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Abstract Background Surgery is the primary treatment for non-small cell lung cancer (NSCLC), but microscopic residual disease may be unavoidable. Preclinical studies have shown that volatile anesthetics might suppress host immunity and promote a pro-malignant environment that supports cancer cell proliferation, migration, and angiogenesis, whereas propofol may preserve cell-mediated immunity and inhibit tumor angiogenesis. However, clinical evidence that propofol-based total intravenous anesthesia (TIVA) can reduce tumor recurrence after curative resection remains inconsistent due to the retrospective observational nature of previous studies. Therefore, we will test the hypothesis that the recurrence-free survival (RFS) after curative resection of NSCLC is higher in patients who received TIVA than volatile anesthetics (GAS) in this multicenter randomized trial. Methods This double-blind, randomized trial will enroll patients at 22 international sites, subject to study registration, institutional review board approval, and patient written informed consent. Eligible patients are adult patients undergoing lung resection surgery with curative intent for NSCLC. Exclusion criteria will be contraindications to study drugs, American Society of Anesthesiologists physical status IV or higher, or preexisting distant metastasis or malignant tumor in other organs. At each study site, enrolled subjects will be randomly allocated into the TIVA and GAS groups with a 1:1 ratio. This pragmatic trial does not standardize any aspect of patient care. However, potential confounders will be balanced between the study arms. The primary outcome will be RFS. Secondary outcomes will be overall survival and complications within postoperative 7 days. Enrollment of 5384 patients will provide 80% power to detect a 3% treatment effect (hazard ratio of 0.83) at alpha 0.05 for RFS at 3 years. Discussion Confirmation of the study hypothesis would demonstrate that a relatively minor and low-cost alteration in anesthetic management has the potential to reduce cancer recurrence risk in NSCLC, an ultimately fatal complication. Rejection of the hypothesis would end the ongoing debate about the relationship between cancer recurrence and anesthetic management. Trial registration The study protocol was prospectively registered at the Clinical trials ( https://clinicaltrials.gov , NCT06330038, principal investigator: Hyun Joo Ahn; date of first public release: March 25, 2024) before the recruitment of the first participant.

Background Time-domain parameters are less reliable in children due to increased arterial and chest wall compliance. We assessed the ability of indices derived from frequency analysis of photoplethysmography (PPG) and arterial blood pressure (ABP) waveforms to predict the hemodynamic state in children undergoing congenital heart surgery. Methods We analyzed waveforms after cardiopulmonary bypass period in 76 children who underwent total repair of congenital heart disease. Amplitude density of baseline and amplitude modulation in PPG and ABP by respiratory frequency were obtained using fast Fourier transform analysis and normalized by cardiac pulse height (representing respiratory modulations in venous blood [PPG-DC%] and in amplitude [PPG-AC%] at respiratory frequency). The ratio of amplitude density of PPG at the cardiac frequency (CF) to ABP-CF was used to assess vascular compliance. We assessed volume replacement (ml/kg) and vasoactive inotropic score (VIS). Results Children requiring volume replacement > 10 ml/kg (15.8%) showed higher PPG-DC% than those not requiring it (median: 52.4%, 95% CI [24.8, 295.1] vs. 36.7% [10.7, 125.7], P = 0.017). In addition, children with a VIS > 7 (22.4%) showed higher PPG-CF/ABP-CF (3.6 [0.91, 10.8] vs. 1.2 [0.27, 5.5], P = 0.008). On receiver operating characteristic curve analysis, PPG-DC% predicted a higher fluid requirement (area under the curve: 0.71, 95% CI [0.604, 0.816], P = 0.009), while PPG-CF/ABP-CF predicted a higher VIS (0.714, [0.599, 0.812], P = 0.004). Conclusions Frequency domain analysis of PPG and ABP may assess hemodynamic status requiring fluid or vasoactive inotropic therapy after congenital heart surgery.

While numerous studies have confirmed a causal association between lipoprotein(a) [Lp(a)] and cardiovascular diseases, only a few studies have assessed the relationship between Lp(a) and pulmonary health, with inconsistent findings regarding this topic. This study’s aim was to examine whether levels of serum Lp(a) are associated with lung function in a dataset of relatively healthy older adults. We used longitudinal data collected at two time points 7.4 ± 1.5 years apart from 679 participants (52% women, 68 [65–71] years old) from the Berlin Aging Study II (BASE-II). Multiple linear regression models adjusting for covariates were applied to examine the association between Lp(a) and lung function. The forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC) were higher in both men and women with higher Lp(a) levels. However, since this association between lung function parameters and Lp(a) was not supported by Mendelian randomization analyses using recent genome-wide association study data, these relationships should be investigated in future work, as the observed differences are, in part, considerable and potentially clinically relevant.

