Predicting protein synergistic effect in Arabidopsis using epigenome profiling.

Histone modifications can regulate transcription epigenetically by marking specific genomic loci, which can be mapped using chromatin immunoprecipitation sequencing (ChIP-seq). Here we present QHistone, a predictive database of 1534 ChIP-seqs from 27 histone modifications in Arabidopsis, offering three key functionalities. Firstly, QHistone employs machine learning to predict the epigenomic profile of a query protein, characterized by its most associated histone modifications, and uses these modifications to infer the protein's role in transcriptional regulation. Secondly, it predicts synergistic regulatory activities between two proteins by comparing their profiles. Lastly, it detects previously unexplored co-regulating protein pairs by screening all known proteins. QHistone accurately identifies histone modifications associated with specific known proteins, and allows users to computationally validate their results using gene expression data from various plant tissues. These functions demonstrate an useful approach to utilizing epigenome data for gene regulation analysis, making QHistone a valuable resource for the scientific community ( https://qhistone.paoyang.ipmb.sinica.edu.tw ).

Surveillance of pathogenic yeasts in hospital environments in Taiwan in 2020.

BACKGROUND: A predominate azole-resistant Candida tropicalis clade 4 genotype causing candidemia has been detected in not only Taiwan but also China, Singapore, and Australia. It can also be detected on fruit surfaces. In addition to determining distribution and drug susceptibilities of pathogenic yeasts in environments of intensive care units of 25 hospitals in Taiwan, we would also like to investigate whether the azole-resistant C. tropicalis exists in Taiwan's hospital environment. METHODS: The swabs of hospital environments were collected from August to November in 2020 and were cultured for yeasts. The yeasts were identified by rDNA sequence and the antifungal susceptibilities of those isolates were determined by the broth microdilution method. RESULTS: The average yeast-culture rate of hospitals was 9.4% (217/2299). Sinks had the highest yeast-positive culture rate (32.7%), followed by bedside tables (28.9%), floors (26.0%), water-dispenser buttons (23.8%), and TV controller/touch panels (19.0%). Of 262 identified isolates, Candida parapsilosis was the most common species, accounting for 22.1%, followed by Filobasidium uniguttulatum (18.3%), Candida albicans (9.5%), C. tropicalis (8.0%), Candida glabrata (Nakaseomyces glabratus) (6.9%), and 30 other species (35.1%). Of the 21 C. tropicalis isolates from 11 units in 9 hospitals, 15 diploid sequence types (DSTs) were identified. The two DST506 fluconazole-resistant ones belonged to clade 4. CONCLUSION: We detected not only various pathogenic yeast species but also the predominant clade 4 genotype of azole-resistant C. tropicalis. Our findings highlight and re-emphasize the importance of regular cleaning and disinfection practices.

Characteristics and Prevalence of Vancomycin-variable Enterococcus faecium bacteremia in southern Taiwan.

BACKGROUND: Vancomycin-variable enterococci (VVE) are vanA-carrying Enterococcus faecium that are phenotypically susceptible to vancomycin and can only be detected using molecular methods, leading to the possibility of treatment failure and posing threats to infection control. This study aimed to determine the prevalence of VVE and its associated clinical risk factors. METHODS: This retrospective study was conducted in two hospitals in southern Taiwan. Patients with phenotypically vancomycin-susceptible E. faecium bacteremia were enrolled between 2017 and 2021. VVEs were defined as isolates harboring the vanA gene that were phenotypically susceptible to vancomycin. Vancomycin-susceptible E. faecium (VSE) isolates were phenotypically susceptible to vancomycin and lacked vanA or vanB genes. RESULTS: Of the 142 enrolled patients, 121 (85.2%) had VSE and 21 (14.8%) had VVE. Resistance rates to penicillin, tetracycline, and fosfomycin were higher in VVE isolates. Malignancy (adjusted odds ratio [aOR] = 4.87; 95% confidence interval [CI] 1.54-15.41, p = 0.007) and central venous catheter usage (aOR = 4.69; 95% CI 1.49-14.78, p = 0.008) were the independent risk factors associated with VVE bacteremia. Being male (aOR = 0.12, CI 0.03-0.44, p = 0.002) was less likely to be associated with VVE bacteremia. Although VVE was not associated with 30-day mortality (38.1% [VVE] vs. 35.5% [VSE], p = 0.822), one case of subsequent vancomycin-resistant enterococci infection in the VVE group with vancomycin treatment (4.8%, 1/21) was identified, which led to subsequent mortality. CONCLUSIONS: The prevalence of VVE was high among E. faecium isolates with vancomycin-susceptible phenotypes in southern Taiwan. Although the current study revealed that VVE bacteremia was not associated with poor clinical outcome, further multicenter surveillance survey is recommended to evaluate the possible impact of VVE on public health in Taiwan.

