Recent strategies for triplet-state emission regulation toward non-lead organic-inorganic metal halides.

Organic-inorganic metal halides (OIMHs) have strengthened the development of triplet-state emission materials due to their excellent luminescence performance. Due to the inherent toxicity of lead (Pb) significantly limiting its further advancement, numerous studies have been conducted to regulate triplet-state emission of non-Pb OIMHs, and several feasible strategies have been proposed. However, most of the non-Pb OIMHs reported have a relatively short lifetime or a low luminescence efficiency, not in favor of their application. In this review, we provide a summary of recent reports on the regulation of triplet-state emissions in non-Pb OIMHs to provide benefits for the design of innovative luminescent materials. Our focus is primarily on exploring the internal and external factors that influence the triplet-state emission. Starting from the luminescence mechanism, the current strategies for regulating triplet-state emissions are summarized. Moreover, by manipulating these strategies, it becomes feasible to achieve triplet-state emissions that span a range of colors from blue to red, and even extend into the near-infrared spectrum with high luminescence efficiency, while also increasing their lifetimes. This review not only provides fresh insights into the advancement of triplet-state emissions in OIMHs but also integrates experimental and theoretical perspectives to illuminate the trajectory of future research endeavors.

Dissecting the effects of METTL3 on alternative splicing in prostate cancer.

Although the role of METTL3 has been extensively studied in many cancers, its role in isoform switching in prostate cancer (PCa) has been poorly explored. To investigate its role, we applied standard RNA-sequencing and long-read direct RNA-sequencing from Oxford Nanopore to examine how METTL3 affects alternative splicing (AS) in two PCa cell lines. By dissecting genome-wide METTL3-regulated AS events, we noted that two PCa cell lines (representing two different PCa subtypes, androgen-sensitive or resistant) behave differently in exon skipping and intron retention events following METTL3 depletion, suggesting AS heterogeneity in PCa. Moreover, we revealed that METTL3-regulated AS is dependent on N6-methyladenosine (m6A) and distinct splicing factors. Analysis of the AS landscape also revealed cell type specific AS signatures for some genes (e.g., MKNK2) involved in key functions in PCa tumorigenesis. Finally, we also validated the clinical relevance of MKNK2 AS events in PCa patients and pointed to the possible regulatory mechanism related to m6A in the exon14a/b region and SRSF1. Overall, we characterize the role of METTL3 in regulating PCa-associated AS programs, expand the role of METTL3 in tumorigenesis, and suggest that MKNK2 AS events may serve as a new potential prognostic biomarker.

Sex-specific incidence of hepatitis B virus flares among Bcr-Abl tyrosine kinase inhibitor users in Taiwan.

BACKGROUND: The use of Bcr-Abl TKI was found to be associated with hepatitis B (HBV) flares, with a more profound risk observed in females. This study was conducted to characterize the clinical features of patients with HBV flare among Bcr-Abl TKI users, to estimate sex-specific incidence rates of HBV flare, and to evaluate potential cumulative effect of Bcr-Abl TKI. METHODS: Bcr-Abl TKI users with chronic HBV infection were identified from Taiwan's National Health Insurance database. The HBV flare cases were identified within the cohort. Incidence rates of HBV flare between men and women were assessed. Nested case-control analysis was used to evaluate the cumulative effect of Bcr-Abl TKI use on HBV flare. RESULTS: Among 415 patients with chronic HBV infection treated with Bcr-Abl TKI from 2005 through 2018, 45 flare cases (28 males and 17 females) were identified. Days between Bcr-Abl TKI initiation and HBV flare was 319 days in women compared to 610 days in men. 66.7% of the flares occurred during TKI therapy. Twelve of the 45 patients died, half of them died around 6 months after hepatitis B flare. Incidence rates of HBV flare were 2.34 and 3.33 per 100 person-years in males and females, respectively. Higher incidence was observed among patients with chronic myeloid leukemia. Cumulative effect of Bcr-Abl TKI on HBV flare was not observed. CONCLUSION: Approximately 10% of HBV carriers who used Bcr-Abl TKI experienced HBV flare in Taiwan. The risk was higher in women and among patients with chronic myeloid leukemia.

Glucose metabolic heterogeneity correlates with pathological features and improves survival stratification of resectable lung adenocarcinoma.

