PAF remodels the DREAM complex to bypass cell quiescence and promote lung tumorigenesis.

The DREAM complex orchestrates cell quiescence and the cell cycle. However, how the DREAM complex is deregulated in cancer remains elusive. Here, we report that PAF (PCLAF/KIAA0101) drives cell quiescence exit to promote lung tumorigenesis by remodeling the DREAM complex. PAF is highly expressed in lung adenocarcinoma (LUAD) and is associated with poor prognosis. Importantly, Paf knockout markedly suppressed LUAD development in mouse models. PAF depletion induced LUAD cell quiescence and growth arrest. PAF is required for the global expression of cell-cycle genes controlled by the repressive DREAM complex. Mechanistically, PAF inhibits DREAM complex formation by binding to RBBP4, a core DREAM subunit, leading to transactivation of DREAM target genes. Furthermore, pharmacological mimicking of PAF-depleted transcriptomes inhibited LUAD tumor growth. Our results unveil how the PAF-remodeled DREAM complex bypasses cell quiescence to promote lung tumorigenesis and suggest that the PAF-DREAM axis may be a therapeutic vulnerability in lung cancer.

Targeting of plasmodesmal proteins requires unconventional signals.

Effective cellular signaling relies on precise spatial localization and dynamic interactions among proteins in specific subcellular compartments or niches, such as cell-to-cell contact sites and junctions. In plants, endogenous and pathogenic proteins gained the ability to target plasmodesmata, membrane-lined cytoplasmic connections, through evolution to regulate or exploit cellular signaling across cell wall boundaries. For example, the receptor-like membrane protein PLASMODESMATA-LOCATED PROTEIN 5 (PDLP5), a potent regulator of plasmodesmal permeability, generates feed-forward or feed-back signals important for plant immunity and root development. However, the molecular features that determine the plasmodesmal association of PDLP5 or other proteins remain largely unknown, and no protein motifs have been identified as plasmodesmal targeting signals. Here, we developed an approach combining custom-built machine-learning algorithms and targeted mutagenesis to examine PDLP5 in Arabidopsis thaliana and Nicotiana benthamiana. We report that PDLP5 and its closely related proteins carry unconventional targeting signals consisting of short stretches of amino acids. PDLP5 contains 2 divergent, tandemly arranged signals, either of which is sufficient for localization and biological function in regulating viral movement through plasmodesmata. Notably, plasmodesmal targeting signals exhibit little sequence conservation but are located similarly proximal to the membrane. These features appear to be a common theme in plasmodesmal targeting.

Climate change and public health: The effects of global warming on the risk of allergies and autoimmune diseases: The effects of global warming on the risk of allergies and autoimmune diseases.

Global climate change and extreme weather events are associated with epigenetic modifications in immune cells, leading to the possible increased risk and prevalence of allergies and autoimmune diseases.

Age and sex-related differences in outcomes of OHCA patients after adjustment for sex-based in-hospital management disparities.

OBJECTIVES: Out-of-hospital cardiac arrest (OHCA) survival differences due to sex remain controversial. Previous studies adjusted for prehospital variables, but not sex-based in-hospital management disparities. We aimed to investigate age and sex-related differences in survival outcomes in OHCA patients after adjustment for sex-based in-hospital management disparities. METHODS: This retrospective observational study used a prospective multicenter OHCA registry to review data of patients from October 2015 to December 2020. The primary outcome was good neurological outcome defined as cerebral performance category score 1 or 2. We performed multivariable logistic regression and restricted cubic spline analysis according to age. RESULTS: Totally, 8988 patients were analyzed. Women showed poorer prehospital characteristics and received fewer coronary angiography, percutaneous coronary interventions, targeted temperature management, and extracorporeal membrane oxygenation than men. Good neurological outcomes were lower in women than in men (5.8% vs. 12.2%, p < 0.001). After adjustment for age, prehospital variables, and in-hospital management, women were more likely to have good neurological outcomes than men (adjusted odds ratio [aOR] 1.37, 95% confidence interval [CI] 1.07-1.74, p = 0.012). The restricted cubic spline curve showed a reverse sigmoid pattern of adjusted predicted probability of outcomes and dynamic associations of sex and age-based outcomes. CONCLUSIONS: Women with OHCA were more likely to have good neurological outcome after adjusting for age, prehospital variables, and sex-based in-hospital management disparities. There were non-linear associations between sex and survival outcomes according to age and age-related sex-based differences.

