DFT Study on the Janus ZrSSe Monolayer for Its Potential Application in NO Gas Sensing.

The growth of industry has resulted in increased global air pollution, necessitating the urgent development of highly sensitive gas detectors. In this work, the adsorption of the Janus ZrSSe monolayer for CO, CO2, NH3, NO, NO2, and O2 was studied by first-principles calculations. First, the stability of the ZrSSe monolayer is confirmed through calculations of cohesive energy and AIMD simulations. Furthermore, the calculations indicate that the Se layer exhibits higher selectivity and sensitivity toward gas molecules compared to the S layer. Specifically, among the gases adsorbed on the Se layer, NO has the shortest adsorption distance (1.804 Å), the lowest adsorption energy (-0.424 eV), and the greatest electron transfer (0.098 e). Additionally, density of states analysis reveals that adsorption of NO, NO2, and O2 on the Janus ZrSSe monolayer can induce a transition from a nonmagnetic to a magnetic state. The adsorption of NO not only alters the magnetic state but also induces a transition from a semiconductor to metal, which is highly advantageous for gas sensing applications. There results suggest that the Janus ZrSSe monolayer has the potential to serve as a highly sensitive detector for NO gas.

The MYC transcription factor PbrMYC8 negatively regulates PbrMSL5 expression to promote pollen germination in Pyrus.

The successful germination of pollen is essential for double fertilization in flowering plants. Mechanosensitive channels of small conductance (MscS-like, MSL) inhibit pollen germination and maintains cellular integrity of pollen during this process. Therefore, it is vital to carefully regulate the expression of MSL to promote successful pollen germination. Despite its importance, the molecular mechanisms governing MSL expression in plants remain poorly understood. Here, we had identified 15 MSL genes in the pear, among which PbrMSL5 was expressed in pollen development. Subcellular localization experiments revealed that PbrMSL5 was located in both plasma membrane and cytoplasm. Functional investigations, including complementation experiments using the atmsl8 mutant background, demonstrated the involvement of PbrMSL5 in preserving pollen cell integrity and inhibiting germination. Antisense oligonucleotide experiments further confirmed that PbrMSL5 suppressed pear pollen germination by reducing osmotic pressure and Cl- content. Yeast one-hybrid, electrophoretic mobility shift assays, and dual luciferase reporter assay elucidated that PbrMYC8 interacts directly with the N-box element, leading to the suppression of PbrMSL5 expression and promoted pollen germination. These results represented a significant advancement in unraveling the molecular mechanisms controlling plant MSL expression. This study showed valuable contribution to advancing our comprehension of the mechanism underlying pollen germination.

Fungal primary and opportunistic pathogens: an ecological perspective.

Fungal primary pathogenicity on vertebrates is here described as a deliberate strategy where the host plays a role in increasing the species fitness. Opportunism is defined as coincidental survival of an individual strain in host tissue using properties that are designed for life in an entirely different habitat. In that case the host's infection control is largely based on innate immunity, and the etiologic agent is not transmitted after infection, and thus fungal evolution is not possible. Primary pathogens encompass two types, depending on their mode of transmission. Environmental pathogens have a double life cycle, and tend to become enzootic, adapted to a preferred host in a particular habitat. In contrast, pathogens that have a host-to-host transmission pattern are prone to shift to a neighboring, immunologically naive host, potentially leading to epidemics. Beyond these prototypical life cycles, some environmental fungi are able to make large leaps between dissimilar hosts/habitats, probably due to similarity of key factors enabling survival in an entirely different niche, and thus allowing a change from opportunistic to primary pathogenicity. Mostly, such factors seem to be associated with extremotolerance.

Urine metabolite changes after cardiac surgery predict acute kidney injury.