Abstract Atopic dermatitis (AD) is an allergic, inflammatory skin disease caused by immune dysregulation. In this study, we investigated anti-atopic and anti-inflammatory activities of Sanguisorba hakusanensis ethanol extract (SHE) both in vivo using NC/Nga mice and in vitro using human HaCaT keratinocytes. Oral administration of SHE suppressed several atopic symptoms associated with house dust mites (induced with Dermatophagoides farinae extract) in NC/Nga mice and decreased serum levels of inflammatory mediators such as immunoglobulin E, histamine, and inflammatory chemokines. Additionally, SHE treatment reduced the infiltration of immune cells such as mast cells and macrophages in AD skin lesions. In vitro, interferon-γ- and tumor necrosis factor-α-stimulated HaCaT cells exhibited increased expression of T helper 1 and 2 chemokines; their expression was inhibited by SHE treatment. The anti-inflammatory effects of SHE treatment involved blocking of the mitogen-activated protein kinase and signal transducer and activator of transcription 1 signaling pathways. In conclusion, SHE exerts potent anti-atopic and anti-inflammatory effects and should be considered for the clinical treatment of AD.

Abstract Metal nanoclusters (NCs), an important class of nanoparticles (NPs), are extremely small in size and possess quasi-molecular properties. Due to accurate stoichiometry of constituent atoms and ligands, NCs have strong structure-property relationship. The synthesis of NCs is seemingly similar to that of NPs as both are formed by colloidal phase transitions. However, they are considerably different because of metal-ligand complexes in NC synthesis. Reactive ligands can convert metal salts to complexes, actual precursors to metal NCs. During the complex formation, various metal species occur, having different reactivity and fraction depending on synthetic conditions. It can alter their degree of participation in NC synthesis and the homogeneity of final products. Herein, we investigate the effects of complex formation on the entire NC synthesis. By controlling the fraction of various Au species showing different reactivity, we find that the extent of complex formation alters reduction kinetics and the uniformity of Au NCs. We demonstrate that this concept can be universally applied to synthesize Ag, Pt, Pd, and Rh NCs.

Abstract Particulate matter (PM), an environmental risk factor, is linked with health risks such as respiratory diseases. This study aimed to establish an animal model of PM-induced lung injury with artificial PM (APM) and identify the potential of APM for toxicological research. APM was generated from graphite at 600 °C and combined with ethylene. We analyzed diesel exhaust particulate (DEP) and APM compositions and compared toxicity and transcriptomic profiling in lungs according to the exposure. For the animal study, C57BL/6 male mice were intratracheally administered vehicle, DEP, or APM. DEP or APM increased relative lung weight, inflammatory cell numbers, and inflammatory protein levels compared with the vehicle control. Histological assessments showed an increase in particle-pigment alveolar macrophages and slight inflammation in the lungs of DEP and APM mice. In the only APM group, granulomatous inflammation, pulmonary fibrosis, and mucous hyperplasia were observed in the lungs of some individuals. This is the first study to compare pulmonary toxicity between DEP and APM in an animal model. Our results suggest that the APM-treated animal model may contribute to understanding the harmful effects of PM in toxicological studies showing that APM can induce various lung diseases according to different doses of APM.

Trunk compensatory movements frequently manifest during robotic-assisted arm reaching exercises for upper limb rehabilitation following a stroke, potentially impeding functional recovery. These aberrant movements are prevalent among stroke survivors and can hinder their progress in rehabilitation, making it crucial to address this issue. This study evaluated the efficacy of visual feedback, facilitated by an RGB-D camera, in reducing trunk compensation. In total, 17 able-bodied individuals and 18 stroke survivors performed reaching tasks under unrestricted trunk conditions and visual feedback conditions. In the visual feedback modalities, the target position was synchronized with trunk movement at ratios where the target moved at the same speed, double, and triple the trunk’s motion speed, providing real-time feedback to the participants. Notably, trunk compensatory movements were significantly diminished when the target moved at the same speed and double the trunk’s motion speed. Furthermore, these conditions exhibited an increase in the task completion time and perceived exertion among stroke survivors. This outcome suggests that visual feedback effectively heightened the task difficulty, thereby discouraging unnecessary trunk motion. The findings underscore the pivotal role of customized visual feedback in correcting aberrant upper limb movements among stroke survivors, potentially contributing to the advancement of robotic-assisted rehabilitation strategies. These insights advocate for the integration of visual feedback into rehabilitation exercises, highlighting its potential to foster more effective recovery pathways for post-stroke individuals by minimizing undesired compensatory motions.

