Actomyosin organelle functions of SPIRE actin nucleators precede animal evolution.

An important question in cell biology is how cytoskeletal proteins evolved and drove the development of novel structures and functions. Here we address the origin of SPIRE actin nucleators. Mammalian SPIREs work with RAB GTPases, formin (FMN)-subgroup actin assembly proteins and class-5 myosin (MYO5) motors to transport organelles along actin filaments towards the cell membrane. However, the origin and extent of functional conservation of SPIRE among species is unknown. Our sequence searches show that SPIRE exist throughout holozoans (animals and their closest single-celled relatives), but not other eukaryotes. SPIRE from unicellular holozoans (choanoflagellate), interacts with RAB, FMN and MYO5 proteins, nucleates actin filaments and complements mammalian SPIRE function in organelle transport. Meanwhile SPIRE and MYO5 proteins colocalise to organelles in Salpingoeca rosetta choanoflagellates. Based on these observations we propose that SPIRE originated in unicellular ancestors of animals providing an actin-myosin driven exocytic transport mechanism that may have contributed to the evolution of complex multicellular animals.

Anisotropic Liesegang pattern for the nonlinear elastic biomineral-hydrogel complex.

The Liesegang pattern is a beautiful natural anisotropic patterning phenomenon observed in rocks and sandstones. This study reveals that the Liesegang pattern can induce nonlinear elasticity. Here, a Liesegang-patterned complex with biomineral-hydrogel repetitive layers is prepared. This Liesegang-patterned complex is obtained only when the biomineralization is performed under the supersaturated conditions. The Liesegang-patterned complex features a nonlinear elastic response, whereas a complex with a single biomineral shell shows a linear behavior, thus demonstrating that the Liesegang pattern is essential in achieving nonlinear elasticity. The stiff biomineral layers have buffered the concentrated energy on behalf of soft hydrogels, thereby exposing the hydrogel components to reduced stress and, in turn, enabling them to perform the elasticity continuously. Moreover, the nonlinear elastic Liesegang-patterned complex exhibits excellent stress relaxation to the external loading, which is the biomechanical characteristic of cartilage. This stress relaxation allows the bundle of fiber-type Liesegang-patterned complex to endure greater deformation.

Bias correction models for electronic health records data in the presence of non-random sampling.

Electronic health records (EHRs) contain rich clinical information for millions of patients and are increasingly used for public health research. However, non-random inclusion of subjects in EHRs can result in selection bias, with factors such as demographics, socioeconomic status, healthcare referral patterns, and underlying health status playing a role. While this issue has been well documented, little work has been done to develop or apply bias-correction methods, often due to the fact that most of these factors are unavailable in EHRs. To address this gap, we propose a series of Heckman type bias correction methods by incorporating social determinants of health selection covariates to model the EHR non-random sampling probability. Through simulations under various settings, we demonstrate the effectiveness of our proposed method in correcting biases in both the association coefficient and the outcome mean. Our method augments the utility of EHRs for public health inferences, as we show by estimating the prevalence of cardiovascular disease and its correlation with risk factors in the New York City network of EHRs.

High protein-containing new food by cell powder meat.

Demand for a new protein source to replace meat is increasing to solve various issues such as limited resources and food shortages. Diverse protein sources are being developed, but alternative proteins such as plants or insects need to improve people's perceptions and organoleptic properties. Therefore, cell-based meat research is intensively conducted, and most studies are aimed at scale-up and cost-down via the research of scaffolds and culture media. Here, we proposed a new food by cell powder meat (CPM), which has a high protein content and a meaty flavor. The powder was manufactured 76% more cost-effectively with less serum than the conventional culture medium and without 3D scaffold. Due to its comprehensive characteristics, the potential applicability of CPM in the cell-based meat industry could be expected.

Potential lifetime effects caused by cellular uptake of nanoplastics: A review.