Bright diffusion sign: A sensitive and specific radiologic biomarker for multinodular and vacuolating neuronal tumor.

BACKGROUND AND PURPOSE: Accurate differentiation between multinodular and vacuolating neuronal tumor (MVNT) and dysembryoplastic neuroepithelial tumor (DNET) is important for treatment decision-making. We aimed to develop an accurate radiologic diagnostic model for differentiating MVNT from DNET using T2WI and diffusion-weighted imaging (DWI). MATERIALS AND METHODS: A total of 56 patients (mean age, 47.48±17.78 years; 31 women) diagnosed with MVNT (n = 37) or DNET (n = 19) who underwent brain MRI, including T2WI and DWI, were included. Two board-certified neuroradiologists performed qualitative (bubble appearance, cortical involvement, bright diffusion sign, and bright apparent diffusion coefficient [ADC] sign) and quantitative (nDWI and nADC) assessments. A diagnostic tree model was developed with significant and reliable imaging findings using an exhaustive chi-squared Automatic Interaction Detector (CHAID) algorithm. RESULTS: In visual assessment, the imaging features that showed high diagnostic accuracy and interobserver reliability were the bright diffusion sign and absence of cortical involvement (bright diffusion sign: accuracy, 94.64 %; sensitivity, 91.89 %; specificity, 100.00 %; interobserver agreement, 1.00; absence of cortical involvement: accuracy, 92.86 %; sensitivity, 89.19 %; specificity, 100.00 %; interobserver agreement, 1.00). In quantitative analysis, nDWI was significantly higher in MVNT than in DENT (1.52 ± 0.34 vs. 0.91 ± 0.27, p < 0.001), but the interobserver agreement was fair (intraclass correlation coefficient = 0.321). The overall diagnostic accuracy of the tree model with visual assessment parameters was 98.21 % (55/56). CONCLUSION: The bright diffusion sign and absence of cortical involvement are accurate and reliable imaging findings for differentiating MVNT from DNET. By using simple, intuitive, and reliable imaging findings, such as the bright diffusion sign, MVNT can be accurately differentiated from DNET.

A conformation-selective protein binder for a KRAS mutant inhibits the interaction between RAS and RAF.

Small GTPases are key signaling nodes that regulate the cellular processes and subcellular events, and their abnormal activities and dysregulations are closely linked with diverse cancers. Here, we report the development of conformation-selective protein binders for a KRAS mutant. The conformation-specific protein binders were selected from a repebody scaffold composed of LRR (Leucine-rich repeat) modules through phage display and modular engineering against constitute active conformation of KRAS. Epitope of the selected binders was mapped to be located close to switch I of KRAS. The conformation-selective protein binders were shown to effectively block the interaction between active KRAS and RAS-binding domain of BRAF, suppressing the KRAS-mediated downstream signaling.

Facilitating viral vector movement enhances heterologous protein production in an established plant system.

Molecular farming technology using transiently transformed Nicotiana plants offers an economical approach to the pharmaceutical industry to produce an array of protein targets including vaccine antigens and therapeutics. It can serve as a desirable alternative approach for those proteins that are challenging or too costly to produce in large quantities using other heterologous protein expression systems. However, since cost metrics are such a critical factor in selecting a production host, any system-wide modifications that can increase recombinant protein yields are key to further improving the platform and making it applicable for a wider range of target molecules. Here, we report on the development of a new approach to improve target accumulation in an established plant-based expression system that utilizes viral-based vectors to mediate transient expression in Nicotiana benthamiana. We show that by engineering the host plant to support viral vectors to spread more effectively between host cells through plasmodesmata, protein target accumulation can be increased by up to approximately 60%.