OBJECTIVE: We investigated whether glycolytic heterogeneity correlated with histopathology, and further stratified the survival outcomes pertaining to resectable lung adenocarcinoma. METHODS: We retrospectively analyzed the 18F-fluorodeoxyglucose positron emission tomography-derived entropy and histopathology from 128 patients who had undergone curative surgery for lung adenocarcinoma. Disease-free survival (DFS) and overall survival (OS) were analyzed using univariate and multivariate Cox regression models. Independent predictors were used to construct survival prediction models. RESULTS: Entropy significantly correlated with histopathology, including tumor grades, lympho-vascular invasion, and visceral pleural invasion. Furthermore, entropy was an independent predictor of unfavorable DFS (p = 0.031) and OS (p = 0.004), while pathological nodal metastasis independently predicted DFS (p = 0.009). Our entropy-based models outperformed the traditional staging system (c-index = 0.694 versus 0.636, p = 0.010 for DFS; c-index = 0.704 versus 0.630, p = 0.233 for OS). The models provided further survival stratification in subgroups comprising different tumor grades (DFS: HR = 2.065, 1.315, and 1.408 for grade 1-3, p = 0.004, 0.001, and 0.039, respectively; OS: HR = 25.557, 6.484, and 2.570, for grade 1-3, p = 0.006, < 0.001, and = 0.224, respectively). CONCLUSION: The glycolytic heterogeneity portrayed by entropy is associated with aggressive histopathological characteristics. The proposed entropy-based models may provide more sophisticated survival stratification in addition to histopathology and may enable personalized treatment strategies for resectable lung cancer.

Genome assembly and annotation of Periplaneta americana reveal a comprehensive cockroach allergen profile.

BACKGROUND: One of the most common cockroach types in urban areas, the American cockroach (Periplaneta americana), has been reported to impose an increased risk of allergies and asthma. Limited groups of allergens (Per a 1-13) have been identified in this species due to the lack of genome-related information. METHODS: To expand the allergen profile of P. americana, genomic, transcriptomic, and proteomic approaches were applied. With the support of a high-quality genome assembled using nanopore, Illumina, and Hi-C sequencing techniques, potential allergens were identified based on protein homology. Then, using enzyme-linked immunosorbent assay, selected allergens were tested in Thai patients allergic to P. americana. RESULTS: A chromosomal-level genome of P. americana (3.06 Gb) has been assembled with 94.6% BUSCO completeness, and its contiguity has been significantly improved (N50 = 151 Mb). A comprehensive allergen profile has been characterized, with seven novel groups of allergens, including enolase (Per a 14), cytochrome C (Per a 15), cofilin (Per a 16), alpha-tubulin (Per a 17), cyclophilin (Per a 18), porin3 (Per a 19), and peroxiredoxin-6 (Per a 20), showing IgE sensitivity in enzyme-linked immunosorbent assay. A new isoallergen of tropomyosin (Per a 7.02) and multiple potential isoallergens of Per a 5 were revealed using bioinformatics and proteomic approaches. Additionally, comparative analysis of P. americana with the closely related Blattodea species revealed the possibility of cross-reaction. CONCLUSION: The high-quality genome and proteome of P. americana are beneficial in studying cockroach allergens at the molecular level. Seven novel allergen groups and one isoallergen in Per a 7 were identified.

Mutational signatures representative transcriptomic perturbations in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a primary malignancy with increasing incidence and poor prognosis. Heterogeneity originating from genomic instability is one of the critical reasons of poor outcomes. However, the studies of underlying mechanisms and pathways affected by mutations are still not intelligible. Currently, integrative molecular-level studies using multiomics approaches enable comprehensive analysis for cancers, which is pivotal for personalized therapy and mortality reduction. In this study, genomic and transcriptomic data of HCC are obtained from The Cancer Genome Atlas (TCGA) to investigate the affected coding and non-coding RNAs, as well as their regulatory network due to certain mutational signatures of HCC. Different types of RNAs have their specific enriched biological functions in mutational signature-specific HCCs, upregulated coding RNAs are predominantly associated with lipid metabolism-related pathways, and downregulated coding RNAs are enriched in axonogenesis for tumor microenvironment generation. Additionally, differentially expressed miRNAs are inclined to concentrate in cancer-related signaling pathways. Some of these RNAs also serve as prognostic factors that help predict the survival outcome of HCCs with certain mutational signatures. Furthermore, deregulation of competing endogenous RNA (ceRNA) regulatory network is identified, which suggests a potential therapy via interference of miRNA activity for mutational signature-specific HCC. This study proposes a projection approach to reduce therapeutic complexity from genomic mutations to transcriptomic alterations. Through this method, we identify genes and pathways critical for mutational signature-specific HCC and further discover a series of prognostic markers indicating patient survival outcome.