AbstractIntroduction Various approaches are required to prevent and treat heterogeneity-based prostate cancer. Here, we analyzed the anticancer effects of metformin, which has a good toxicity profile and is inexpensive.Method From January 2010 to December 2019, analysis was conducted retrospectively in a cohort from the National Health Insurance Service database. The wash-out period was set for cancer diagnosis in 2010 and 2011, and subjects (105,279) diagnosed with prostate cancer (ICD C61) from 2012 to 2014 were excluded The final subjects (105,216) were defined as the metformin administration group when they took metformin for 180 days or more from January 2012 to December 2019. The non-metformin group was defined as those who took less than 180 days from January 2012 to December 2019. The prevalence of prostate cancer according to metformin administration and the risk according to the cumulative duration of metformin were analyzed.Results A total of 105,216 people were included in this study, with 59,844 in the metformin group and 45,372 in the metformin non-administration group. When calculating HRs (Hazard Rate) according to the cumulative period of metformin administration, metformin administration period length was inversely associated with prostate cancer risk (Q2 HR = 0.791 95% CI: 0.773–0.81, Q3 HR = 0.634 95% CI: 0.62–0.649, Q4 HR = 0.571 95% CI: 0.558–0.585). HRs tended to decrease with the cumulative duration of metformin administration.Conclusion This study confirmed that prostate cancer risk decreased with increasing duration of metformin administration. Metformin should be considered as a new strategy in the treatment and prevention of prostate cancer characterized by heterogeneity.

Trunk rehabilitation exercises such as those for remediating core stability can help improve the seated balance of patients with weakness or loss of proprioception caused by diseases such as stroke, and aid the recovery of other functions such as gait. However, there has not yet been any reported method for automatically determining the parameters that define exercise difficulty on a trunk rehabilitation robot (TRR) based on data such as the patient’s demographic information, balancing ability, and training sequence, etc. We have proposed a machine learning (ML)-based difficulty adjustment method to determine an appropriate virtual damping gain ${(}{D}_{\textit {virtual}}{)}$ of the controller for the TRR’s unstable training mode. Training data for the proposed system is obtained from 37 healthy young adults, and the trained ML model thus obtained is tested through experiments with a separate population of 25 healthy young adults. The leave-one-out cross validation results (37 subjects) from the training group for validation of the designed ML model showed 80.90% average accuracy (R2 score) for using the given information to predict the desired difficulty levels, which are represented by the level of balance performance quantified as Mean Velocity Displacement (MVD) of the center of pressure. Statistical analysis (Repeated measures analysis of variance) of subject performance also showed that ground truth difficulty levels from the training data and predicted difficulty levels did not differ significantly under any of the three exercise modes used in this study (Hard, Medium, and Easy), and the standard deviations were reduced by 16.39, 41.39, and 25.68%, respectively. Moreover, the Planar Deviation (PD) of the center of pressure, which was not the target parameter here, also showed results similar to the MVD, which indicates that the predicted ${D}_{\textit {virtual}}$ affected the difficulty level of balance performance. Therefore, the proposed ML model-based difficulty adjustment method has potential for use with people who have varied balancing abilities.

Abstract The aim of this study is to develop algorithms for automatic landmark extraction on women with various upper body types and body inclinations using the Grasshopper algorithm editor, which enables the user to interact with the 3D modeling interface. First, 15 landmarks were defined based on the morphological features of 3D body surfaces and clothing applications, from which automatic landmark extraction algorithms were developed. To verify the accuracy of the algorithms on various body shapes, this study determined criteria for key body shape factors (BMI, neck slope, upper body slope, and shoulder slope) that influence each landmark position, classified them into body shape groups and sorted the scan samples for each body type using the 6th SizeKorea database. The statistical differences between the scan-derived measurements and the SizeKorea measurements were compared, with an allowable tolerance of ISO 20685. In the case of landmarks with significant differences, the algorithm was modified. It was found that the algorithms were successfully applied to various upper body shapes, which improved the reliability and accuracy of the algorithm.

Abstract Three‐dimensional (3D) charge‐written periodic peak and valley nanoarray surfaces are fabricated on a (112¯0) ZnO single crystal grown via chemical vapor transport. Because the grown ZnO crystals exhibit uniform n‐type conduction, 3D periodic nanoarray patterns are formed via oxygen annealing. These periodically decorated structures show that the peak arrays are conducting at the nanoampere level, whereas the valley arrays are less conductive. Energy dispersive spectroscopy indicates that the valley arrays are deficient in zinc by ≈4–6 at%, and that the peak arrays are deficient in oxygen, respectively. Kelvin probe force microscopy reveals the presence of periodic wiggles featuring variations of ≈70–140‐meV between the peak and valley arrays. A significant decrease in the Fermi level of the valley region is observed (≈190 meV), which corresponds to a high zinc vacancy doping density of 2 × 1018 cm−3. This result indicates the periodic generation of an extremely large electric field (≈11 000 V cm−1) in the vicinity of the peak–valley arrays. Computational analysis corroborates the experimentally observed generation of VZn and the preferential formation of surface protrusions on ZnO (112¯0) rather than on (0001), based on surface effects, along with the generation of peak and valley features.