National-scale investigation of dual nitrate isotopes and chloride ion in South Korea: Nitrate source apportionment for stream water.

Nitrate sources in surface water have been identified using dual-isotope compositions of nitrate with various tools to efficiently manage the water quality at the local scale. Correlation between Cl and NO3 has also been used to identify NO3. In this study, we assess the reliability of the dual-isotope approach and Cl in terms of nitrate source apportionment. To this end, we collected stream water samples throughout South Korea to estimate nitrate sources in streams and determine whether the land-use pattern was closely related to nitrate sources. The δ15N-NO3 ranging from -1.3 to 14.8‰ showed a spatial distribution that was lower in mountain ranges (<7‰) than plain areas (>8‰). The Cl concentration in this national-scale distribution was also assessed. The relationship between the proportion of Cl and δ15N-NO3 classifies nitrate sources into areas characterized by three land-use patterns: (1) agricultural and business areas, (2) forests in highlands, and (3) lowland forests, of which (1) had proportions of Cl >50%, while (2) and (3) were <50%. The samples in (3) showed δ15N-NO3 values > 6‰, similar to those of (1). Deuterium excess of samples was negatively correlated (R2 = 0.53) with δ15N-NO3, accounting for the fact that δ15N-NO3 reflected land-use patterns. Samples were dominantly affected by agriculture-derived sources and domestic sewage showed NO3/Cl of <0.4 and δ15N-NO3 of >6‰. These results suggest that nitrate source apportionment should be comprehensively evaluated considering the dual-isotope approach, land-use patterns, and Cl proportions.

A multi-modal wildfire prediction and early-warning system based on a novel machine learning framework.

Wildfires are increasingly impacting the environment and human health. Among the top 20 California wildfires, those in 2020-2021 burned more acres than the last century combined. Lack of an adequate early warning system impacts the health and safety of vulnerable populations disproportionately and widens the inequality gap. In this project, a multi-modal wildfire prediction and early warning system has been developed based on a novel spatio-temporal machine learning architecture. A comprehensive wildfire database with over 37 million data points was created, including the historical wildfires, environmental and meteorological sensor data from the Environmental Protection Agency, and geological data. The data was augmented into 2.53 km × 2.53 km square grids to overcome the sensor network coverage limitations. Leading and trailing indicators for the wildfires are proposed, classified, and tested. The leading indicators are correlated to the risks of wildfire conception, whereas the trailing indicators are correlated to the byproducts of the wildfires. Additionally, geological data was incorporated to provide additional information for better assessment on wildfire risks and propagation. Next, a novel U-Convolutional Long Short-Term Memory (ULSTM) neural network was developed to extract key spatial and temporal features of the dataset, specifically to address the spatial nature of the location of the wildfire and time-progression temporal nature of the wildfire evolution. Through iterative improvements and optimization, the final ULSTM network architecture, trained with data from 2012 to 2017, achieved >97% accuracy for predicting wildfires in 2018, as compared to ∼76% using traditional Convolutional Neural Network (CNN) techniques. The final model was applied to conduct a retrospective study for the 2018-2022 wildfire seasons, and successfully predicted 85.7% of wildfires >300 K acres in size. This technique could enable fire departments to anticipate and prevent wildfires before they strike and provide early warnings for at-risk individuals for better preparation, thereby saving lives, protecting the environment, and avoiding economic damages.

Comparison of Fused Diffusion-Weighted Imaging Using Unenhanced MRI and Abbreviated Post-Contrast-Enhanced MRI in Patients with Breast Cancer.