Cytoplasmic ribosomes on mitochondria alter the local membrane environment for protein import.

Most of the mitochondria proteome is nuclear-encoded, synthesized by cytoplasmic ribosomes, and targeted to mitochondria post-translationally. However, a subset of mitochondrial-targeted proteins is imported co-translationally, although the molecular mechanisms governing this process remain unclear. We employ cellular cryo-electron tomography to visualize interactions between cytoplasmic ribosomes and mitochondria in Saccharomyces cerevisiae. We use surface morphometrics tools to identify a subset of ribosomes optimally oriented on mitochondrial membranes for protein import. This allows us to establish the first subtomogram average structure of a cytoplasmic ribosome on the surface of the mitochondria in the native cellular context, which showed three distinct connections with the outer mitochondrial membrane surrounding the peptide exit tunnel. Further, this analysis demonstrated that cytoplasmic ribosomes primed for mitochondrial protein import cluster on the outer mitochondrial membrane at sites of local constrictions of the outer and inner mitochondrial membrane. Overall, our study reveals the architecture and the spatial organization of cytoplasmic ribosomes at the mitochondrial surface, providing a native cellular context to define the mechanisms that mediate efficient mitochondrial co-translational protein import.

Sex Differences in the Expression of Cardiac Remodeling and Inflammatory Cytokines in Patients with Obstructive Sleep Apnea and Atrial Fibrillation.

Although there is a link between obstructive sleep apnea (OSA) and atrial fibrillation (AF) and numerous investigations have examined the mechanism of AF development in OSA patients, which includes cardiac remodeling, inflammation, and gap junction-related conduction disorder, there is limited information regarding the differences between the sexes. This study analyzes the impact of sex differences on the expression of cardiac remodeling, inflammatory cytokines, and gap junctions in patients with OSA and AF. A total of 154 individuals diagnosed with sleep-related breathing disorders (SRBDs) were enrolled in the study and underwent polysomnography and echocardiography. Significant OSA was defined as an apnea-hypopnea index (AHI) of ≥15 per hour. Exosomes were purified from the plasma of all SRBD patients and incubated in HL-1 cells to investigate their effects on inflammatory cytokines and GJA1 expression. The differences in cardiac remodeling and expression of these biomarkers in both sexes were analyzed. Of the 154 enrolled patients, 110 patients were male and 44 patients were female. The LA sizes and E/e' ratios of male OSA patients with concomitant AF were greater than those of control participants and those without AF (all p < 0.05). Meanwhile, female OSA patients with AF had a lower left ventricular ejection fraction than those OSA patients without AF and control subjects (p < 0.05). Regarding the expression of inflammatory cytokines and GJA1, the mRNA expression levels of GJA1 were lower and those of IL-1ß were higher in those male OSA patients with AF than in those male OSA patients without AF and control subjects (p < 0.05). By contrast, mRNA expression levels of HIF-1α were higher in those female OSA patients with and without AF than in control subjects (p < 0.05). In conclusion, our study revealed sex-specific differences in the risk factors and biomarkers associated with AF development in patients with OSA.

