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Digital intervention tools against problematic smartphone usage help users control their consumption on smartphones, for example, by setting a time limit on an app. However, today's social media apps offer a mix of quasiessential and addictive features in an app (e.g., Instagram has following feeds, recommended feeds, stories, and direct messaging features), which makes it hard to apply a uniform logic for all uses of an app without a nuanced understanding of feature-level usage behaviors. We study when and why people regret using different features of social media apps on smartphones. We examine regretful feature uses in four smartphone social media apps (Facebook, Instagram, YouTube, and KakaoTalk) by utilizing feature usage logs, ESM surveys on regretful use collected for a week, and retrospective interviews from 29 Android users. In determining whether a feature use is regretful, users considered different types of rewards they obtained from using a certain feature (i.e., social, informational, personal interests, and entertainment) as well as alternative rewards they could have gained had they not used the smartphone (e.g., productivity). Depending on the types of rewards and the way rewards are presented to users, probabilities to regret vary across features of the same app. We highlight three patterns of features with different characteristics that lead to regretful use. First, "following"-based features (e.g., Facebook's News Feed and Instagram's Following Posts and Stories) induce habitual checking and quickly deplete rewards from app use. Second, recommendation-based features situated close to actively used features (e.g., Instagram's Suggested Posts adjacent to Search) cause habitual feature tour and sidetracking from the original intention of app use. Third, recommendation-based features with bite-sized contents (e.g., Facebook's Watch Videos) induce using "just a bit more," making people fall into prolonged use. We discuss implications of our findings for how social media apps and intervention tools can be designed to reduce regretful use and how feature-level usage information can strengthen self-reflection and behavior changes.

Amphibian biodiversity is declining globally, with over 40% of species being considered threatened to become extinct. Crucial to the success of conservation initiatives are a comprehensive understanding of life history and reproductive ecology of target species. Here we provide an overview of the Pseudacris genus, including breeding behaviour, reproduction, development, survival and longevity. We present an updated distribution map of the 18 species found throughout North America. We also summarize the conservation status at the national and subnational (state, provincial, and territorial) levels, in Canada, USA, and Mexico, to evaluate the relationship between life history traits and extinction risk. Results show a high degree of consistency in the life history traits of Pseudacris species considering their relative diversity and wide distribution in North America. However, data are lacking for several species, particularly in the Fat Frog and West Coast clades, causing some uncertainties and discrepancies in the literature. We also found that the most threatened populations of chorus frog were located in the east coast of the USA, potentially as a result of increased levels of anthropogenic disturbance. We suggest that the similarities in life history traits among chorus frog species provides an opportunity for collaboration and united efforts for the conservation of the genus. Supplementary Information The online version contains supplementary material available at 10.1186/s12983-021-00425-w.

Various cucurbitacins have been isolated, and their structures have been elucidated. Owing to their economic potential and importance as active pharmacological compounds, their cytotoxicity in various cancer cells has been assessed. Here, we mined several candidate genes with potential involvement in cucurbitacin biosynthesis in watermelon (Citrullus lanatus) and performed in vitro enzymatic assays and instrumental analyses using various substrates to identify cucurbitacin functions and products. Enzymatic activities of two acetyltransferases (ACTs) and one UDP-glucosyltransferase (UGT) against cucurbitacins were confirmed, resulting in the synthesis of novel cucurbitacins in vivo and/or in vitro to our knowledge. As ACTs and UGT are involved in the dynamic conversion of cucurbitacins by catalyzing acetylation and glucosylation at moieties in the cucurbitacins skeleton, these findings improve our knowledge on how these genes contribute to the diversity of cucurbitacins., Kim et al. use RNAseq of two watermelons to select candidate genes coding for enzymes that catalyze modifications of cucurbitacins. They characterise four of the 16 candidate enzymes (3 different acetyltransferases and one UDP-glucosyltransferase) by HPLC, LC-MS, NMR, and in vitro enzymatic assay. They further show with in vivo assay in Drosophila, that acetylation of cucurbitacin increases neuronal activity in insects.