Background and Objectives: To determine the percentage of breast cancers detectable by fused diffusion-weighted imaging (DWI) using unenhanced magnetic resonance imaging (MRI) and abbreviated post-contrast-enhanced MRI. Materials and Methods: Between October 2016 and October 2017, 194 consecutive women (mean age, 54.2 years; age range, 28-82 years) with newly diagnosed unilateral breast cancer, who underwent preoperative 3.0 T breast MRI with DWI, were evaluated. Both fused DWI and abbreviated MRI were independently reviewed by two radiologists for the detection of index cancer (which showed the most suspicious findings in both breasts), location, lesion conspicuity, lesion type, and lesion size. Moreover, the relationship between cancer detection and histopathological results of surgical specimens was evaluated. Results: Index cancer detection rates were comparable between fused DWI and abbreviated MRI (radiologist 1: 174/194 [89.7%] vs. 184/194 [94.8%], respectively, p = 0.057; radiologist 2: 174/194 [89.7%] vs. 183/194 [94.3%], respectively, p = 0.092). In both radiologists, abbreviated MRI showed a significantly higher lesion conspicuity than fused DWI (radiologist 1: 9.37 ± 2.24 vs. 8.78 ± 3.03, respectively, p < 0.001; radiologist 2: 9.16 ± 2.32 vs. 8.39 ± 2.93, respectively, p < 0.001). The κ value for the interobserver agreement of index cancer detection was 0.67 on fused DWI and 0.85 on abbreviated MRI. For lesion conspicuity, the intraclass correlation coefficients were 0.72 on fused DWI and 0.82 on abbreviated MRI. Among the histopathological factors, tumor invasiveness was associated with cancer detection on both fused DWI (p = 0.011) and abbreviated MRI (p = 0.004, radiologist 1), lymphovascular invasion on abbreviated MRI (p = 0.032, radiologist 1), and necrosis on fused DWI (p = 0.031, radiologist 2). Conclusions: Index cancer detection was comparable between fused DWI and abbreviated MRI, although abbreviated MRI showed a significantly better lesion conspicuity.

TMEM9-v-ATPase Activates Wnt/ß-Catenin Signaling Via APC Lysosomal Degradation for Liver Regeneration and Tumorigenesis.

BACKGROUND AND AIMS: How Wnt signaling is orchestrated in liver regeneration and tumorigenesis remains elusive. Recently, we identified transmembrane protein 9 (TMEM9) as a Wnt signaling amplifier. APPROACH AND RESULTS: TMEM9 facilitates v-ATPase assembly for vesicular acidification and lysosomal protein degradation. TMEM9 is highly expressed in regenerating liver and hepatocellular carcinoma (HCC) cells. TMEM9 expression is enriched in the hepatocytes around the central vein and acutely induced by injury. In mice, Tmem9 knockout impairs hepatic regeneration with aberrantly increased adenomatosis polyposis coli (Apc) and reduced Wnt signaling. Mechanistically, TMEM9 down-regulates APC through lysosomal protein degradation through v-ATPase. In HCC, TMEM9 is overexpressed and necessary to maintain ß-catenin hyperactivation. TMEM9-up-regulated APC binds to and inhibits nuclear translocation of ß-catenin, independent of HCC-associated ß-catenin mutations. Pharmacological blockade of TMEM9-v-ATPase or lysosomal degradation suppresses Wnt/ß-catenin through APC stabilization and ß-catenin cytosolic retention. CONCLUSIONS: Our results reveal that TMEM9 hyperactivates Wnt signaling for liver regeneration and tumorigenesis through lysosomal degradation of APC.

Right ventricular diastolic dysfunction and failure: a review.

Right ventricular diastolic dysfunction and failure (RVDDF) has been increasingly identified in patients with cardiovascular diseases, including heart failure and other diseases with cardiac involvement. It is unknown whether RVDDF exists as a distinct clinical entity; however, its presence and degree have been shown to be a sensitive marker of end-organ dysfunction related to multiple disease processes including systemic hypertension, pulmonary hypertension, heart failure, and endocrine disease. In this manuscript, we review issues pertaining to RVDDF including anatomic features of the right ventricle, physiologic measurements, RVDDF diagnosis, underlying mechanisms, clinical impact, and clinical management. Several unique features of RVDDF are also discussed.