First-year outcomes of very low birth weight preterm singleton infants with hypoxemic respiratory failure treated with milrinone and inhaled nitric oxide (iNO) compared to iNO alone: A nationwide retrospective study.

BACKGROUND: Inhaled nitric oxide (iNO) has a beneficial effect on hypoxemic respiratory failure. The increased use of concurrent iNO and milrinone was observed. We aimed to report the trends of iNO use in the past 15 years in Taiwan and compare the first-year outcomes of combining iNO and milrinone to the iNO alone in very low birth weight preterm (VLBWP) infants under mechanical ventilation. METHODS: This nationwide cohort study enrolled preterm singleton infants with birth weight <1500g treated with iNO from 2004 to 2019. Infants were divided into two groups, with a combination of intravenous milrinone (Group 2, n = 166) and without milrinone (Group 1, n = 591). After propensity score matching (PSM), each group's sample size is 124. The primary outcomes were all-cause mortality and the respiratory condition, including ventilator use and duration. The secondary outcomes were preterm morbidities within one year after birth. RESULTS: After PSM, more infants in Group 2 needed inotropes. The mortality rate was significantly higher in Group 2 than in Group 1 from one month after birth till 1 year of age (55.1% vs. 13.5%) with the adjusted hazard ratio of 4.25 (95%CI = 2.42-7.47, p <0.001). For infants who died before 36 weeks of postmenstrual age (PMA), Group 2 had longer hospital stays compared to Group 1. For infants who survived after 36 weeks PMA, the incidence of moderate and severe bronchopulmonary dysplasia (BPD) was significantly higher in Group 2 than in Group 1. For infants who survived until one year of age, the incidence of pneumonia was significantly higher in Group 2 (28.30%) compared to Group 1 (12.62%) (p = 0.0153). CONCLUSION: Combined treatment of iNO and milrinone is increasingly applied in VLBWP infants in Taiwan. This retrospective study did not support the benefits of combining iNO and milrinone on one-year survival and BPD prevention. A future prospective study is warranted.

Classification Prediction of Alzheimer's Disease and Vascular Dementia Using Physiological Data and ECD SPECT Images.

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common forms of dementia. However, their neuropsychological and pathological features often overlap, making it difficult to distinguish between AD and VaD. In addition to clinical consultation and laboratory examinations, clinical dementia diagnosis in Taiwan will also include Tc-99m-ECD SPECT imaging examination. Through machine learning and deep learning technology, we explored the feasibility of using the above clinical practice data to distinguish AD and VaD. We used the physiological data (33 features) and Tc-99m-ECD SPECT images of 112 AD patients and 85 VaD patients in the Taiwanese Nuclear Medicine Brain Image Database to train the classification model. The results, after filtering by the number of SVM RFE 5-fold features, show that the average accuracy of physiological data in distinguishing AD/VaD is 81.22% and the AUC is 0.836; the average accuracy of training images using the Inception V3 model is 85% and the AUC is 0.95. Finally, Grad-CAM heatmap was used to visualize the areas of concern of the model and compared with the SPM analysis method to further understand the differences. This research method can quickly use machine learning and deep learning models to automatically extract image features based on a small amount of general clinical data to objectively distinguish AD and VaD.

Comparative analyses of the Smith-Magenis syndrome protein RAI1 in mice and common marmoset monkeys.