Plastics have been used for about 100 years, and daily-use products composed of plastics are now prevalent. As a result, humans are very easily exposed to the plastic particles generated from the daily-use plastics. However, studies on cellular uptake of nanoplastics in "human cells" have only recently begun to attract attention. In previous studies, definitions of nanoplastics and microplastics were vague, but recently, they have been considered to be different and are being studied separately. However, nanoplastics, unlike plastic particles of other sizes such as macro- and microplastics, can be absorbed by human cells, and thus can cause various risks such as cytotoxicity, inflammation, oxidative stress, and even diseases such as cancer82, 83. and diabetes (Fan et al., 2022; Wang et al., 2023). Thus, in this review, we defined microplastics and nanoplastics to be different and described the potential risks of nanoplastics to human caused by cellular uptake according to their diverse factors. In addition, during and following plastic product usage a substantial number of fragments of different sizes can be generated, including nanoplastics. Fragmentation of microplastics into nanoplastics may also occur during ingestion and inhalation, which can potentially cause long-term hazards to human health. However, there are still few in vivo studies conducted on the health effect of nanoplastics ingestion and inhalation.

Lipidomic Analysis of Cervicovaginal Fluid for Elucidating Prognostic Biomarkers and Relevant Phospholipid and Sphingolipid Pathways in Preterm Birth.

Cervicovaginal fluid (CVF) is an excellent specimen for monitoring preterm birth (PTB) as it characterizes cervical metabolites, the vaginal environment, and specific host immune responses. However, extensive lipid analysis of CVF to explain PTB has not been studied. In this study, we performed a systematic analysis combining high-throughput lipid analysis and omics to discover the unique metabolic properties of the cervix. Liquid chromatography-high resolution mass spectrometry successfully detected a total of 190 lipids in the CVF of 30 PTB and 30 term birth (TB) pregnant women. The whole lipidomics dataset analyzed by combining multivariate and univariate statistical analysis revealed 35 lipid biomarkers, including phospholipids and sphingolipids. Remarkably, sphingomyelin, which plays a physiologically essential role in sphingolipids, was significantly downregulated in PTB. Metabolic pathway study provides a close relationship between vaginal microbial organization and cell membrane formation, further supporting the robustness of our findings. Sphingolipids and phospholipids, which were determined to be important lipids for predicting PTB in our study, showed a high value of receiver operating characteristic (ROC) curve >0.7, indicating that a lipid diagnostic test and understanding the mechanism of lipids is highly related to the vaginal microbiome. Therefore, our result has high potential as a predictor of PTB.

Hepatocellular Metabolic Abnormalities Induced by Long-Term Exposure to Novel Brominated Flame Retardant, Hexabromobenzene.

Novel brominated flame retardants (NBFRs) are widely used to avoid environmental accumulation concerns and because of the regulations imposed on classical BFRs. However, recent studies have not revealed the negative effects of NBFR accumulation and exposure on humans. We conducted a metabolomics study on hexabromobenzene (HBB), one of the NBFRs, to investigate its effect on hepatocytes. Gas chromatography-mass spectrometry-based metabolite profiling was performed to observe metabolic perturbations by treating human livertissue-derived HepG2 cell lines with HBB for maximum 21 days. Metabolic pathway enrichment using 17 metabolite biomarkers determined via univariate and multivariate statistical analysis verified that long-term accumulation of HBB resulted in distinct diminution of eight amino acids and five other metabolites. Molecular docking of the biomarker-related enzymes revealed the potential molecular mechanism of hepatocellular response to HBB exposure, which disrupts the energy metabolism of hepatic cells. Collectively, this study may provide insights into the hidden toxicity of bioaccumulating HBB and unveil the risks associated with non-regulated NBFRs.

Uptake of Soil-Residual Diazinon by Rotational Lettuce under Greenhouse Conditions.

