR, 2.614; 95% CI, 1.480 to 4.617) were significant factors affecting PEP. Decision tree analysis revealed that biliary cannulation time (χ2=49.857, p<0.001) and inadvertent PD manipulation (χ2=8.556, p=0.010) were decisive factors. PEP occurred in 3.9%, 11.8%, and 16.2% of patients with biliary cannulation duration lasting 3 to 5 minutes, >5 minutes, and >5 minutes with inadvertent PD manipulation, respectively. Conclusions: Biliary cannulation time and inadvertent PD manipulation could be relevant indicators of PEP, and 5 minutes might be used as a cutoff value for the implementation of the rescue cannulation technique.

Preparation, characterization, and pharmacological study of a novel long-acting FGF21 with a potential therapeutic effect in obesity.

FGF21 (Fibroblast Growth Factor 21), which is expressed in the liver, adipose tissue, and pancreas, has been widely known as a therapeutic candidate for metabolic diseases. Though FGF21 is crucial to glucose, lipid, and energy homeostasis, it is not straightforward to develop a new drug with FGF21 due to its short half-life in serum. Here, we derived a novel long-acting FGF21 (LAPS-FGF21), which is chemically conjugated to the human IgG4 Fc fragment for longer half-life in serum. The recombinant human IgG4 Fc fragment and FGF21 were prepared by the refolding of inclusion body and periplasmic expression in Escherichia coli overexpression systems, respectively. The efficacy study of LAPS-FGF21 in a Diet-Induced Obesity (DIO) mouse model revealed that LAPS-FGF21 reduced body weight effectively accompanied by improved glucose tolerance in a dose-dependent manner. The administration of LAPS-FGF21 also improved the blood profiles with a significant reduction in cholesterol and triglyceride levels. Additionally, the pharmacokinetic (PK) studies of LAPS-FGF21 using normal ICR mice demonstrated that the half-life of LAPS-FGF21 was approximately 64-fold longer than FGF21. Taken together, the LAPS-FGF21 could be a feasible drug candidate with excellent bodyweight loss efficacy and longer dosing interval by half-life increase in serum.