Retinoic acid-induced 1 (RAI1) encodes a transcriptional regulator critical for brain development and function. RAI1 haploinsufficiency in humans causes a syndromic autism spectrum disorder known as Smith-Magenis syndrome (SMS). The neuroanatomical distribution of RAI1 has not been quantitatively analyzed during the development of the prefrontal cortex, a brain region critical for cognitive function and social behaviors and commonly implicated in autism spectrum disorders, including SMS. Here, we performed comparative analyses to uncover the evolutionarily convergent and divergent expression profiles of RAI1 in major cell types during prefrontal cortex maturation in common marmoset monkeys (Callithrix jacchus) and mice (Mus musculus). We found that while RAI1 in both species is enriched in neurons, the percentage of excitatory neurons that express RAI1 is higher in newborn mice than in newborn marmosets. By contrast, RAI1 shows similar neural distribution in adult marmosets and adult mice. In marmosets, RAI1 is expressed in several primate-specific cell types, including intralaminar astrocytes and MEIS2-expressing prefrontal GABAergic neurons. At the molecular level, we discovered that RAI1 forms a protein complex with transcription factor 20 (TCF20), PHD finger protein 14 (PHF14), and high mobility group 20A (HMG20A) in the marmoset brain. In vitro assays in human cells revealed that TCF20 regulates RAI1 protein abundance. This work demonstrates that RAI1 expression and protein interactions are largely conserved but with some unique expression in primate-specific cells. The results also suggest that altered RAI1 abundance could contribute to disease features in disorders caused by TCF20 dosage imbalance.

Clinical validation of a saliva-based matrix metalloproteinase-1 rapid strip test for detection of oral cavity cancer.

BACKGROUND: We previously identified matrix metalloproteinase-1 (MMP-1) as one of the most promising salivary biomarkers for oral squamous cell carcinoma (OSCC) and developed a sensitive ELISA for MMP-1 with good performance in detection of OSCC using a cohort of 1160 saliva samples. METHODS: A time-saving rapid strip test (RST) for MMP-1 was developed in this study and its diagnostic performance compared with ELISA using saliva samples from a new cohort of 603 subjects (171 healthy controls, 236 patients with oral potentially malignant disorders, and 196 OSCC patients). RESULTS: Salivary MMP-1 levels measured using RST and ELISA were highly comparable and both assays could effectively distinguish between OSCC and non-cancerous groups. Similar to ELISA, receiver operating characteristic curve analysis of the MMP-1 RST was effective in identifying patients with OSCC at different oral cavity sites and stages. CONCLUSIONS: Salivary MMP-1 can be sensitively detected using both RST and ELISA methods. Our newly developed point-of-care MMP-1 RST is a promising in vitro diagnostic device (IVD) that may serve as a novel auxiliary tool in the routine clinical detection and monitoring of OSCC.

Comparison between a novel salivary marker and several clinical prognosticators in oral cavity cancer.

Objectives: This study aimed to investigate the association between salivary matrix metalloproteinase-1 (MMP-1) and clinicopathological parameters of oral cavity squamous cell carcinoma (OSCC) and compare the prognostic efficacy of salivary MMP-1 and other established circulating markers for OSCC. Methods: Saliva specimens from 479 OSCC subjects were examined using an enzyme-linked immunosorbent assay. The area under the curve (AUC) values of salivary MMP-1 and other markers were calculated, and survival analyses were conducted using Kaplan-Meier and multivariate regression methods. Results: Salivary MMP-1 showed good discrimination in predicting overall survival, with an AUC of 0.638, which was significantly higher than that of albumin (0.530, p = .021) and Charlson comorbidity index (0.568, p = .048) and comparable with neutrophil-to-lymphocyte ratio (0.620, p = .987), platelet-to-lymphocyte ratio (0.575, p = .125), and squamous cell carcinoma antigen (0.609, p = .605). Elevated levels of salivary MMP-1 were significantly associated with higher pT classification, pN classification, overall pathological stage, positive extranodal extension, tumor differentiation, positive lymphovascular invasion, positive perineural invasion, and tumor depth (p all <.05). Multivariate analyses indicated that a higher level of salivary MMP-1 (≥2060.0 pg/mL) was an independent predictive factor of poorer overall survival (adjusted hazard ratio: 1.421 [95% confidential interval: 1.014-1.989], p = .041). Conclusion: The study found that the salivary MMP-1 level was significantly associated with many adverse clinicopathological parameters of OSCC. In OSCC, it was found to have superior efficacy in predicting prognosis and was an independent prognostic factor of post-treatment outcome. Level of evidence: 3.