International audience; Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disorder which affects small-and, to a lesser degree, medium-sized vessels. ANCA-associated vasculitis encompasses three disease phenotypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). This classification is largely based on clinical presentations and has several limitations. Recent research provided evidence that genetic background, risk of relapse, prognosis, and co-morbidities are more closely related to the ANCA serotype, proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, compared to the disease phenotypes GPA or MPA. This finding has been extended to the investigation of biomarkers predicting disease activity, which again more closely relate to the ANCA serotype. Discoveries related to the immunopathogenesis translated into clinical practice as targeted therapies are on the rise. This review will summarize the current understanding of the immunopathogenesis of ANCA-associated vasculitis and the interplay between ANCA serotype and proposed disease biomarkers and illustrate how the extending knowledge of the immunopathogenesis will likely translate into development of a personalized medicine approach in the management of ANCA-associated vasculitis.

Introduction: While intensive induction chemotherapy has been standard-or-care for patients with acute myeloid leukemia (AML), intensive regimens have often been limited in elderly patients with comorbidities. As an alternative option, less intensive hypomethylating agents (HMAs), decitabine (DAC) and azacitidine (AZA), are currently being used in these unfit patients. However, their low response rates and adverse events when administered alone suggest a need to develop novel HMAs that elicit enhanced efficacy and reduced mortality. A recent study demonstrated pharmacological improvements of a novel 4′-thio-modified analog, 5-aza-4′-thio-2′-deoxycytidine (hereafter NTX-301), including enhanced chemical stability and incorporation into DNA and improved preclinical efficacy (Thottassery, 2014). However, the mechanism of action (MoA) of NTX-301 has not yet been understood. Herein, we aim to thoroughly investigate the preclinical efficacy and MoAs of NTX-301 in AML through comparative analysis with DAC and AZA. To this end, we used in vitro and in vivo preclinical models of AML and performed multiomics-based analyses. Results: We comprehensively examined viability of 200 cancer cell lines (CCLs) upon treatment with NTX-301. Consistent with the current use of HMAs as therapeutics for hematologic malignancies, this sensitivity profiling displayed the most remarkable potency of NTX-301 toward blood CCLs (OR=3.97, p=0.0003). In addition, phenotypic assays revealed that the anti-leukemic activity of NTX-301 was superior to that of DAC, which is attributed to more effective actions in inducing apoptosis, cell cycle arrest, and differentiation. Supporting the in vitro results, orally administrated NTX-301 led to more potent tumor regression, better tolerability, and survival benefits over DAC and AZA in both systemic (1.5-2.0 mg/kg, qdx5 then 2 days off, 5 days on, and 9 days off, for 3 cycles) and subcutaneous (0.2-1.5 mg/kg) xenograft models. To assess the underlying MoAs, we interrogated global alterations at the transcriptome and methylome levels upon treatment with NTX-301 in three AML cell lines using RNA sequencing and methylation array. Methylome analyses revealed that NTX-301-induced demethylation patterns were distinguished from DAC; DAC triggered stronger global demethylation than NTX-301 did, whereas NTX-301 derived rather selective demethylation, preferentially in early-replicating regions, H3K27ac-marked regions, and non-CpG islands. In transcriptome analyses compared with DAC, NTX-301 more markedly elicited a transcriptional reversal toward a normal myeloid-like signature by increasing a differentiation signature and suppressing a leukemic stem cell signature. NTX-301 also mediated more pronounced activation of DNA damage response and the p53 pathway, which are characterized by marked induction of pH2AX and pChk1 and increased stability of p53, respectively. Given the synthetic lethality of p53 activation and BCL2 inhibition (Rongqing, 2017), stronger p53 stabilization by NTX-301 may confer more benefits in combination with venetoclax. Indeed, the combination of NTX-301 + venetoclax produced a more synergistic combination index compared with DAC + venetoclax. Strikingly, the combined NTX-301 (0.5-2.0 mg/kg) + venetoclax (50 mg/kg) achieved complete tumor remission, no notable toxicity, and prolonged survival benefits over AZA (2.5 mg/kg) + venetoclax (50 mg/kg) in preclinical models of AML. By integrating sensitivity profiles and multiomics data of 200 CCLs, we interrogated molecular determinants associated with sensitivity to NTX-301. Intriguingly, when comparing methylomes between sensitive and resistant CCLs, we found a significantly biased global hypermethylation trend toward sensitive CCLs. A combinatorial set of the most significantly biased 352 differentially methylated regions (FDR Conclusions: Our study demonstrated an improved therapeutic index of NTX-301 over traditional HMAs, providing a rationale for further clinical development of the agent as a single-agent or in combination with other agents. We also believe that our study for MoAs and biomarkers will improve our understanding of NTX-301. Disclosures Lim: Pinotbio: Research Funding. Yoo: Pinotbio: Research Funding. Cho: Pinotbio: Research Funding. Choi: Pinotbio: Research Funding. Jung: Pinotbio: Research Funding. Jung: Pinotbio: Current Employment. Lee: Pinotbio: Current Employment. Chun: Pinotbio: Current Employment. Go: Pinotbio: Current Employment. Lee: Pinotbio: Current Employment. Choi: Pinotbio: Research Funding.