IntroductionAdipokines are proteins that are secreted by the adipose tissue. Although they are associated with obesity-related metabolic disorders, most studies have focused on adipokines expressed by visceral adipose tissue (VAT). This study aimed to identify the adipokine potentially derived from subcutaneous adipose tissue (SAT) and its clinical significance.MethodsSamples of SAT and VAT were obtained from six adult male patients who underwent laparoscopic surgery for benign gall bladder disease. Differentially expressed genes were analyzed by subjecting the samples to RNA sequencing. The serum concentration of selected proteins according to body mass index (BMI) was analyzed in 58 individuals.ResultsGDF10 showed significantly higher expression in the SAT, as per RNA sequencing (fold change = 5.8, adjusted P value = 0.009). Genes related to insulin response, glucose homeostasis, lipid homeostasis, and fatty acid metabolism were suppressed when GDF10 expression was high in SAT, as per genotype-tissue expression data. The serum GDF10 concentration was higher in participants with BMI ≥ 25 kg/m2 (n = 35, 2674 ± 441 pg/mL) than in those with BMI < 25 kg/m2 (n = 23, 2339 ± 639 pg/mL; P = 0.022). There was a positive correlation between BMI and serum GDF10 concentration (r = 0.308, P = 0.019).ConclusionsGDF10 expression was higher in SAT than in VAT. Serum GDF10 concentration was high in patients with obesity. Therefore, GDF10 could be a SAT-derived protein related to obesity.

BackgroundIndividuals with later bedtimes have an increased risk of difficulties with mood and substances. To investigate the causes and consequences of late bedtimes and other sleep patterns, researchers are exploring social media as a data source. Pioneering studies inferred sleep patterns directly from social media data. While innovative, these efforts are variously unscalable, context dependent, confined to specific sleep parameters, or rest on untested assumptions, and none of the reviewed studies apply to the popular Reddit platform or release software to the research community. ObjectiveThis study builds on this prior work. We estimate the bedtimes of Reddit users from the times tamps of their posts, test inference validity against survey data, and release our model as an R package (The R Foundation). MethodsWe included 159 sufficiently active Reddit users with known time zones and known, nonanomalous bedtimes, together with the time stamps of their 2.1 million posts. The model’s form was chosen by visualizing the aggregate distribution of the timing of users’ posts relative to their reported bedtimes. The chosen model represents a user’s frequency of Reddit posting by time of day, with a flat portion before bedtime and a quadratic depletion that begins near the user’s bedtime, with parameters fitted to the data. This model estimates the bedtimes of individual Reddit users from the time stamps of their posts. Model performance is assessed through k-fold cross-validation. We then apply the model to estimate the bedtimes of 51,372 sufficiently active, nonbot Reddit users with known time zones from the time stamps of their 140 million posts. ResultsThe Pearson correlation between expected and observed Reddit posting frequencies in our model was 0.997 on aggregate data. On average, posting starts declining 45 minutes before bedtime, reaches a nadir 4.75 hours after bedtime that is 87% lower than the daytime rate, and returns to baseline 10.25 hours after bedtime. The Pearson correlation between inferred and reported bedtimes for individual users was 0.61 (P

Currently, available medicine does not satisfy the clinical unmet needs of periodontal disease. Therefore, novel drugs with improved efficacy profiles are needed. We previously demonstrated that YH14642, water extracts of Notoginseng Radix and Rehmanniae Radix Preparata, improved probing depths in double-blind phase II clinical trial. However, it still has hurdles for commercialization due to the low efficiency of active compound extraction. To resolve this issue, we developed YH23537 through process optimization to extract active compounds efficiently while still achieving the chemical profile of YH14642. In this study, we investigated the therapeutic effects of YH23537 compared with YH14642 using a canine model of ligature-induced periodontitis. Human gingival fibroblast (hGF) cells were treated with various concentrations of YH23537 or YH14642 with lipopolysaccharide (LPS) for 24 hr. IL-6 and IL-8 levels in the conditioned media were determined using Luminex. Sixteen 3-year-old male beagle dogs had their teeth scaled and polished using a piezo-type ultrasonic scaler under general anesthesia and brushed once daily for the following 2 weeks. Two weeks after the scaling procedure, the left upper second premolar (PM2), third premolar (PM3), and fourth premolar (PM4) as well as the left lower PM3, PM4, and first molar (M1) were ligated with silk-wire twisted ligatures. The dogs were fed with soft moistened food to induce periodontitis for 8 weeks, and the ligatures were then removed. YH23537 and YH14642 were administered for 4 weeks, and clinical periodontal parameters such as plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BoP) were determined before and 1, 2, 3, and 4 weeks after treatment. YH23537 inhibited IL-6 and IL-8 secretion in a dose-dependent manner in hGF cells stimulated with LPS. The IC50 values for YH23537 were 43 and 54 μg/ml for IL-6 and IL-8, respectively, while the values for YH14642 were 104 and 117 μg/ml, respectively. In the animal study, clinical parameters including GI, PD, CAL, and BoP were significantly increased after 8 weeks of ligature-induced periodontitis. The YH23537 300 and YH23537 900 mg groups had significant improvements in CAL from 1 to 4 weeks after treatment in comparison to the placebo group. GR values in the YH23537 900 mg group were decreased throughout the treatment period. GI values were also reduced significantly after 4-week treatment with 300 and 900 mg of YH23537. YH23537 at 300 mg doses showed comparable efficacy for CAL and GR with 1,000 mg of YH14642. YH23537 showed therapeutic efficacy against periodontitis in dogs, mediated by anti-inflammatory effects. These findings indicate that YH23537 has the potential for further development as a new drug for patients suffering from periodontal disease.