Estimating genome-wide DNA methylation heterogeneity with methylation patterns.

BACKGROUND: In a heterogeneous population of cells, individual cells can behave differently and respond variably to the environment. This cellular diversity can be assessed by measuring DNA methylation patterns. The loci with variable methylation patterns are informative of cellular heterogeneity and may serve as biomarkers of diseases and developmental progression. Cell-to-cell methylation heterogeneity can be evaluated through single-cell methylomes or computational techniques for pooled cells. However, the feasibility and performance of these approaches to precisely estimate methylation heterogeneity require further assessment. RESULTS: Here, we proposed model-based methods adopted from a mathematical framework originally from biodiversity, to estimate genome-wide DNA methylation heterogeneity. We evaluated the performance of our models and the existing methods with feature comparison, and tested on both synthetic datasets and real data. Overall, our methods have demonstrated advantages over others because of their better correlation with the actual heterogeneity. We also demonstrated that methylation heterogeneity offers an additional layer of biological information distinct from the conventional methylation level. In the case studies, we showed that distinct profiles of methylation heterogeneity in CG and non-CG methylation can predict the regulatory roles between genomic elements in Arabidopsis. This opens up a new direction for plant epigenomics. Finally, we demonstrated that our score might be able to identify loci in human cancer samples as putative biomarkers for early cancer detection. CONCLUSIONS: We adopted the mathematical framework from biodiversity into three model-based methods for analyzing genome-wide DNA methylation heterogeneity to monitor cellular heterogeneity. Our methods, namely MeH, have been implemented, evaluated with existing methods, and are open to the research community.

Long non-coding RNA FKSG29 regulates oxidative stress and endothelial dysfunction in obstructive sleep apnea.

Altered expressions of pro-/anti-oxidant genes are known to regulate the pathophysiology of obstructive sleep apnea (OSA).We aim to explore the role of a novel long non-coding (lnc) RNA FKSG29 in the development of intermittent hypoxia with re-oxygenation (IHR)-induced endothelial dysfunction in OSA. Gene expression levels of key pro-/anti-oxidant genes, vasoactive genes, and the FKSG29 were measured in peripheral blood mononuclear cells from 12 subjects with primary snoring (PS) and 36 OSA patients. Human monocytic THP-1 cells and human umbilical vein endothelial cells (HUVEC) were used for gene knockout and double luciferase under IHR exposure. Gene expression levels of the FKSG29 lncRNA, NOX2, NOX5, and VEGFA genes were increased in OSA patients versus PS subjects, while SOD2 and VEGFB gene expressions were decreased. Subgroup analysis showed that gene expression of the miR-23a-3p, an endogenous competitive microRNA of the FKSG29, was decreased in sleep-disordered breathing patients with hypertension versus those without hypertension. In vitro IHR experiments showed that knock-down of the FKSG29 reversed IHR-induced ROS overt production, early apoptosis, up-regulations of the HIF1A/HIF2A/NOX2/NOX4/NOX5/VEGFA/VEGFB genes, and down-regulations of the VEGFB/SOD2 genes, while the protective effects of FKSG29 knock-down were abolished by miR-23a-3p knock-down. Dual-luciferase reporter assays confirmed that FKSG29 was a sponge of miR-23a-3p, which regulated IL6R directly. Immunofluorescence stain further demonstrated that FKSGH29 knock-down decreased IHR-induced uptake of oxidized low density lipoprotein and reversed IHR-induced IL6R/STAT3/GATA6/ICAM1/VCAM1 up-regulations. The findings indicate that the combined RNA interference may be a novel therapy for OSA-related endothelial dysfunction via regulating pro-/anti-oxidant imbalance or targeting miR-23a-IL6R-ICAM1/VCAM1 signaling.

Smith-Magenis syndrome protein RAI1 regulates body weight homeostasis through hypothalamic BDNF-producing neurons and neurotrophin downstream signalling.