Background: Acute kidney injury (AKI) is a serious complication in patients undergoing cardiac surgery, with the underlying mechanism remaining elusive and a lack of specific biomarkers for cardiac surgery-associated AKI (CS-AKI). Methods: We performed an untargeted metabolomics analysis of urine samples procured from a cohort of patients with or without AKI at 6 and 24 h following cardiac surgery. Based on the differential urinary metabolites discovered, we further examined the expressions of the key metabolic enzymes that regulate these metabolites in kidney during AKI using a mouse model of ischemia-reperfusion injury (IRI) and in hypoxia-treated tubular epithelial cells (TECs). Results: The urine metabolomic profiles in AKI patients were significantly different from those in non-AKI patients, including upregulation of tryptophan metabolism- and aerobic glycolysis-related metabolites, such as l-tryptophan and d-glucose-1-phosphate, and downregulation of fatty acid oxidation (FAO) and tricarboxylic acid (TCA) cycle-related metabolites. Spearman correlation analysis showed that serum creatinine was positively correlated with urinary l-tryptophan and indole, which had high accuracy for predicting AKI. In animal experiments, we demonstrated that the expression of rate-limiting enzymes in glycolysis, such as hexokinase II (HK2), was significantly upregulated during renal IRI. However, the TCA cycle-related key enzyme citrate synthase was significantly downregulated after IRI. In vitro, hypoxia induced downregulation of citrate synthase in TECs. In addition, FAO-related gene peroxisome proliferator-activated receptor alpha (PPARα) was remarkably downregulated in kidney during renal IRI. Conclusion: This study presents urinary metabolites related to CS-AKI, indicating the rewiring of the metabolism in kidney during AKI, identifying potential AKI biomarkers.

The relationship between autoimmune disorders and intracranial aneurysms in East Asian and European populations: a bidirectional and multivariable two-sample Mendelian randomization study.

Background: It remains unclear about the pathogenesis of intracranial aneurysms (IAs) in the setting of autoimmune disorders (ADs). However, the underlying systemic inflammatory characteristics of ADs may affect IAs through shared inflammatory pathways. Therefore, this study was conducted to explore the relationship between ADs and IAs and assess causal effects. Methods: In this study, 6 common ADs were included to explore their causal relationship with IAs. Besides, a bidirectional two-sample univariable Mendelian randomization (UVMR) analysis was performed. In addition, the primary analysis was performed by the inverse variance weighted (IVW) and Bayesian weighted Mendelian randomization (BWMR) method, and a series of sensitivity analyses were performed to assess the robustness of the results. Further, the data related to ADs and IAs were collected from open genome-wide association study studies (GWASs) and the Cerebrovascular Disease Knowledge Portal (CDKP) (including 11,084 cases and 311,458 controls), respectively. These analyses were conducted based on both the East Asian and European populations. Moreover, 6 ADs were subject to grouping according to connective tissue disease, inflammatory bowel disease, and thyroid disease. On that basis, a multivariate MR (MVMR1) analysis was further performed to explore the independent causal relationship between each AD and IAs, and an MVMR 2 analysis was conducted to investigate such potential confounders as smoking, alcohol consumption, and systolic blood pressure. Finally, these results were verified based on the data from another GWAS of IAs. Results: The UVMR analysis results demonstrated that systemic lupus erythematosus (SLE) was associated with a high risk of IAs in the East Asian population (IVW OR, 1.06; 95%CI, 1.02-1.11; p = 0.0065, UVMR), which was supported by the results of BWMR (OR, 1.06; 95%CI, 1.02-1.11; p = 0.0067, BWMR), MVMR1 (OR, 1.06; 95%CI, 1.01-1.10; p = 0.015, MVMR1), MVMR2 (OR, 1.05; 95%CI, 1.00-1.11; p = 0.049, MVMR2), and sensitivity analyses. The results in the validation group also suggested a causal relationship between SLE and IAs (IVW OR, 1.04; 95% CI, 1.00-1.09; p = 0.046). The reverse MR analysis results did not reveal a causal relationship between IAs and ADs. Conclusion: In this MR study, SLE was validated to be a risk factor for IAs in the East Asian population. Therefore, the management of IAs in patients with SLE should be highlighted to avoid stroke events.

PDX1+ cell budding morphogenesis in a stem cell-derived islet spheroid system.