Analysis of the close contact management mode and epidemiological characteristics of COVID-19 in Chengdu, China.

With the development of the novel coronavirus disease 2019 (COVID-19) epidemic and the increase in cases, as a potential source of infection, the risk of close contact has gradually increased. However, few studies have analyzed the tracking and management of cross-regional personnel. In this study, we hope to understand the effectiveness and feasibility of existing close contact management measures in Chengdu, so as to provide a reference for further prevention and control of the epidemic. The close contact management mode and epidemiological characteristics of 40,425 close contacts from January 22, 2020, to March 1, 2022, in Chengdu, China, were analyzed. The relationship with index cases was mainly co-passengers (57.58%) and relatives (7.20%), and the frequency of contact was mainly occasional contact (70.39%). A total of 400 (0.99%) close contacts were converted into cases, which were mainly found in the first and second nucleic acid tests (53.69%), and the contact mode was mainly by sharing transportation (63.82%). In terms of close contact management time, both the supposed ((11.93 ± 3.00) days vs. (11.92 ± 7.24) days) and actual ((13.74 ± 17.47) days vs. (12.60 ± 4.35) days) isolation times in Chengdu were longer than those of the outer cities (P < 0.001). For the local clustered epidemics in Chengdu, the relationship with indexed cases was mainly colleagues (12.70%). The tracing and management of close contacts is a two-way management measure that requires cooperation among departments. Enhancing existing monitoring and response capabilities can control the spread of the epidemic to a certain extent.

Comparative Genomics Reveals Insights into the Divergent Evolution of Astigmatic Mites and Household Pest Adaptations.

Highly diversified astigmatic mites comprise many medically important human household pests such as house dust mites causing ∼1-2% of all allergic diseases globally; however, their evolutionary origin and diverse lifestyles including reversible parasitism have not been illustrated at the genomic level, which hampers allergy prevention and our exploration of these household pests. Using six high-quality assembled and annotated genomes, this study not only refuted the monophyly of mites and ticks, but also thoroughly explored the divergence of Acariformes and the diversification of astigmatic mites. In monophyletic Acariformes, Prostigmata known as notorious plant pests first evolved, and then rapidly evolving Astigmata diverged from soil oribatid mites. Within astigmatic mites, a wide range of gene families rapidly expanded via tandem gene duplications, including ionotropic glutamate receptors, triacylglycerol lipases, serine proteases and UDP glucuronosyltransferases. Gene diversification after tandem duplications provides many genetic resources for adaptation to sensing environmental signals, digestion, and detoxification in rapidly changing household environments. Many gene decay events only occurred in the skin-burrowing parasitic mite Sarcoptes scabiei. Throughout the evolution of Acariformes, massive horizontal gene transfer events occurred in gene families such as UDP glucuronosyltransferases and several important fungal cell wall lytic enzymes, which enable detoxification and digestive functions and provide perfect drug targets for pest control. This comparative study sheds light on the divergent evolution and quick adaptation to human household environments of astigmatic mites and provides insights into the genetic adaptations and even control of human household pests.

A Dietitian-Led Vegan Program May Improve GlycA, and Other Novel and Traditional Cardiometabolic Risk Factors in Patients With Dyslipidemia: A Pilot Study.

Background: Systematic inflammation and lipid profiles are two major therapeutic targets for cardiovascular diseases. The effect of a nutritionally balanced vegan diet on systematic inflammation and lipoprotein subclass awaits further examination. Objective: To investigate the change in novel and traditional cardiometabolic risk factors before and after a dietitian-led vegan program, and to test the bioavailability of vitamin B12 in Taiwanese purple laver as part of a vegan diet. Design: A one-arm pilot intervention study. Participants/Setting: Nine patients with dyslipidemia participated in this 12-week vegan program. Main Outcome Measures: Nuclear Magnetic Resonance (NMR) detected GlycA signals (systematic inflammation) and lipoprotein subclass (atherogenicity); trimethylamine N-oxide (TMAO); and other cardiometabolic risk factors. Statistical Analyses Performed: Wilcoxon signed-rank test. Results: In this 12-week vegan intervention emphasizing whole foods, systematic inflammation improved as indicated by a reduction in GlycA (median: -23 µmol/L, p = 0.01). LDL-c (low-density lipoprotein cholesterol) (median -24 mg/dl, p = 0.04) and LDL-p (low-density lipoprotein particles) (median -75 nmol/L, p = 0.02) both decreased significantly. VLDL (very-low-density lipoprotein) and chylomicron particles showed a decreasing trend (-23.6 nmol/L, p = 0.05). Without caloric restriction, body mass index (BMI) (-0.7 kg/m2, p = 0.03), waist circumferences (-2.0 cm, p < 0.001), HbA1c (-0.2%, p = 0.02), and (HOMA-IR) homeostatic model assessment for insulin resistance (-0.7, p = 0.04) have all improved. The change in the TMAO and vitamin B12 status as measured by holo-transcobalamin appeared to depend on baseline diets, TMAO, and vitamin B12 status. Conclusions: A dietitian-led vegan program may improve systematic inflammation and other novel and traditional cardiometabolic risk factors in high-risk individuals.