Retinoic acid-induced 1 (RAI1) haploinsufficiency causes Smith-Magenis syndrome (SMS), a genetic disorder with symptoms including hyperphagia, hyperlipidemia, severe obesity, and autism phenotypes. RAI1 is a transcriptional regulator with a pan-neural expression pattern and hundreds of downstream targets. The mechanisms linking neural Rai1 to body weight regulation remain unclear. Here we find that hypothalamic brain-derived neurotrophic factor (BDNF) and its downstream signalling are disrupted in SMS (Rai1+/-) mice. Selective Rai1 loss from all BDNF-producing cells or from BDNF-producing neurons in the paraventricular nucleus of the hypothalamus (PVH) induced obesity in mice. Electrophysiological recordings revealed that Rai1 ablation decreased the intrinsic excitability of PVHBDNF neurons. Chronic treatment of SMS mice with LM22A-4 engages neurotrophin downstream signalling and delayed obesity onset. This treatment also partially rescued disrupted lipid profiles, insulin intolerance, and stereotypical repetitive behaviour in SMS mice. These data argue that RAI1 regulates body weight and metabolic function through hypothalamic BDNF-producing neurons and that targeting neurotrophin downstream signalling might improve associated SMS phenotypes.

MoS2 as an Effective Cu Diffusion Barrier with a Back-End Compatible Process.

This study demonstrates molybdenum disulfide (MoS2) as a superior candidate as a diffusion barrier and liner. This research explores a newly developed process to show how effectively MoS2 can be applied. First, a new approach is developed to prepare molybdenum disulfide (MoS2) by microwave plasma-enhanced sulfurization (MW-PES). MW-PES can rapidly and directly grow on the target substrate at low temperatures, which is compatible with the back-end-of-line (BEOL) technology. Second, the performance of MW-PES MoS2 as a diffusion barrier and liner is reported in the subsequent section. Through time-dependent dielectric breakdown (TDDB) measurements, MoS2 is shown to have a barrier property better than that of the current material, Ta, with the same thickness. According to the model fitting, the lifetime of the device is about 45.2 times the lifetime under normal operating conditions. Furthermore, MoS2 shows its superior thermal stability in maintaining the barrier properties. MoS2 is proven to be an excellent interface as a liner as it can provide sufficient adhesion and wettability to further effectively reduce the surface scattering of copper (Cu) and significantly lower the circuit resistance.

Magnusiomyces Capitatus Lung Nodule in a Patient with Nasopharyngeal and Hepatocellular Carcinoma.

Magnusiomyces capitatus is a dimorphic yeast commonly isolated from the environment and was uncommonly reported as a disease in Asia. It may cause invasive infection in patients with hematological malignancies, especially those with neutropenia, and resulting in high mortality. Herein, we reported a man with nasopharyngeal carcinoma and hepatocellular carcinoma suffered from intermittent fever after pulmonary nodules resection. The histopathology showed yeast-like fungal elements. For further identification, we extracted the tissue DNA from formalin-fixed paraffin-embedded tissue and M. capitatus was confirmed using polymerase chain reaction amplification and sequencing of the ITS region of ribosomal DNA. After a 4-week amphotericin B and flucytosine treatment, his condition recovered well and then was followed by a 3-month oral fluconazole treatment. There was no evidence of recurrence within one year. Our case highlights that nucleic acids obtained from formalin-fixed tissue could be a feasible identification method, especially in those whose culture results are unavailable.

Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturation.