Factors Affecting Pathologic Complete Remission in Patients with Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy.

INTRODUCTION: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is associated with improvement in survival outcomes. This study evaluated the pCR in patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer after NAC. METHODS: We evaluated 417 patients who were diagnosed with invasive breast cancer and treated with NAC followed by curative surgery between January 2007 and December 2020 and analyzed the pCR for HR-positive and HER2-negative breast cancer. RESULTS: The median age at the time of surgery was 45.4 years, and 9.1% of patients (38 of 417) with HR-positive/HER2-negative status had pCR. Among patients with HR-positive/HER2-negative breast cancer, patients with single HR-positivity had a 20.2% pCR rate, and patients with double HR-positivity had a 4.4% pCR rate. Patients with a high Ki-67 index exhibited a higher pCR rate than those with a lower Ki-67 index (14.5% vs. 3.2%). Patients with single HR-positive and high Ki-67 values exhibited a significantly higher pCR rate than those with double HR-positive and low Ki-67 values (27.8% vs. 2.1%; p < 0.001). CONCLUSION: NAC could improve prognosis in patients with HR-positive/HER2-negative breast cancer with a single HR-positive and high Ki-67 values.

Chronic effects of nano and microplastics on reproduction and development of marine copepod Tigriopus japonicus.

This study aimed to examine the impact of chronic (30 days) exposure to polystyrene microplastics (PS-MPs) of different sizes (50 nm and 2 µm) and at different concentrations (0.5 µg/L and 100 mg/L) to marine copepod Tigriopus japonicus. Polystyrene microplastics affected survival rates in size- and concentration-dependent manners. The LC50s values of 50 nm and 2 µm PS-MPs were 0.10 mg/L and 3.92 mg/L, respectively. The developmental time was delayed by 50 nm PS-MPs, and Usp expression was downregulated. Reproduction was negatively affected by 2 µm PS-MPs even at environmentally relevant concentrations; however, the expression of Vtg was not altered. The production rates of reactive oxygen species and nitric oxide also increased after exposure to PS-MPs; but this effect was independent of particle size. The expression levels of Cat and Tnf, genes related to oxidative stress and inflammation, respectively, were upregulated by exposure to PS-MPs, independently of particle size. Meanwhile, the level of oxidative stress in T. japonicus was not significantly affected by PS-MPs at environmentally relevant concentrations. This study suggests that nano-sized PS-MPs are not always more toxic than micro-sized PS-MPs, and that oxidative stress is a key factor in determining the toxic effect on T. japonicus at high concentrations.

A new algorithm to train hidden Markov models for biological sequences with partial labels.

BACKGROUND: Hidden Markov models (HMM) are a powerful tool for analyzing biological sequences in a wide variety of applications, from profiling functional protein families to identifying functional domains. The standard method used for HMM training is either by maximum likelihood using counting when sequences are labelled or by expectation maximization, such as the Baum-Welch algorithm, when sequences are unlabelled. However, increasingly there are situations where sequences are just partially labelled. In this paper, we designed a new training method based on the Baum-Welch algorithm to train HMMs for situations in which only partial labeling is available for certain biological problems. RESULTS: Compared with a similar method previously reported that is designed for the purpose of active learning in text mining, our method achieves significant improvements in model training, as demonstrated by higher accuracy when the trained models are tested for decoding with both synthetic data and real data. CONCLUSIONS: A novel training method is developed to improve the training of hidden Markov models by utilizing partial labelled data. The method will impact on detecting de novo motifs and signals in biological sequence data. In particular, the method will be deployed in active learning mode to the ongoing research in detecting plasmodesmata targeting signals and assess the performance with validations from wet-lab experiments.