A variety of isothiazolinone-containing small molecules have been registered and used as chemical additives in many household products. However, their biodistribution and potential harmful effects on human health, especially respiratory effects, were not yet identified in sufficient detail. The purpose of this study was to investigate whether a biocide comprising a mixture of chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) could reach the lungs and induce lung injury when exposure occurs by two administration routes involving the respiratory tract: intratracheal and intranasal instillation. To investigate the biodistribution of CMIT/MIT, we quantified the uptake of 14C-labeled CMIT/MIT in experimental animals for up to seven days after intratracheal and intranasal instillation. In the toxicity study, lung injury was assessed in mice using total inflammatory cell count in bronchoalveolar lavage fluid (BALF) and lung histopathology. The results of the biodistribution study indicated that CMIT/MIT were rapidly distributed throughout the respiratory tract. Using quantitative whole-body autoradiogram analysis, we confirmed that following intranasal exposure, CMIT/MIT reached the lungs via the respiratory tract (nose–trachea–lung). After 5 min post intratracheal and intranasal instillation, the amount of radiotracer ([14C]CMIT/MIT) in the lungs was 2720 ng g−1 and 752 ng g−1 tissue, respectively, and lung damage was observed. A higher amount of the radiotracer resulted in higher toxicity. Both intratracheal and intranasal instillation of CMIT/MIT increased inflammatory cell counts in the BALF and induced injuries in the alveoli. The frequency and the severity scores of injuries caused by intratracheal instillation were approximately-four to five times higher than those induced by intranasal instillation. Therefore, we concluded that CMIT/MIT could reach the lungs following nasal and intratracheal exposure and cause lung injuries, and the extent of injury was dependent on the exposure dose.

Purpose Deregulation of SNCA encoding α-synuclein (α-SYN) has been associated with both the familial and sporadic forms of Parkinson disease (PD). Epigenetic regulation plays a crucial role in PD. The intron1 of SNCA harbors a large unmethylated CpG island. Ten-eleven translocation methylcytosine dioxygenase 1 (TET1), a CpG island binding protein, can repress gene expression by occupying hypomethylated CpG-rich promoters, and therefore SNCA could be a target for TET1. We investigated whether TET1 binds to SNCA-intron1 and regulates gene expression. Methods The dopaminergic neuronal cell line, ReNcell VM, was used. Reverse transcription-polymerase chain reaction (RT-PCR), real time-quantitative PCR, Western blot, dot-blot, and Chromatin immunoprecipitation were conducted. The substantia nigra tissues of postmortem PD samples were used to confirm the level of TET1 expression. Results In the human dopaminergic cell line, ReNcell VM, overexpression of the DNA-binding domain of TET1 (TET1-CXXC) led to significant repression of α-SYN. On the contrary, knocking down of TET1 led to significantly higher expression of α-SYN. However, overexpression of the DNA-hydroxymethylating catalytic domain of TET1 failed to change the expression of α-SYN. Altogether, we showed that TET1 is a repressor for SNCA, and a CXXC domain of TET1 is the primary mediator for this repressive action independent of its hydroxymethylation activity. TET1 levels in PD patients are significantly lower than that in the controls. Conclusions We identified that TET1 acts as a repressor for SNCA by binding the intron1 regions of the gene. As a high level of α-SYN is strongly implicated in the pathogenesis of PD, discovering a repressor for the gene encoding α-SYN is highly important for developing novel therapeutic strategies for the disease.

Summary: Here, we found that heterozygous null of peroxisomal Nudt7 (Nudt7+/−) induced the typical NAFLD features, i.e. increased levels of hepatic triglyceride (TG) and fatty acid (FA), infiltration of inflammatory cells, impaired glucose tolerance and insulin sensitivity, and stimulation of lipolysis from adipose tissue. Particularly, in Nudt7+/− hepatocytes, de novo lipogenesis (DNL) was significantly increased. Ingenuity pathway analysis (IPA) and KEGG pathway analysis of RNA sequencing data suggested the activation of PPAR signaling in the liver of Nudt7+/− mice. Moreover, accumulation of palmitic acid in Nudt7+/− hepatocyte increased the level of H3K4me3 on the promoters of PPARγ resulting in the activation of PPARγ and induced the DNL in the hepatocytes of Nudt7+/− mice. Moreover, we found that liraglutide significantly reduced typical NAFLD features induced by NUDT7 deficiency. Our data suggest that dysregulation of peroxisomal NUDT7 is responsible for upregulation of hepatic DNL by accumulation of palmitic acid and PPARγ activation.