Pesticide residue is an increasing concern in rotational crop practices. The pesticide used for the primary crop may re-enter the secondary crop, thus exceeding pesticide levels set by the positive list system (PLS). As such, evaluation of pesticide residue translocated into rotational crops is required for ensuring pesticide safety. In this study, we investigated the residue pattern of diazinon translocated into lettuce as a typical rotational crop in Korea. Diazinon was used to treat greenhouse soil at the maximum annual application rate before crop planting. Diazinon residues in soil and lettuce were investigated using liquid chromatography/tandem mass spectroscopy and a modified quick, easy, cheap, effective, rugged, safe (QuEChERS) method. The limit of quantitation (LOQ) of diazinon was found as 0.005 mg/kg for the plant and soil samples. The recovery of diazinon at the LOQ and 10× the LOQ ranged from 100.2% to 108.7%. The matrix calibration curve showed linearity, with R2 values > 0.998. Diazinon residue in soil dissipated over time after the initial treatment, generating first-order kinetics (R2 = 0.9534) and having a half-life of about 22 days. The uptake ratio (UTR) of diazinon from the soil to the plant ranged from 0.002 to 0.026 over the harvest period. Considering the UTRs, diazinon residue in the edible leaf could exceed the PLS level (0.01 mg/kg) if lettuce is rotated in soil containing >0.357 mg/kg of diazinon. Based on our findings, to comply with the PLS, a 3-month plant-back interval is required following diazinon treatment and/or setting the maximum residue limit of diazinon for lettuce.

Tailoring a Gelatin/Agar Matrix for the Synergistic Effect with Cells to Produce High-Quality Cultured Meat.

Edible scaffolds are needed in cultured meat to mimic meat's three-dimensional structure by organizing cells and replenishing the insufficient meat mass of cells alone. However, there is still a large gap between slaughtered meat and cells developed into tissues using scaffolds. This is mainly due to the difference in size, texture, flavor, and taste. In this study, we develop a coating matrix to modify the surface of textured vegetable protein (TVP), a vegetable cell support, to produce cultured meat having slaughtered meat's essential characteristics. We optimized the fish gelatin/agar matrix's microstructure by controlling the ratio of the two biopolymers, stably introducing a cell adhesive environment on the TVP. By coating the optimized gelatin/agar matrix on the TVP's surface using an easy and fast dipping method, hybrid cultured meat composed of animal cells and plant protein was produced. As the cells proliferated, their synergistic effect permitted the cultured meat's texture, flavor, and taste to reach a level comparable to that of slaughtered meat. The TVP-based cultured meat prepared with the present technology has been recreated as high-quality cultured meat by satisfying five challenging factors: cells, texture, cost, mass, and flavor.

Factors associated with hospital admission and severe outcomes for older patients with COVID-19.

BACKGROUND: Morbidity and death due to coronavirus disease 2019 (COVID-19) experienced by older adults in nursing homes have been well described, but COVID-19's impact on community-living older adults is less studied. Similarly, the previous ambulatory care experience of such patients has rarely been considered in studies of COVID-19 risks and outcomes. METHODS: To investigate the relationship of advanced age (65+), on risk factors associated with COVID-19 outcomes in community-living elders, we identified an electronic health records cohort of older patients aged 65+ with laboratory-confirmed COVID-19 with and without an ambulatory care visit in the past 24 months (n = 47,219) in the New York City (NYC) academic medical institutions and the NYC public hospital system from January 2020 to February 2021. The main outcomes are COVID-19 hospitalization; severe outcomes/Intensive care unit (ICU), intubation, dialysis, stroke, in-hospital death), and in-hospital death. The exposures include demographic characteristics, and those with ambulatory records, comorbidities, frailty, and laboratory results. RESULTS: The 31,770 patients with an ambulatory history had a median age of 74 years; were 47.4% male, 24.3% non-Hispanic white, 23.3% non-Hispanic black, and 18.4% Hispanic. With increasing age, the odds ratios and attributable fractions of sex, race-ethnicity, comorbidities, and biomarkers decreased except for dementia and frailty (Hospital Frailty Risk Score). Patients without ambulatory care histories, compared to those with, had significantly higher adjusted rates of COVID-19 hospitalization and severe outcomes, with strongest effect in the oldest group. CONCLUSIONS: In this cohort of community-dwelling older adults, we provided evidence of age-specific risk factors for COVID-19 hospitalization and severe outcomes. Future research should explore the impact of frailty and dementia in severe COVID-19 outcomes in community-living older adults, and the role of engagement in ambulatory care in mitigating severe disease.