Hypoxia-inducible factor 2α is a novel inhibitor of chondrocyte maturation.

Hypoxic environment is essential for chondrocyte maturation and longitudinal bone growth. Although hypoxia-inducible factor 1 alpha (Hif-1α) has been known as a key player for chondrocyte survival and function, the function of Hif-2α in cartilage is mechanistically and clinically relevant but remains unknown. Here we demonstrated that Hif-2α was a novel inhibitor of chondrocyte maturation through downregulation of Runx2 stability. Mechanistically, Hif-2α binding to Runx2 inhibited chondrocyte maturation by Runx2 degradation through disrupting Runx2/Cbfß complex formation. The Hif-2α-mediated-Runx2 degradation could be rescued by Cbfß transfection due to the increase of Runx2/Cbfß complex formation. Consistently, mesenchymal cells derived from Hif-2α heterozygous mice were more rapidly differentiated into hypertrophic chondrocytes than those of wild-type mice in a micromass culture system. Collectively, these findings demonstrate that Hif-2α is a novel inhibitor for chondrocyte maturation by disrupting Runx2/Cbfß complex formation and consequential regulatory activity.

Clinicopathological Features of BRCA1/2 Mutation-Positive Breast Cancer.

PURPOSE: The BRCA1/2 gene is the most well-known and studied gene associated with hereditary breast cancer. BRCA1/2 genetic testing is widely performed in high-risk patients of hereditary breast cancer in Korea. This study aimed to investigate the clinicopathological characteristics of BRCA1/2 mutation-positive breast cancer patients. METHODS: The clinical data of 188 Korean breast cancer patients who underwent genetic testing of BRCA1/2 mutation between March 2015 and February 2020 at Pusan National University Yangsan Hospital were retrospectively reviewed. The characteristics of breast cancer according to the expression of BRCA1 and BRCA2 mutations were analyzed using the Health Insurance Review and Assessment Service guideline criteria and other clinicopathological factors. RESULTS: The factor associated with BRCA1/2 gene expression was cancer stage, and mutation expression was significantly decreased in stage I compared to stage 0 (p = 0.033; odds ratio [OR], 0.169; 95% confidence interval [CI], 0.033-0.867), and there was a tendency to increase in stage II (p = 0.780; OR, 1.150; 95% CI, 0.432-3.064). BRCA1 was significantly associated with triple-negative breast cancer (TNBC) (p = 0.004; OR, 5.887; 95% CI, 1.778-19.498). Gene expression of BRCA2 was significantly reduced under 40 years of age (p = 0.040; OR, 0.198; 95% CI, 0.042-0.930). There was no difference in disease-free survival (p = 0.900) and overall survival (p = 0.733) between the BRCA1/2 mutation-positive and -negative groups. CONCLUSION: In this study, the clinicopathological characteristics of breast cancer patients with BRCA1/2 gene mutations were identified. BRCA1 gene expression was highly correlated with TNBC. BRCA1/2 mutation did not have a poor prognosis regarding recurrence and death.

Clinical utility of cerebrospinal fluid vitamin D-binding protein as a novel biomarker for the diagnosis of viral and bacterial CNS infections.

BACKGROUND: Rapid and accurate diagnosis of central nervous system (CNS) infections is important, and laboratory tests help diagnose CNS infections. Even when the patient has symptoms, laboratory tests often do not reveal any specific findings. The potential of vitamin D-binding protein (VDBP) to be used as a biomarker for viral and bacterial CNS infections was studied. METHODS: A total of 302 subjects with suspected CNS infection who underwent lumbar puncture were included. Clinical and laboratory data were collected retrospectively. VDBP levels were measured in the cerebrospinal fluid (CSF) samples. Genotyping for the GC gene encoding VDBP was also performed. VDBP levels were analyzed and compared by CNS infection, pathogen, CSF opening pressure, and GC genotype. RESULTS: A CNS infection group (n = 90) and a non-CNS infection group (n = 212) were studied. In terms of its receiver operating characteristic, CSF VDBP showed an area under the curve of 0.726 for the diagnosis of CNS infection. CSF VDBP levels were significantly different between the CNS infection and non-infection groups. The CNS infection group with enterovirus showed a statistically lower distribution of CSF VDBP levels than the other virus groups. The group with CSF opening pressure > 25 cmH2O showed higher CSF VDBP levels than the other groups. There was no significant difference in GC gene allele distribution between the CNS infection and non-infection groups. CONCLUSIONS: CSF VDBP levels were increased in patients with CNS infection. The CSF VDBP showed potential as a new biomarker for viral and bacterial CNS infections.