Abstract Big cats (Genus: Panthera) are among the most threatened mammal groups of the world, owing to hunting, habitat loss, and illegal transnational trade. Conservation genetic studies and effective curbs on poaching are important for the conservation of these charismatic apex predators. A limited number of microsatellite markers exists for Panthera species and researchers often cross-amplify domestic cat microsatellites to study these species. We conducted data mining of seven Panthera genome sequences to discover microsatellites for conservation genetic studies of four threatened big cat species. A total of 32 polymorphic microsatellite loci were identified in silico and tested with 152 big cats, and were found polymorphic in most of the tested species. We propose a set of 12 novel microsatellite markers for use in conservation genetics and wildlife forensic investigations of big cat species. Cumulatively, these markers have a high discriminatory power of one in a million for unrelated individuals and one in a thousand for siblings. Similar PCR conditions of these markers increase the prospects of achieving efficient multiplex PCR assays. This study is a pioneering attempt to synthesise genome wide microsatellite markers for big cats.

Abstract The presence of parapapillary choroidal microvasculature dropout (CMvD) may affect optic nerve head (ONH) perfusion in glaucoma patients, since parapapillary choroidal vessels provide vascular supply to the neighboring ONH. However, it remains to be determined whether the presence of parapapillary CMvD is associated with diminished perfusion in the nearby ONH. The present study investigated the spatial relationship between CMvD and ONH vessel density (ONH-VD) loss in open-angle glaucoma (OAG) eyes using optical coherence tomography angiography (OCT-A). This study included 48 OAG eyes with a single localized CMvD confined to the inferotemporal parapapillary sector and 48 OAG eyes without CMvD, matched for demographic and ocular characteristics. Global and regional ONH-VD values were compared between eyes with and without CMvD. The relationships between ONH-VD outcomes and clinical variables were assessed. ONH-VDs at the inferotemporal ONH sectors corresponding to the CMvD location were significantly lower in eyes with compared to those without CMvD. Multivariable linear regression analyses indicated that a lower inferotemporal ONH-VD was independently associated with CMvD presence and a greater CMvD angular extent (both P

Abstract Growing demands for comprehending complicated nano-scale phenomena in atomic resolution has attracted in-situ transmission electron microscopy (TEM) techniques for understanding their dynamics. However, simple to safe TEM sample preparation for in-situ observation has been limited. Here, we suggested the optical microscopy based micro-manipulating system for transferring TEM samples. By adopting our manipulator system, several types of samples from nano-wires to plate-like thin samples were transferred on micro-electro mechanical systems (MEMS) chip in a single step. Furthermore, the control of electrostatic force between the sample and the probe tip is found to be a key role in transferring process.

Abstract The aim of this study is to develop an automated process for modeling average 3D human body according to body types using both NUBRS-based modeling software Rhinoceros 3D® (Rhino) and Grasshopper as an algorithm editor. First, we categorized men aged 36 to 55 years included in SizeUSA 3D data into the three body types (normal, overweight, and obese), and selected seven samples in each body type. To execute the automated process of generating an average 3D model of their lower bodies in a step-by-step manner, the following procedures were performed: (1) Determine the main reference lines on the 3D-scanned lower bodies, including six horizontal reference lines and six vertical reference lines; (2) Create horizontal and vertical line grids and intersection points (3) Generate an average 3D model in a position that corresponds to the average coordinates of the intersection points (vertex coordinates) of seven samples for each body type. A Grasshopper algorithm was formulated to automatically execute all procedures that had to be repeatedly performed. As a way to verify the average model’s size and shape, the girth measurements of the samples for each body type were averaged, and the results were compared with those of the 3D average body shape. It was found that the deviation was less than 1 cm, which indicates the validity of the 3D modeling approach applied in the present study. Each process was incorporated into commands available in the Rhino interface, and this automation allowed a number of 3D body shape modeling operations to be implemented in a significantly reduced time period.

Metallic van der Waals magnets have considerable technological promise, due to their ability to be strongly coupled with electronic currents and integrated in two dimensional heterostructures. Here, Seo et al. demonstrate highly tunable itinerant antiferromagnetism in a van der Waals magnet.

Patients with advanced chronic kidney disease (CKD) experience multiple bothersome symptoms, undermining their quality of life (QOL). With growing attention to the importance of symptom management in advanced CKD, the evidence regarding symptoms is increasing. In this review, we briefly summarize the current evidence of effective pharmacologic and nonpharmacologic interventions to improve symptoms and QOL in patients with advanced CKD, including those on dialysis. We focused on symptoms that are commonly experienced by patients, such as pain, fatigue, sleep disturbances, itching, nausea and vomiting, cognitive impairment, and anxiety and depression. We noted that research in symptom science focused on improving symptom management in CKD is still very limited. In addition to the lack of clinical practice guidelines to address those common symptoms, the major gaps in the current literature include the evidence regarding mechanistic pathways to inform the development of effective symptom management for CKD populations, the evidence to confirm effective pharmacologic interventions in other populations for CKD populations, and research on how to incorporate effective symptom management approaches into clinical care. Although improving mortality remains as an important area in the kidney community, there is an urgent need to focus on improving symptom management to improve QOL in advanced CKD.