Pancreatic islets are three-dimensional cell aggregates consisting of unique cellular composition, cell-to-cell contacts, and interactions with blood vessels. Cell aggregation is essential for islet endocrine function; however, it remains unclear how developing islets establish aggregation. By combining genetic animal models, imaging tools, and gene expression profiling, we demonstrate that islet aggregation is regulated by extracellular matrix signaling and cell-cell adhesion. Islet endocrine cell-specific inactivation of extracellular matrix receptor integrin ß1 disrupted blood vessel interactions but promoted cell-cell adhesion and the formation of larger islets. In contrast, ablation of cell-cell adhesion molecule α-catenin promoted blood vessel interactions yet compromised islet clustering. Simultaneous removal of integrin ß1 and α-catenin disrupts islet aggregation and the endocrine cell maturation process, demonstrating that establishment of islet aggregates is essential for functional maturation. Our study provides new insights into understanding the fundamental self-organizing mechanism for islet aggregation, architecture, and functional maturation.

Effect of immunological non-response on incidence of Non-AIDS events in people living with HIV: A retrospective multicenter cohort study in Taiwan.

BACKGROUND: People living with HIV (PLWH) are susceptible to non-AIDS-related events, particularly those with immunological nonresponses (INRs) to highly active antiretroviral therapy (HAART). This study assessed the association of INRs with incident non-AIDS-related events among PLWH. METHODS: This multicenter retrospective cohort study enrolled PLWH who had newly diagnosed stage 3 HIV and received HAART between January 1, 2008, and December 31, 2019. The patients were divided into two groups according to their immunological responses on the 360th day after HAART initiation: INR and non-INR groups. Cox regression and sensitivity analyses were conducted to estimate the effects of INRs on overall and individual categories of non-AIDS-related events (malignancies, vascular diseases, metabolic disorders, renal diseases, and psychiatric disorders). Patient observation started on the 360th day after HAART initiation and continued until February 28, 2022, death, or an outcome of interest, whichever occurred first. RESULTS: Among the 289 included patients, 44 had INRs. Most of the included patients were aged 26-45 years (69.55%) and were men who have sex with men (89.97%). Many patients received HIV diagnoses between 2009 and 2012 (38.54%). INRs (vs. non-INRs) were associated with composite non-AIDS-related events (adjusted hazard ratio [aHR] = 1.80; 95% confidence interval [CI]: 1.19-2.73) and metabolic disorders (aHR = 1.75; 95% CI: 1.14-2.68). Sensitivity analyses revealed consistent results for each Cox regression model for both composite non-AIDS-related events and metabolic diseases. CONCLUSION: Clinicians should be vigilant and implement early intervention and rigorous monitoring for non-AIDS-related events in PLWH with INRs to HAART.

High-resolution three-dimensional structural determination of unstained double-gyroid block copolymers through scanning transmission electron microscopy.

Block copolymer-based multicomponent materials have garnered considerable attention because of tunable properties due to their various constituents. The use of electron tomography through transmission electron microscopy (TEM) for the three-dimensional (3D) imaging of stained block copolymers is an established approach for investigating structure-property relationships. Recently, scanning transmission electron microscopy (STEM) with an annular dark-field (ADF) detector has emerged as a method for the 3D structural analysis of unstained block copolymers. However, because of a lack of electron contrast, only a few low-resolution 3D reconstructions were reported for light elements. Herein, we report the first 3D structural analysis of a 200-nm-thick film composed of unstained double-gyroid block copolymers-polystyrene-b-poly(2-vinylpyridine) (PS-P2VP)-at a resolution of 8.6 nm through spherical aberration Cs-corrected STEM. At this resolution, P2VP molecules can be distinguished from PS molecules in z-contrast 3D reconstructions obtained both experimentally and theoretically. The 3D reconstructions revealed structural differences between stained and unstained specimens.

Optimal Frequency of Hepatitis C Virus (HCV) RNA Testing for Detection of Acute HCV Infection Among At-risk People With Human Immunodeficiency Virus: A Multicenter Study.

Using 3-stage pooled-plasma hepatitis C virus (HCV) RNA testing performed quarterly among at-risk people with human immunodeficiency virus (PWH), we found that if testing had been performed every 6 or 12 months, 58.6%-91.7% of PWH who recently acquired HCV would be delayed for diagnosis and might contribute to onward HCV transmission with longer durations.