Evaluation of Oral Nutritional Supplementation in the Management of Frailty among the Elderly at Facilities of Community Care for the Elderly.

Adequate nutritional intake in elderly individuals improves frailty. Elderly individuals may exhibit improvements in frailty with the use of community care facilities. Therefore, this study evaluated the effects of nutritional intervention in elderly subjects at community care facilities receiving oral nutritional supplements (ONSs) and determined their nutritional status. Sixty-two elderly individuals using community care facilities were divided into the experimental group (EG) (before [n = 31]/after [n = 28]) and control group (CG) (before [n = 31]/after [n = 25]). Subjects in both groups were treated with ONSs (200 mL/200 kcal) for 90 days. However, those in the EG received the product with increased protein; vitamins A, C, D, and E; phosphorus; calcium; and zinc. The data collected included anthropometric data, dietary assessment findings, frailty status (Korean version of the Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight questionnaire), and nutritional status (Mini Nutritional Assessment, MNA). The changes in the two groups were analyzed using the Mann-Whitney U Wilcoxon signed-rank test. Nutritional intervention increased the weight, body mass index, and lean body mass in the EG (p < 0.05). Protein, calcium, and iron levels increased only in the EG (p < 0.05). The MNA score increased and sum of frailty indicators improved in the EG, and the increase in the MNA score in the EG was greater than that in the CG. This study verified the improved anthropometric data and dietary intake in the EG. Thus, the higher number of pre-frailty elderly individuals at facilities of community care indicates the need for adequate nutritional supplementation for frailty management.

Analysis of multicenter clinical trials with very low event rates.

INTRODUCTION: In a five-arm randomized clinical trial (RCT) with stratified randomization across 54 sites, we encountered low primary outcome event proportions, resulting in multiple sites with zero events either overall or in one or more study arms. In this paper, we systematically evaluated different statistical methods of accounting for center in settings with low outcome event proportions. METHODS: We conducted a simulation study and a reanalysis of a completed RCT to compare five popular methods of estimating an odds ratio for multicenter trials with stratified randomization by center: (i) no center adjustment, (ii) random intercept model, (iii) Mantel-Haenszel model, (iv) generalized estimating equation (GEE) with an exchangeable correlation structure, and (v) GEE with small sample correction (GEE-small sample correction). We varied the number of total participants (200, 500, 1000, 5000), number of centers (5, 50, 100), control group outcome percentage (2%, 5%, 10%), true odds ratio (1, > 1), intra-class correlation coefficient (ICC) (0.025, 0.075), and distribution of participants across the centers (balanced, skewed). RESULTS: Mantel-Haenszel methods generally performed poorly in terms of power and bias and led to the exclusion of participants from the analysis because some centers had no events. Failure to account for center in the analysis generally led to lower power and type I error rates than other methods, particularly with ICC = 0.075. GEE had an inflated type I error rate except in some settings with a large number of centers. GEE-small sample correction maintained the type I error rate at the nominal level but suffered from reduced power and convergence issues in some settings when the number of centers was small. Random intercept models generally performed well in most scenarios, except with a low event rate (i.e., 2% scenario) and small total sample size (n ≤ 500), when all methods had issues. DISCUSSION: Random intercept models generally performed best across most scenarios. GEE-small sample correction performed well when the number of centers was large. We do not recommend the use of Mantel-Haenszel, GEE, or models that do not account for center. When the expected event rate is low, we suggest that the statistical analysis plan specify an alternative method in the case of non-convergence of the primary method.

Relationship between diet quality and sarcopenia in elderly Koreans: 2008-2011 Korea National Health and Nutrition Examination Survey.