Machine vision systems are being utilized extensively in agriculture applications. Daytime imaging in outdoor field conditions presents challenges such as variable lighting and colour inconsistencies due to sunlight. Motion blur can occur due to vehicle movement and vibrations from ground terrain. A camera system with active lighting can be a solution to overcome these challenges. In this study, the usage of over-current driven LEDs to produce a powerful flash was investigated as a viable light source for daytime imaging. The current drawn by an LED was increased by a factor of six times its normal rating resulting in increased illuminance. A circuit was designed for storing and releasing energy to the LEDs for a strobe-like effect and a controller was used for synchronizing the strobe with a camera to acquire images. The system was deployed in an apple orchard on three days in summer of 2020. Images were taken throughout the day in both sunny and cloudy conditions of different canopy structures. There was substantial improvement in image brightness and colour consistency by using the LED flashes. Images captured by the prototype system during an 11-hour period showed an average decrease of 85% in standard deviation for the Hue-Saturation-Value (HSV) channels compared to that of the auto-exposure setting. Additionally, the prototype system was able to fix motion blur in images averaging 7 mm in error for a stereo vision application with the camera moving at 7 km/hr. These results show that the designed LED flash system can reduce the undesirable effects of lighting variability and motion blur in images stemming from outdoor field conditions.

BACKGROUND/OBJECTIVES This study analyzed the quality of lunches provided in senior leisure service (SLS) facilities and compared institutional foodservice (IF) and non-institutional foodservice (non-IF). SUBJECTS/METHODS Data of 390 adults aged 65 years or older who ate lunches in SLS facilities were analyzed using the information from the 2013–2017 Korea National Health and Nutrition Examination Survey. The participants were classified into IF (n = 129) and non-IF (n = 261) groups according to meal type provided. The intake of major food groups, energy and nutrients, and nutrient adequacy ratio (NAR) and mean adequacy ratio (MAR) were analyzed. The diversity of meals was evaluated by food group patterns, dietary diversity score (DDS) and dietary variety score (DVS). Energy intake was adjusted in model 1, while energy and sex were adjusted in model 2. All confounding variables were adjusted in model 3. RESULTS The intake of seafoods (P < 0.001 in models 1, 2, and 3), seaweeds (P < 0.01 in models 1 and 2), and dairy products (P < 0.05 in models 1, 2, and 3) was significantly higher in the IF group. No significant difference existed in energy intake; however, the intake of all nutrients except carbohydrate and vitamin C was significantly higher in the IF group. NAR of all nutrients, excluding vitamin C, was higher in the IF group, and MAR was also higher in the IF group (P < 0.001 in models 1, 2, and 3). The IF group had significantly higher DDS and DVS than the non-IF group (P < 0.001). CONCLUSIONS The lunches provided in SLS facilities were better in terms of quantity and quality when provided through IF than through non-IF. More systematic foodservice programs should be implemented in SLS facilities, especially in facilities wherein users prepare their own meals.