Remarkable advances in protocol development have been achieved to manufacture insulin-secreting islets from human pluripotent stem cells (hPSCs). Distinct from current approaches, we devised a tunable strategy to generate islet spheroids enriched for major islet cell types by incorporating PDX1+ cell budding morphogenesis into staged differentiation. In this process that appears to mimic normal islet morphogenesis, the differentiating islet spheroids organize with endocrine cells that are intermingled or arranged in a core-mantle architecture, accompanied with functional heterogeneity. Through in vitro modelling of human pancreas development, we illustrate the importance of PDX1 and the requirement for EphB3/4 signaling in eliciting cell budding morphogenesis. Using this new approach, we model Mitchell-Riley syndrome with RFX6 knockout hPSCs illustrating unexpected morphogenesis defects in the differentiation towards islet cells. The tunable differentiation system and stem cell-derived islet models described in this work may facilitate addressing fundamental questions in islet biology and probing human pancreas diseases.

Vitamin C inactivates c-Jun N-terminal kinase to stabilize heart and neural crest derivatives expressed 1 (Hand1) in regulating placentation and maintenance of pregnancy.

Vitamin C (VC) serves as a pivotal nutrient for anti-oxidation process, metabolic responses, and stem cell differentiation. However, its precise contribution to placenta development and gestation remains obscure. Here, we demonstrated that physiological levels of VC act to stabilize Hand1, a key bHLH transcription factor vital for the development trajectory of trophoblast giant cell (TGC) lineages, thereby promoting the differentiation of trophoblast stem cells into TGC. Specifically, VC administration inactivated c-Jun N-terminal kinase (JNK) signaling, which directly phosphorylates Hand1 at Ser48, triggering the proteasomal degradation of Hand1. Conversely, a loss-of-function mutation at Ser48 on Hand1 not only significantly diminished both intrinsic and VC-induced stabilization of Hand1 but also underscored the indispensability of this residue. Noteworthy, the insufficiency of VC led to severe defects in the differentiation of diverse TGC subtypes and the formation of labyrinth's vascular network in rodent placentas, resulting in failure of maintenance of pregnancy. Importantly, VC deficiency, lentiviral knockdown of JNK or overexpression of Hand1 mutants in trophectoderm substantially affected the differentiation of primary and secondary TGC in E8.5 mouse placentas. Thus, these findings uncover the significance of JNK inactivation and consequential stabilization of Hand1 as a hitherto uncharacterized mechanism controlling VC-mediated placentation and perhaps maintenance of pregnancy.

Nonparametric receiver operating characteristic curve analysis with an imperfect gold standard.

This article addresses the challenge of estimating receiver operating characteristic (ROC) curves and the areas under these curves (AUC) in the context of an imperfect gold standard, a common issue in diagnostic accuracy studies. We delve into the nonparametric identification and estimation of ROC curves and AUCs when the reference standard for disease status is prone to error. Our approach hinges on the known or estimable accuracy of this imperfect reference standard and the conditional independent assumption, under which we demonstrate the identifiability of ROC curves and propose a nonparametric estimation method. In cases where the accuracy of the imperfect reference standard remains unknown, we establish that while ROC curves are unidentifiable, the sign of the difference between two AUCs is identifiable. This insight leads us to develop a hypothesis-testing method for assessing the relative superiority of AUCs. Compared to the existing methods, the proposed methods are nonparametric so that they do not rely on the parametric model assumptions. In addition, they are applicable to both the ROC/AUC analysis of continuous biomarkers and the AUC analysis of ordinal biomarkers. Our theoretical results and simulation studies validate the proposed methods, which we further illustrate through application in two real-world diagnostic studies.

Novel BiOI/LaOXI〈IX〉 heterojunction with enhanced visible-light driven photocatalytic performance: unveiling the mechanism of interlayer electron transition.