With advances in the development of surgical and medical treatments for congenital heart disease (CHD), the population of children and adults with CHD is growing. This population requires multiple surgical and diagnostic imaging procedures. Therefore, general anesthesia is inevitable. In many studies, it has been reported that children with CHD have increased anesthesia risks when undergoing noncardiac surgeries compared to children without CHD. The highest risk group included patients with functional single ventricle, suprasystemic pulmonary hypertension, left ventricular outflow obstruction, and cardiomyopathy. In this review, we provide an overview of perioperative risks in children with CHD undergoing noncardiac surgeries and anesthetic considerations in patients classified as having the highest risk.

Abstract Epigenetic deregulation of α‐synuclein plays a key role in Parkinson’s disease (PD). Analysis of the SNCA promoter using the ENCODE database revealed the presence of important histone post‐translational modifications (PTMs) including transcription‐promoting marks, H3K4me3 and H3K27ac, and repressive mark, H3K27me3. We investigated these histone marks in post‐mortem brains of controls and PD patients and observed that only H3K4me3 was significantly elevated at the SNCA promoter of the substantia nigra (SN) of PD patients both in punch biopsy and in NeuN‐positive neuronal nuclei samples. To understand the importance of H3K4me3 in regulation of α‐synuclein, we developed CRISPR/dCas9‐based locus‐specific H3K4me3 demethylating system where the catalytic domain of JARID1A was recruited to the SNCA promoter. This CRISPR/dCas9 SunTag‐JARID1A significantly reduced H3K4me3 at SNCA promoter and concomitantly decreased α‐synuclein both in the neuronal cell line SH‐SY5Y and idiopathic PD‐iPSC derived dopaminergic neurons. In sum, this study indicates that α‐synuclein expression in PD is controlled by SNCA’s histone PTMs and modulation of the histone landscape of SNCA can reduce α‐synuclein expression.

Abstract Choroidal microvasculature dropout (CMvD) implies compromised optic nerve head perfusion in glaucoma patients. However, there are conflicting findings whether office-hour systemic blood pressure (BP) is related to the presence of CMvD. The present study investigated which systemic BP parameters, derived from 24-h ambulatory BP monitoring (ABPM), are associated with CMvD as assessed by optical coherence tomography angiography (OCT-A) in normal-tension glaucoma (NTG). This study included 88 eyes of 88 NTG patients who underwent 24-h ABPM and OCT-A imaging. Various systemic BP parameters associated with the presence of CMvD were evaluated using logistic regression analyses. CMvD was detected in 38 NTG eyes (43.2%). NTG eyes with CMvD had nighttime diastolic BP (DBP) dip of greater magnitude and longer duration than eyes without CMvD. In multivariate logistic regression, worse VF mean deviation (MD) (odds ratio [OR] 0.786; P = 0.001), greater nighttime DBP dip “%” (OR 1.051; P = 0.034), and higher daytime peak IOP (OR 1.459; P = 0.013) were significantly associated with the presence of CMvD. Based on our findings that the eyes with CMvD are closely associated with having nighttime DBP dip, NTG patients with CMvD should be recommended to undergo 24-h ABPM.

S. patholobus suberectus Dunn, a traditional Chinese herbal medicine, has various pharmacological activities, such as anti-inflammatory properties. However, to the best of our knowledge, its therapeutic effect on atopic dermatitis (AD) has not been investigated. In this study, we explored the effect of S. suberectus Dunn water extract (SSWex) on AD in vivo and in vitro. In Dermatophagoides farina extract (DfE)–treated NC/Nga mice, the oral administration of SSWex alleviated AD-like symptoms, such as ear thickness, dermatitis score, epidermal thickness, immune cell infiltration, and levels of AD-related serum parameters (immunoglobulin E, histamine, and proinflammatory chemokines). In HaCaT cells, the production of proinflammatory chemokines induced by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) was inhibited by SSWex pretreatment. SSWex treatment inhibited the phosphorylation of mitogen-activated protein kinase and activation and translocation of transcriptional factors, such as signal transducer and activator of transcription 1 and nuclear factor kappa B in IFN-γ/TNF-α–stimulated HaCaT cells. These results indicate that SSWex may be developed as an efficient therapeutic agent for AD.

Study of structural inhomogeneities in zeolites is important but limited by conventional techniques. Here the authors employ in situ free-electron-laser-based time-resolved coherent X-ray diffraction imaging to visualize the effect of these inhomogeneities during catalytic deoxygenation of NOx.

Observation of a strain-gradient-induced piezoresponse at domain walls remains a challenge. Here, the authors find the piezoelectric response to be enhanced in the ferroelastic domain walls of centrosymmetric tungsten trioxide thin films due to a large strain gradient over a wide width of the wall.