BACKGROUND The colitis-associated cancer exhibits different characteristics according to sex in the initiation and progression of the tumors. The aim of this study was to investigate the sex-associated difference in the azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated cancer model. METHODS The AOM/DSS ICR mouse model was established to compare male with female, and then the severity of colitis-associated carcinogenesis was examined macroscopically and histologically regarding the number, size, and location of tumors. Subsequently, levels of colonic mucosal cytokine, interleukin (IL)-1β and myeloperoxidase (MPO) were assessed. RESULTS At the 16th week, the tumor multiplicity and the pro-inflammatory factors differed according to sex. The total tumor number was significantly higher in male (P = 0.020) and the number of large tumors (diameter > 2 mm) was higher in male (P = 0.026). In male, the tumors located more in distal colon (P = 0.001). MPO was significantly higher in AOM/DSS-treated male mice compared to the control group (P = 0.003), whereas the corresponding female group showed no significant change (P = 0.086). Colonic IL-1β level significantly increased in AOM/DSS groups compared to control groups both in male and female (male, P = 0.014; female, P = 0.005). It was higher in male group; however, there was no statistical significance (P = 0.226). CONCLUSIONS In AOM/DSS murine model, colitis-associated colon tumorigenesis are induced more severely in male mice than female probably by way of inflammatory mediators such as IL-1β and MPO. The sex-related differences at the animal model of colon cancer suggest the importance of approach to disease with sex-specific medicine in human.

BACKGROUND The aim of this study was to investigate the effect of N-methyl-N-nitrosourea (MNU) treatment followed by chronic Helicobacter pylori SS1 and H. felis colonization on the stomachs of C57BL/6 mice. The role of MNU and Helicobacter species in gastric carcinogenesis was also elucidated. METHODS A total of 69 C57BL/6 mice at 4 weeks of age were divided into 6 groups according to MNU treatment and H. pylori SS1 or H. felis infection. The mice were sacrificed at 21 and 50 weeks. The degree of inflammation was determined by histopathology. The levels of gastric mucosal myeloperoxidase, TNF-α, and interleukin-1β (IL-1β) were measured by ELISA. RESULTS In the H. felis groups with or without MNU, the incidence of gastric tumors was 21.1% and 35.0% at 21 and 50 weeks, respectively. No gastric tumors were observed in all control mice. At 50 weeks, 37.5% of gastric adenoma cases were observed in the H. felis alone and MNU + H. felis groups. Furthermore, 12.5% of gastric adenocarcinoma cases were observed in the MNU alone and MNU + H. felis groups. The gastric mucosal IL-1β level was significantly higher in the MNU + H. felis group at 21 weeks and H. felis group at 50 weeks, respectively, than that for control mice (P < 0.05). However, the effect of MNU on H. pylori SS1-induced gastric carcinogenesis was low compared to that on H. felis. CONCLUSIONS Administration of MNU before H. felis infection provokes severe inflammation through IL-1β, and eventually induces gastric cancer. However, the role of MNU in H. pylori SS1-induced gastric carcinogenesis model is minor.