Improving visible light absorption plays an important role in the utilization of solar power for photocatalysis. Using first-principles calculations within the HSE06 functional, we propose that the semiconductor heterojunction BiOI/LaOXI〈IX〉 extends the optical absorption to the near-infrared range, boosts the absorption coefficient from 1.28 × 105 cm-1 to above 2.20 × 105 cm-1 in the visible light range, and increases the conversion efficiency of solar power up to 9.48%. The enhanced optical absorption derives from the significant interlayer transition and excitonic effect which benefit from polarized LaOXI with a flat band in the highest valence band (VB). In BiOI/LaOClI〈ICl 〉, the electrostatic potential difference (ΔΦ) modifies the band edge positions to meet the requirements for photocatalytic overall water splitting, while the polarized electric field (Ep) accelerates the separation of photogenerated carriers and regulates the overpotentials of photogenerated carriers following a direct Z-scheme strategy. In addition, BiOI/LaOXI〈IX〉 is dynamically and thermodynamically stable. Furthermore, only a low external potential is needed to drive the redox reaction. Our theoretical results suggest that BiOI/LaOXI〈IX〉 could be a potential photocatalyst for overall water splitting with enhanced visible light absorption.

Development of a Nomogram That Predicts the Risk of Atrial Fibrillation in Patients with Coronary Heart Disease.

Objective: To explore the risk factors of atrial fibrillation (AF) in patients with coronary heart disease (CHD), and to construct a risk prediction model. Methods: The participants in this case-control study were from the cardiovascular Department of Changzhou Affiliated Hospital of Nanjing University of Chinese Medicine from June 2016 to June 2023, and they were divided into AF group and non-AF group according to whether AF occurred during hospitalization. The clinical data of the two groups were compared by retrospective analysis. Multivariate Logistic regression analysis was used to investigate the risk factors of AF occurrence in CHD patients. The nomogram model was constructed with R 4.2.6 language "rms" package, and the model's differentiation, calibration and effectiveness were evaluated by drawing ROC curve, calibration curve and decision curve. Results: A total of 1258 patients with CHD were included, and they were divided into AF group (n=92) and non-AF group (n=1166) according to whether AF was complicated. Logistic regression analysis showed that age, coronary multiple branch lesion, history of heart failure, history of drinking, pulmonary hypertension, left atrial diameter, left ventricular end-diastolic diameter and diabetes mellitus were independent risk factors for the occurrence of AF in CHD patients (P < 0.05). The ROC curve showed that the AUC of this model was 0.956 (95% CI (0.916, 0.995)) and the consistency index was 0.966. The calibration curve of the model is close to the ideal curve. The analysis of decision curve shows that the prediction value of the model is better when the probability threshold of the model is 0.042~0.963. Conclusion: The nomogram model established in this study for predicting the risk of AF in patients with CHD has better predictive performance and has certain reference value for clinical identification of high-risk groups prone to AF in patients with CHD.

Endocrine Outcomes and Associated Predictive Factors for Somatotrophin Pituitary Adenoma after Endoscopic Endonasal Transsphenoidal Surgery: 10 Years of Experience in a Single Institute.

Objective Biochemical remission rates of endoscopic endonasal transsphenoidal surgery (EETS) and its associated predictive factors were evaluated in patients with somatotrophin pituitary adenomas. Methods The patients who underwent EETS in Jinling Hospital were identified between 2011 and 2020. The surgeons' experience, preoperative insulin-like growth factor 1 (IGF-1), basal growth hormone (GH) levels, nadir GH levels, and the tumor characteristics were analyzed for their relationships with endocrine outcomes. Total 98 patients were included for single factor analysis and regression analysis. They were divided into three groups according to the admission chronologic order. Results The overall remission rate of the patients was 57% (56/98) for all the patients over 10 years. In the single factor analysis, we found that the tumor size, cavernous invasion, and sellar invasion were valuable to predict the endocrine outcome after surgery. As for the suprasellar invasion, no significant difference was found between the noninvasive group and the invasive group. The preoperative IGF-1 level ( p = 0.166), basal GH level ( p = 0.001), and nadir GH level ( p = 0.004) were also different between the remission group and the nonremission group in the single factor analysis. The logistic regression analysis indicated that the preoperative nadir GH (odds ratio = 0.930, 95% confidence interval = 0.891-0.972, p = 0.001) was a significant predictor for the endocrine outcomes after surgery. Conclusion The surgeons' experience is an important factor that can affect the patients' endocrine outcomes after surgery. The macroadenomas with lateral invasion are more difficult to cure. Patients with higher preoperative nadir GH levels are less likely to achieve remission.