Abstract Larotrectinib is an orally administered drug and the first and only selective pan-tropomyosin receptor kinase (TRK) inhibitor in clinical development to treat cancer patients harboring a neurotrophic receptor tyrosine kinase gene fusion. In this study, an analytical method to quantify the TRK inhibitor in mouse and human plasma was developed and validated using LC-MS/MS following protein precipitation with acetonitrile. Larotrectinib and an internal standard (carbamazepine) were separated from endogenous substances using an Xterra C18 column with acetonitrile containing 0.1% formic acid as the mobile phase. The ions m/z 429.8 → 342.8 for larotrectinib and m/z 237.0 → 194.0 for carbamazepine detected in multiple reaction monitoring mode were used for the quantitation. The detector response of larotrectinib was linear within the concentration range 5–10,000 ng/mL with a correlation coefficient (r 2) of not less than 0.999. The intra- and inter-day precision and accuracy were less than 10.48% and within − 8.99%, respectively, in mouse and human plasma. Larotrectinib was stable under various storage and handling conditions, and no significant matrix effect was observed in both mouse and human plasma. Finally, the assay was successfully applied to the pharmacokinetic study of larotrectinib after its intravenous and oral administration to mice.

Purpose The purpose of this study was to explore the structure of variables in studies related to unmarried mothers (UMs) based on Neuman's systems model, and the stressors and stress responses of UMs. Methods Whittemore and Knafl’s methodology for integrative reviews was applied. The literature was searched using five electronic databases (KISS, KMbase, KoreaMed, NDSL, and RISS) and a total of 99 variables were collected from 15 studies published between 2009 and 2019. Results The main stressors for UMs were a sense of loss and burden caused by childbirth and childrearing. The main stress responses were parenting stress and depression, respectively. Within the basic structure of variables related to UMs, self-esteem played a crucial role by helping UMs adapt to their situation. Meanwhile, social support of UMs was significantly correlated with parenting stress, depression, and self-esteem. Conclusion In order to understand UMs' stress, is necessary to explore their sense of loss, burden, and self-esteem. Furthermore, it is important to assess the level of parenting stress and depression of UMs and to provide effective interventions to alleviate these stressors. The results of this study provide useful knowledge that can be applied to nursing assessment and interventions for stress management in UMs.

The research to utilize chemical potential mismatch for materials synthesis has been limited across the oxide interface. Here, the authors show that directional ionic transport from the VO2 layers stabilizes the rutile TiO2 phase at extremely low temperatures, at which epitaxy is difficult, by effectively lowering the activation barrier for crystallization.

Abstract The objectives of this study are to identify the principal components that represent distinctive shapes from the silhouette and profile views of the lower body shapes of abdominal obese Korean men and to categorize their body types. Using 3D scans of 625 men aged 35–64 in the 6th SizeKorea dataset, 173 scans (27.7%) of men in ‘abdominal obese’ category (BMI value of 25, waist girth to height ratio of 0.53, and waist girth to hip girth ratio of 0.9 or higher) were utilized. We developed a script to measure 38 items such as front/back crotch length and front/back depths and angles using the SNU-BM program, which is a script-based automated 3D body scan measurement software. The measurements used for principal component (PC) analysis were 31 drops, 2 heights, 2 lengths and 4 angles. Ten PCs representing distinctive silhouettes and profiles of lower body shapes were extracted. The PCs were interpreted as follows: abdomen prominence, thigh to knee profile, upper buttocks prominence, waist to hip drop, thigh to knee silhouette, lower body tilt angle, waist to crotch length, vertical height, abdomen to crotch height, and lower buttocks slope. The three body shape groups were categorized using a K means cluster analysis with ten PC scores. Group 1 had a flat abdomen but prominent buttocks. Group 2 had a developed abdomen and buttocks with vertical thighs. Group 3 had drooped buttocks with tilted thighs.

Low social capital has been reported to be associated with depression in adolescents. In general, adolescents with immigrant backgrounds lack social capital. By employing a latent profile analysis (LPA) for the specification of social capital among multicultural adolescents, depression interventions can be explored through the framework of social capital. The purpose of this study was to identify distinct latent profiles of social capital and explore the depressive symptoms of multicultural adolescents in those profiles. Data of 1,244 adolescents from the Multicultural Adolescents Panel Survey (MAPS) were used, which was conducted for 3rd-year middle school students in 2016. An LPA was used to identify profiles by different social capital classes and Quade's non-parametric ANCOVA was used to confirm the differences in depressive symptoms between profiles. Latent profile analysis indicated four classes. Analysis revealed that there were differences in the level of depressive symptoms according to the social capital sub-profiles (F = 44.42, p < 0.001). Class 1 had the lowest level of depressive symptoms (13.91 ± 4.43) and Class 4 had the highest level (18.07 ± 5.25). The depressive symptoms scores of Classes 2 and 3 were 16.49 ± 5.27 and 16.74 ± 4.95, respectively. These findings provide insight into the interplay between social capital and depressive symptoms among multicultural adolescents. Support in consideration of differences in social capital is needed to reduce depression among multicultural adolescents.