BACKGROUND/OBJECTIVES: Given the increasing proportion of the Korean population that is aged 65 years and older, the present study analyzed the relationship between diet quality and sarcopenia in elderly persons by using data from the 2008-2011 Korea National Health and Nutrition Examination Survey (KNHANES). SUBJECTS/METHODS: Data for 3,373 persons aged 65 years and over (men: 1,455, 43.1%) were selected from the 2008-2011 KNHANES. Sarcopenia assessments are based on a formula that divides a subject's appendicular skeletal muscle mass (ASM) by their weight (wt) and multiplies that result by 100 ([ASM/wt] × 100). Sarcopenia is present if the subject's result was less than one standard deviation (SD) below the sex-specific mean for a young reference group. For evaluation of diet quality, data obtained via the 24-hour recall method were used to calculate the Diet Quality Index for Koreans (DQI-K). A general linear model was applied in order to analyze general information and nutritional intake according to sarcopenia status. For analysis of the relationship between diet quality and sarcopenia, a binominal logistic regression analysis was undertaken. RESULTS: The sarcopenia prevalence rate among the study subjects aged 65 years and over was 37.6%. The DQI-K of those without sarcopenia was 3.33 ± 0.04 points, while that of those with sarcopenia was 3.45 ± 0.04 points (P < 0.05). The relationship between diet quality and sarcopenia revealed that subjects aged 75 and older had a poor diet quality, and their odds ratio (OR) of sarcopenia presence was significantly higher (OR: 1.807, 95% confidence interval: 1.003-3.254, P < 0.05). CONCLUSIONS: This study revealed that poor diet quality was related to sarcopenia presence in Koreans aged 75 and older. In order to improve the diet quality of the elderly (aged 75 and older), it is necessary to develop dietary improvement guidelines.

Two Small Intravenous Catheters for High-Rate Contrast Medium Injection for Computed Tomography in Patients Lacking Superficial Veins to Accommodate a Large Catheter.

Objective: To prospectively investigate the feasibility of using 2 small intravenous catheters for high-rate computed tomography (CT) contrast injection in patients lacking superficial veins capable of accommodating ≤ 20-gauge catheters. Materials and Methods: Sixty-eight consecutive eligible adults referred for dynamic liver CT were enrolled; 58 had previously undergone liver CT, including 8 that experienced extravasation. Two 22- or 24-gauge catheters were placed in all patients after 2-5 venipunctures, and 2 mL/kg of contrast agent (370 mg I/mL) was split-administered through both catheters to achieve total flow rate of 4 mL/s. Patients' experience and examination success rate, defined as uneventful scans completed at 4 mL/s or at < 4 mL/s achieving standard image quality in all phases, were analyzed. Quantitative hepatic signal-to-noise and hepatic vascular contrast-to-noise ratios (CNRs) were compared with 30 control examinations scanned at 4 mL/s using an 18-gauge catheter. Results: One case each of extravasation and severe injection pain caused the examination to be aborted. Success rate was 88.2% (60/68; 54 patients scanned at 4 mL/s, 6 at 3.5-3.9 mL/s). Fifty-five of 58 patients (94.8%) that had past CT regarded the venipuncture as more tolerable than (n = 36) or similar to (n = 19) past experiences; 45 of 58 patients (77.6%) found contrast injection less painful than (n = 35) or similar to (n = 10) past experiences. When compared with control examinations, signal-to-noise ratio was similar in all phases (p ≥ 0.502), but the hepatic arterial CNR in arterial phase was slightly inferior (p ≤ 0.047). Conclusion: Using 2 small intravenous catheters can effectively achieve high-rate CT contrast injection in patients lacking adequate superficial veins.

Treatment for occult hepatocellular carcinoma: does it offer survival advantages over symptom-driven treatment?