Healthcare resource utilisation and costs associated with AL amyloidosis: a retrospective matched cohort study.

We conducted a retrospective population-based, matched cohort study using the National Health Insurance Research Database to estimate healthcare resource utilisation (HRU) and costs in patients with newly diagnosed AL amyloidosis in Taiwan. Cases were matched 10:1 by age, sex, and area of residence to patients without AL amyloidosis (comparators) randomly selected from the database during the same time period. Annual all-cause HRU and costs for 3 years were quantified. AL amyloidosis-attributable costs were obtained by subtracting all-cause HRU costs incurred by comparators from cases. The mean age of all patients was 60.78 years and 59.07% were male. Co-morbidities were more frequent in cases than comparators. By 6 months after diagnosis, 12.1% of cases had died versus 0.9% of comparators. In the first year, cases had 103% more outpatient visits, 177% more emergency room visits, were hospitalised 4-times more frequently, and spent 5.5-times more days in hospital than comparators, and total healthcare costs were > sixfold higher. Costs incurred during the first year after diagnosis accounted for 55% of the 3-year cumulative cost. High HRU costs associated with delayed diagnosis and end-organ damage indicate a need for earlier diagnosis and more effective treatments for AL amyloidosis.

The role of soil structure on the cracking and cadmium leaching behavior of biochar-amended fine-grained soils.

Biochar has shown promising potential for soil remediation, yet its impact on heavy metals (HMs) immobilization often overlooks soil structure, which could influence soil cracking behavior and HMs transport. To address this gap, this study investigates the role of soil structure (dry density and aggregate size) on the cracking and cadmium (Cd) leaching behavior of biochar-amended fine-grained soils. A series of semi-dynamic leaching tests were conducted on samples with and without wetting-drying (W-D) cycles. Based on the proposed improved method for quantifying the effective diffusion coefficient (De) of Cd in unsaturated soils and microstructural analyses, we found that: (1) Higher dry density and larger aggregate generally resulted in smaller De by decreasing soil pore volume. (2) Biochar could connect isolated pores within large aggregates through its internal pores, yielding greater increases in De (294.8%-469.0%) compared to small aggregates (29.1%-77.4%) with 3% biochar. However, further increases in biochar dosage led to decreased De, primarily due to the dense pore structure. (3) Biochar effectively inhibited soil cracking, achieving the highest reduction of 36.8% in surface crack ratio. (4) After W-D cycles, samples exhibited higher De with increasing dry density, with aggravated cracking being the primary cause, suggesting preferential flow within the cracks, particularly those penetrating the soil. This study highlights the importance of careful consideration of soil structure and cracking potential before in situ field application of biochar as a remediation agent for HMs-contaminated fine-grained soils.

Efficient uranium sequestration ability and mechanism of live and inactivated strain of Streptomyces sp. HX-1 isolated from uranium wastewater.

Prokaryotes are effective biosorbents for the recovery of uranium and other heavy metals. However, the potential mechanism of uranium bioaccumulation by filamentous strain (actinobacteria) remains unclear. This study demonstrates the potential for and mechanism of uranium bioaccumulation by living (L-SS) and inactivated (I-SS) Streptomyces sp. HX-1 isolated from uranium mine waste streams. Uranium accumulation experiments showed that L-SS and I-SS had efficient uranium adsorption potentials, with removal rates of 92.93 and 97.42%, respectively. Kinetic and equilibrium data indicated that the bioaccumulation process was consistent with the pseudo-second-order kinetic, Langmuir, and Sips isotherm models. FTIR indicated that the main functional groups of L-SS and I-SS binding uranium were uranyl, carboxyl, and phosphate groups. Moreover, the results of XRD, XPS, SEM-EDS, and TEM-EDS analyses revealed for the first time that L-SS has biomineralization and bioreduction capacity against uranium. L-SS mineralize U(VI) into NH4UO2PO4 and [Formula: see text] through the metabolic activity of biological enzymes (phosphatases). In summary, Streptomyces sp. HX-1 is a novel and efficient uranium-fixing biosorbent for the treatment of uranium-contaminated wastewater.