Robotic pruning is a potential solution to address the issues of labor shortages and high associated costs, but it has challenges due to the unstructured working environment. For successful robotic pruning, target branches have to be reached with fewer spatial requirements for the end-effector cutter and the manipulator. A three-rotational (3R) degrees of freedom (DoF) end-effector was designed considering maneuvering, spatial, mechanical, and horticultural requirements. Simulations were conducted with the end-effector to investigate the reachable workspace, the cutter frame orientation, and the manipulability index. The simulation results suggested that the proposed design has a spherical reachable workspace with a void due to the presence of a physical constraint of the linear arm. The manipulability index was determined to be independent of the rotation of the first and last joint of the end-effector. The prototype of the proposed end-effector was integrated with a cartesian manipulator. An Arduino-based control system was developed along utilizing a Matlab graphical user interface (GUI). A series of field tests were conducted on ‘Fuji’/Bud. 9 apple trees with trellis-trained architecture. The field tests validated the simulation results, and the end-effector successfully cut branches up to ~25 mm diameter at wide range of orientations. This study provides the foundation for future investigations of branch accessibility for pruning with an integrated 3R end-effector and a cartesian manipulator system following a collision free trajectory.

The colonic response to stress is greater in female rats than in male rats. The aim of this study was to evaluate the effect of probiotics in the repeated water avoidance stress (rWAS)-induced colonic microinflammation model of Wistar rats in a sex-specific manner. The three groups (no-stress, WAS, and WAS with probiotics) were exposed to r-WAS for 1 h daily for 10 days, and Lactobacillus farciminis was administered by oral gavage for 10 days to animals in the probiotics group. The visceromotor response (VMR) to colorectal distension (CRD) was assessed using a barostat and noninvasive manometry before and after WAS exposure. Immunohistochemistry for mast cells and real-time polymerase chain reaction (RT-PCR) for detection of mucosal cytokines were performed using distal colon tissue after the animals were sacrificed. Significant reduction of VMR to CRD (visceral analgesia) was observed at 60 mmHg in the female WAS group (P = 0.045), but not in males. In addition, the female WAS with probiotics group showed a significantly lower colonic mucosal mast cell count in comparison to the female WAS group (P = 0.013), but this phenomenon was not observed in the male group. The colonic mucosal mRNA levels of interferon-γ (IFNR), tumor necrosis factor-α (TNFA), interleukin (IL) 6, and IL17 were higher in the female WAS group than in the male WAS group. The mRNA levels of IFNR, TNFA, and IL6 were significantly decreased in WAS females who received probiotics (all P < 0.050). In conclusion, rWAS is induced in a sex-specific manner. A 10-day-long treatment with L. farciminis is an effective therapy for rWAS-induced colonic microinflammation in female rates, but not in male rats.

Background The aim of this study was to investigate the effect of N-methyl-N-nitrosourea (MNU) treatment followed by chronic Helicobacter pylori SS1 and H. felis colonization on the stomachs of C57BL/6 mice. The role of MNU and Helicobacter species in gastric carcinogenesis was also elucidated. Methods A total of 69 C57BL/6 mice at 4 weeks of age were divided into 6 groups according to MNU treatment and H. pylori SS1 or H. felis infection. The mice were sacrificed at 21 and 50 weeks. The degree of inflammation was determined by histopathology. The levels of gastric mucosal myeloperoxidase, TNF-α, and interleukin-1β (IL-1β) were measured by ELISA. Results In the H. felis groups with or without MNU, the incidence of gastric tumors was 21.1% and 35.0% at 21 and 50 weeks, respectively. No gastric tumors were observed in all control mice. At 50 weeks, 37.5% of gastric adenoma cases were observed in the H. felis alone and MNU + H. felis groups. Furthermore, 12.5% of gastric adenocarcinoma cases were observed in the MNU alone and MNU + H. felis groups. The gastric mucosal IL-1β level was significantly higher in the MNU + H. felis group at 21 weeks and H. felis group at 50 weeks, respectively, than that for control mice (P < 0.05). However, the effect of MNU on H. pylori SS1-induced gastric carcinogenesis was low compared to that on H. felis. Conclusions Administration of MNU before H. felis infection provokes severe inflammation through IL-1β, and eventually induces gastric cancer. However, the role of MNU in H. pylori SS1-induced gastric carcinogenesis model is minor.