OBJECTIVE: In order to claim a benefit of screen-based diagnosis for asymptomatic individuals, treatment of occult disease needs to offer survival advantages compared to the treatment of symptomatic disease, yet information on this issue is scarce with regard to hepatocellular carcinoma (HCC) screening. METHODS: A total of 3353 treatment-naïve, consecutive, newly diagnosed HCC patients [age: 57.9 ± 10.3, male: 2,689 (80.2%), hepatitis B virus: 2555 (76.2%)], diagnosed between 2010 and 2013 were analyzed. Data on the mode of detection was prospectively collected at the time of HCC diagnosis and was used to group patients into occult or symptomatic cases. RESULTS: Overall, 643 (19.2%) patients were symptomatic cases. The proportion of patients undergoing resection, radiofrequency ablation or transplantation were lower in symptomatic cases than occult cases (20.8 vs. 56.2%, p < .001). Survival was better in occult cases than symptomatic cases (71.2 vs. 30.4% at three-years, p < .001), with a multivariable-adjusted hazard ratio of 1.40 (95% confidence interval (CI), 1.24-1.58). When stratified by tumor stage, a survival benefit was not observed for patients diagnosed at modified International Union Against Cancer (mUICC) stage I, but presenting symptoms were diverse and nonspecific. In a statistical model adjusting for potential lead-time bias, the association between overall survival and the mode of detection was markedly attenuated and was no longer significant when the treatment modality was included in the model (hazard ratio, 0.94; 95% CI, 0.82-1.07). CONCLUSION: Treatment of occult disease offered a survival benefit to patients over symptomatic cases. These data support screening practices for asymptomatic individuals to diagnose occult HCC.

Evaluation of the Gini Coefficient in Spatial Scan Statistics for Detecting Irregularly Shaped Clusters.

Spatial scan statistics with circular or elliptic scanning windows are commonly used for cluster detection in various applications, such as the identification of geographical disease clusters from epidemiological data. It has been pointed out that the method may have difficulty in correctly identifying non-compact, arbitrarily shaped clusters. In this paper, we evaluated the Gini coefficient for detecting irregularly shaped clusters through a simulation study. The Gini coefficient, the use of which in spatial scan statistics was recently proposed, is a criterion measure for optimizing the maximum reported cluster size. Our simulation study results showed that using the Gini coefficient works better than the original spatial scan statistic for identifying irregularly shaped clusters, by reporting an optimized and refined collection of clusters rather than a single larger cluster. We have provided a real data example that seems to support the simulation results. We think that using the Gini coefficient in spatial scan statistics can be helpful for the detection of irregularly shaped clusters.

A Comparison of Spatial Pattern Detection Methods for Major Cancer Mortality in Korea.

Spatial pattern detection can be a useful tool for understanding the geographical distribution of cancer mortality. This study compared the results from several special analysis methods to examine the geographical variations in Korean major cancer mortality during 2010 to 2013. The spatial scan statistic and Tango's method were used to detect spatial clusters with unusually high or low rates. The local indicator of spatial association was used for cluster detection with accounting for spatial autocorrelation among adjacent areas. A nonparametric approach was used to identify local districts with significantly higher or lower rates, compared to the average national rate. The different methods revealed similar results in the overall patterns, but slightly different specific results. These techniques can provide complementary information and should be used based on the distinguishing features of each method. It may be better to use several different methods for these analyses rather than a single method.

Complete Switch of Selectivity in the C-H Alkenylation and Hydroarylation Catalyzed by Iridium: The Role of Directing Groups.

A complete switch in the Cp*Ir(III)-catalyzed paths between C-H olefination and hydroarylation was found to be crucially dependent on the type of directing groups. This dichotomy in product distribution was correlated to the efficiency in attaining syn-coplanarity of olefin-inserted 7-membered iridacycles. Theoretical studies support our hypothesis that the degree of flexibility of this key intermediate modulates the ß-H elimination, which ultimately affords the observed chemoselectivity.

Iridium(III)-catalyzed C-H amidation of arylphosphoryls leading to a P-stereogenic center.

Direct CH amidation of arylphosphoryl compounds has been developed by using an Ir(III) catalyst system under mild conditions. A wide range of substrates could be employed with high functional-group tolerance. This procedure was successfully applied for the first time to the asymmetric reaction giving rise to a P-chirogenic center with a high diastereomeric ratio of up to 19:1 (90 % de).

Ruthenium-catalyzed direct C-H amidation of arenes including weakly coordinating aromatic ketones.

C-H activation: The ruthenium-catalyzed direct sp(2) C-H amidation of arenes by using sulfonyl azides as the amino source is presented (see scheme). A wide range of substrates were readily amidated including arenes bearing weakly coordinating groups. Synthetic utility of the thus obtained products was demonstrated in the preparation of biologically active heterocycles.