Radiomics analysis based on CT for predicting lymph node metastasis and prognosis in duodenal papillary carcinoma.

OBJECTIVES: Radiomics has been demonstrated to be strongly associated with TNM stage and patient prognosis. We aimed to develop a model for predicting lymph node metastasis (LNM) and survival. METHODS: For radiomics texture selection, 3D Slicer 5.0.3 software and the least absolute shrinkage and selection operator (LASSO) algorithm were used. Subsequently, the radiomics model, computed tomography (CT) image, and clinical risk model were compared. The performance of the three models was evaluated using receiver operating characteristic (ROC) curves, decision curve analysis (DCA), calibration plots, and clinical impact curves (CICs). RESULTS: For the LNM prediction model, 224 patients with LNM information were used to construct a model that was applied to predict LNM. According to the CT data and clinical characteristics, we constructed a radiomics model, CT imaging model and clinical model. The radiomics model for evaluating LNM status showed excellent calibration and discrimination in the training cohort (AUC = 0.926, 95% CI = 0.869-0.982) and the validation cohort (AUC = 0.872, 95% CI = 0.802-0.941). DeLong's test demonstrated that the difference among the three models was significant. Similarly, DCA and CIC showed that the radiomics model has better clinical utility than the CT imaging model and clinical model. Our model also exhibited good performance in predicting survival-in line with the findings of the model built with clinical risk factors. CONCLUSIONS: CT radiomics models exhibited better predictive performance for LNM than models built based on clinical risk characteristics and CT imaging and had comparative clinical utility for predicting patient prognosis. CRITICAL RELEVANCE STATEMENT: The radiomics model showed excellent performance and discrimination for predicting LNM and survival of duodenal papillary carcinoma (DPC). KEY POINTS: LNM status determines the most appropriate treatment for DPC. Our radiomics model for evaluating the LNM status of DPC performed excellently. The radiomics model had high sensitivity and specificity for predicting survival, exhibiting great clinical value.

GNAS mutations suppress cell invasion by activating MEG3 in growth hormone-secreting pituitary adenoma.

Approximately 30%-40% of growth hormone-secreting pituitary adenomas (GHPAs) harbor somatic activating mutations in GNAS (α subunit of stimulatory G protein). Mutations in GNAS are associated with clinical features of smaller and less invasive tumors. However, the role of GNAS mutations in the invasiveness of GHPAs is unclear. GNAS mutations were detected in GHPAs using a standard polymerase chain reaction (PCR) sequencing procedure. The expression of mutation-associated maternally expressed gene 3 (MEG3) was evaluated with RT-qPCR. MEG3 was manipulated in GH3 cells using a lentiviral expression system. Cell invasion ability was measured using a Transwell assay, and epithelial-mesenchymal transition (EMT)-associated proteins were quantified by immunofluorescence and western blotting. Finally, a tumor cell xenograft mouse model was used to verify the effect of MEG3 on tumor growth and invasiveness. The invasiveness of GHPAs was significantly decreased in mice with mutated GNAS compared with that in mice with wild-type GNAS. Consistently, the invasiveness of mutant GNAS-expressing GH3 cells decreased. MEG3 is uniquely expressed at high levels in GHPAs harboring mutated GNAS. Accordingly, MEG3 upregulation inhibited tumor cell invasion, and conversely, MEG3 downregulation increased tumor cell invasion. Mechanistically, GNAS mutations inhibit EMT in GHPAs. MEG3 in mutated GNAS cells prevented cell invasion through the inactivation of the Wnt/ß-catenin signaling pathway, which was further validated in vivo. Our data suggest that GNAS mutations may suppress cell invasion in GHPAs by regulating EMT through the activation of the MEG3/Wnt/ß-catenin signaling pathway.