Population genetic structure of Semisulcospira gottschei: simultaneous examination of mtDNA and microsatellite markers.

Semisulcospira gottschei is an Asian endemic species inhabiting Korea and China. However, genetic structure analysis of the resource management of this species has not been performed. To investigate the genetic diversity among populations, microsatellites can be used to determine the geographic origins of marine and freshwater species. This study investigated the genetic structures of the Korean and Chinese populations of S. gottschei based on mitochondrial DNA (mtDNA) Cytochrome oxidase subunit I (COI) and polymorphic microsatellite loci developed from Semisulcospira coreana. Analysis of the mtDNA COI sequence revealed 43 haplotypes, which indicated no gene flow between the Korean and Chinese populations. To further elucidate the genetic structures of the Korean and Chinese populations, the population genetics of S. gottschei were analyzed using nine microsatellite markers. The genetic diversity analysis showed an average of 5.25 alleles per locus, with an average allelic richness of 4.02. Excessive homozygosity was found at all loci, which was expected to be due to the presence of null alleles at all loci. Populations of S. gottschei formed two separate clusters according to pairwise FST and AMOVA. Also, the UPGMA tree, PCA, STRUCTURE, and GeneClass indicated separation of the 11 populations into two clusters: Korea and China. These results have potential use in the management, restoration, and distinction of the origin country of populations.

Comparative analysis of the association between various serum vitamin D biomarkers and sarcopenia.

BACKGROUND: Vitamin D status is associated with muscle strength and maintenance of muscle fibers. However, which serum vitamin D biomarker better reflects sarcopenia remains unclear. The aim of this study was to investigate associations between various serum vitamin D biomarkers (total 25-hydroxy vitamin D [25(OH)D], bioavailable 25(OH)D, 24,25-dihydroxyvitamin D [24,25(OH)2 D], and vitamin D metabolite ratio [VMR]) and sarcopenia. METHODS: The data for 83 hip fracture patients were finally included in the analysis. Sarcopenia was defined according to the Asia Working Group for Sarcopenia (AWGS) criteria. Measurements of 24,25(OH)2 D and 25(OH)D were made using solid-phase extraction (SPE) and subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS). Vitamin D binding protein (VDBP) concentration was measured using an enzyme-linked immunosorbent assay. The VMR was calculated by dividing serum 24,25(OH)2 D by serum 25(OH)D and then multiplying by 100. Based on total 25(OH)D, VDBP, and albumin concentrations, bioavailable 25(OH)D concentrations were calculated using the equations from the other previous studies. RESULTS: Bioavailable 25(OH)D levels were significantly (p = 0.030) decreased in the sarcopenia group compared with the non-sarcopenia group. Results of ROC analysis for the diagnosis of sarcopenia using serum level of bioavailable of 25(OH)D revealed that the cutoff point for bioavailable 25(OH)D was 1.70 ng/ml (AUC = 0.649, p < 0.001). In the group with a bioavailable 25(OH)D less than 1.70 ng/ml, the incidence of sarcopenia increased by 3.3 times (odds ratio: 3.33, p = 0.013). CONCLUSION: We demonstrated that bioavailable 25(OH)D was associated with sarcopenia among the various serum vitamin D biomarkers. Bioavailable vitamin D might be helpful for assessing the risk of sarcopenia.