본 연구는 경기도 소재 초등돌봄교실의 돌봄전담사를 대상으로 집단면담조사 및 설문조사를 실시하여 도시와 농촌의 급 · 간식관리 현황을 비교 분석하였으며, 그 결과를 요약하면 다음과 같다. 첫째, 돌봄전담사 7명을 대상으로 한 집단면담조사 결과, 관련 지침이나 전문가의 도움 없이 돌봄전담사가 급 · 간식 운영을 전담하고 있었으며, 예산 부족으로 인한 질적 저하가 문제점으로 나타났다. 또한 초등돌봄교실의 급 · 간식을 공동관리할 수 있는 전문기관의 필요성이 도출되었다. 둘째, 돌봄전담사 101명을 대상으로 한 설문조사 결과, 학기 중 간식비는 평균 1,463원, 방학 중 급식비는 평균 4,062원이었으며, 학기 중 간식비 (p = 0.015)와 방학 중 급식비 (p = 0.039)는 농촌이 도시보다 유의적으로 적었다. 학기 중, 방학 중 급 · 간식 모두 완제품을 구매해서 제공하는 학교가 가장 많았으며 도시와 농촌 간 차이는 없었다. 셋째, 급식 영양관리기준이 있는 학교는 10% 미만에 불과하였다. 급식식단을 별도로 작성하고 있는 학교는 101개교 중 47개교였으며, 이 중 30개교 (63.8%)는 도시락공급업체로부터 식단을 제공받고 있었고, 17개 (19.3%)에서는 돌봄전담사가 식단을 작성하고 있었다. 간식식단을 작성하는 학교는 80개교로, 이 중 45개교 (44.6%)에서는 돌봄전담사가 식단을 작성하고 있었다. 농촌은 도시에 비해 돌봄전담사가 급식식단을 작성하는 비율이 높은 경향이 있었다 (p = 0.054). 넷째, 위생관리 기준이 있는 학교는 101개교 중 34개교(33.7%)에 불과하였으며, 31개교는 급 · 간식 제공 전 검식을 하지 않고 있었고 정기적인 건강검진을 하지 않는 돌봄전담사도 56.4%에 달했다. 급 · 간식 위생관리 현황은 지역에 따른 차이가 나타나지 않았다. 다섯째, 돌봄전담사가 응답한 적정 1회 간식비는 1,924원으로 실제 간식비보다 높아 적정 간식비에 대한 검토가 필요해 보였다. 바람직한 급 · 간식의 운영형태에 대한 의견에서는 초등돌봄교실 전문 급 · 간식지원센터 설치가 바람직하다는 응답이 48개교로 가장 많았다. 본 연구결과, 초등돌봄교실의 급 · 간식 운영에서는 지역구분과 관계없이 식단관리 및 위생관리 등에서 문제점이 나타났다. 초등돌봄교실에 참여하는 어린이들에게 위생적이며 영양이 풍부한 급 · 간식을 제공하기 위해서는 돌봄전담사가 식단작성 등 관련 업무를 담당하고 있는 현실을 고려하여 현장에서 효율적으로 활용할 수 있는 구체적인 급 · 간식 운영지침 마련이 시급하며, 돌봄전담사를 대상으로 한 영양 · 위생 교육 프로그램 개발이 필요하다. 또한 초등돌봄교실 급 · 간식 권장패턴 및 참고식단 개발이 필요하며, 정부 차원의 효율적인 제도 마련과 지원이 요구된다. 특히 농촌은 도시에 비해 급 · 간식의 단가가 낮고 돌봄전담사가 식단을 작성하는 경우가 많아 급 · 간식 단가의 상승을 우선적으로 고려할 필요가 있으며, 체계적인 급 · 간식 관리를 위한 제도 도입이 선행되어야 할 것이다.