Invertible all-optical logic gate on chip.

We demonstrate an invertible all-optical gate on chip, with the roles of control and signal switchable by slightly adjusting their relative arrival time at the gate. It is based on the quantum Zeno blockade (QZB) driven by sum-frequency generation (SFG) in a periodically poled lithium niobate microring resonator. For two nearly identical nanosecond pulses, the later arriving pulse is modulated by the earlier arriving one, resulting in 2.4 and 3.9 power extinction between the two, respectively, when their peak powers are 1 mW and 2 mW, respectively. Our results, while to be improved and enriched, herald a new, to the best of our knowledge, paradigm of logical gates and circuits for exotic applications.

Characterizing Cellular Physiological States with Three-Dimensional Shape Descriptors for Cell Membranes.

The shape of a cell as defined by its membrane can be closely associated with its physiological state. For example, the irregular shapes of cancerous cells and elongated shapes of neuron cells often reflect specific functions, such as cell motility and cell communication. However, it remains unclear whether and which cell shape descriptors can characterize different cellular physiological states. In this study, 12 geometric shape descriptors for a three-dimensional (3D) object were collected from the previous literature and tested with a public dataset of ~400,000 independent 3D cell regions segmented based on fluorescent labeling of the cell membranes in Caenorhabditis elegans embryos. It is revealed that those shape descriptors can faithfully characterize cellular physiological states, including (1) cell division (cytokinesis), along with an abrupt increase in the elongation ratio; (2) a negative correlation of cell migration speed with cell sphericity; (3) cell lineage specification with symmetrically patterned cell shape changes; and (4) cell fate specification with differential gene expression and differential cell shapes. The descriptors established may be used to identify and predict the diverse physiological states in numerous cells, which could be used for not only studying developmental morphogenesis but also diagnosing human disease (e.g., the rapid detection of abnormal cells).

Correction: Valuation of the EQ-5D-5L in Taiwan.

[This corrects the article DOI: 10.1371/journal.pone.0209344.].

Epidemiology, Treatment Patterns, and Healthcare Resource Utilization Study of Patients With Alopecia Areata in Taiwan's National Health Insurance Research Database.

OBJECTIVES: This study investigated the epidemiology, treatment patterns, and resource utilization in patients with alopecia areata (AA) in Taiwan using the National Health Insurance Research Database. AA severity was determined by treatment use and diagnostic codes in the year after enrollment (including corticosteroids, systemic immunosuppressants, topical immunotherapy, and phototherapy). METHODS: The cross-sectional analysis was conducted to estimate the incidence and prevalence of AA from 2016 to 2020. For the longitudinal analysis, 2 cohorts were identified: mild/moderate and severe. The cohorts were matched based on age, gender, and comorbidities. Patients were enrolled upon their first claim with an AA diagnosis during the index period of 2017-2018. RESULTS: The number of patients with AA increased from 3221 in 2016 to 3855 in 2020. The longitudinal analysis identified 1808 mild/moderate patients and 452 severe patients. Mild/moderate patients used higher levels of topical corticosteroids (82.41%) than severe patients (73.45%). Conversely, severe patients used more topical nonsteroids (41.81%) and systemic therapies (51.77%) than mild/moderate patients (0.44% and 16.15%, respectively). Oral glucocorticoids use was higher in severe patients (47.57%) relative to mild/moderate patients (14.88%), whereas the use of injectable forms was similar. The most used systemic immunosuppressants were methotrexate, cyclosporin, and azathioprine. Topical immunotherapy utilization decreased with subsequent treatment lines for severe patients. Treatment persistence at 6 months was low for all treatments. Severe patients had higher annual AA-related outpatient visits than the mild/moderate cohort. CONCLUSIONS: These findings highlight the need for additional innovations and therapies to address the clinical and economic burden of AA.