Tumor glycolytic heterogeneity improves detection of regional nodal metastasis in patients with lung adenocarcinoma.

OBJECTIVE: The diagnostic performance of 18F-FDG PET for detecting regional lymph node metastasis in resectable lung cancer is variable, and its sensitivity for adenocarcinoma is even lower. We aimed to evaluate the value of 18F-FDG PET-derived features in predicting pathological lymph node metastasis in patients with lung adenocarcinoma. METHODS: We retrospectively analyzed pretreatment 18F-FDG PET-derived features of 126 lung adenocarcinoma patients who underwent curative surgery. A logistic regression model was used to analyze the association between study variables and pathological regional lymph node status obtained from the curative surgery. Furthermore, Cox regression analysis was used to test the effect of the study variables on survival outcomes, including disease-free survival (DFS) and overall survival (OS). RESULTS: The primary tumor entropy (OR = 1.7, p = 0.014) and visual interpretation of regional nodes via 18F-FDG PET (OR = 2.5, p = 0.026) independently predicted pathological regional lymph node metastasis. The areas under the receiver-operating-characteristic curves were 0.631, 0.671, and 0.711 for visual interpretation, primary tumor entropy, and their combination, respectively. Based on visual interpretation, a primary tumor entropy ≥ 3.0 improved the positive predictive value of positive visual interpretation from 51.2% to 63.0%, whereas an entropy < 3.0 improved the negative predictive value of negative visual interpretation from 75.3% to 82.6%. In cases with positive visual interpretation and low entropy, or negative visual interpretation and high entropy, the nodal metastasis rates were approximately 30%. In the survival analyses, the primary tumor entropy was also independently associated with DFS (HR = 2.7, p = 0.001) and OS (HR = 4.8, p = 0.001). CONCLUSIONS: Our preliminary results show that the primary tumor entropy may improve 18F-FDG PET visual interpretation in predicting pathological nodal metastasis in lung adenocarcinoma, and may also show a survival prognostic value. This versatile biomarker may facilitate tailored therapeutic strategies for patients with resectable lung adenocarcinoma.

Prognostic Value of Combing Primary Tumor and Nodal Glycolytic-Volumetric Parameters of 18F-FDG PET in Patients with Non-Small Cell Lung Cancer and Regional Lymph Node Metastasis.

We investigated whether the combination of primary tumor and nodal 18F-FDG PET parameters predict survival outcomes in patients with nodal metastatic non-small cell lung cancer (NSCLC) without distant metastasis. We retrospectively extracted pre-treatment 18F-FDG PET parameters from 89 nodal-positive NSCLC patients (stage IIB-IIIC). The Cox proportional hazard model was used to identify independent prognosticators of overall survival (OS) and progression-free survival (PFS). We devised survival stratification models based on the independent prognosticators and compared the model to the American Joint Committee on Cancer (AJCC) staging system using Harrell's concordance index (c-index). Our results demonstrated that total TLG (the combination of primary tumor and nodal total lesion glycolysis) and age were independent risk factors for unfavorable OS (p < 0.001 and p = 0.001) and PFS (both p < 0.001), while the Eastern Cooperative Oncology Group scale independently predicted poor OS (p = 0.022). Our models based on the independent prognosticators outperformed the AJCC staging system (c-index = 0.732 versus 0.544 for OS and c-index = 0.672 versus 0.521 for PFS, both p < 0.001). Our results indicate that incorporating total TLG with clinical factors may refine risk stratification in nodal metastatic NSCLC patients and may facilitate tailored therapeutic strategies in this patient group.

Association of Bcr-Abl Tyrosine Kinase Inhibitors With Hepatitis B Virus Reactivation Requiring Antiviral Treatment in Taiwan.

Importance: The US Food and Drug Administration (FDA) highlighted the potential risk of hepatitis B reactivation that was associated with Bcr-Abl tyrosine kinase inhibitor (TKI) treatment and has required updated product labels. Objective: To examine the association between hepatitis B flare and exposure to Bcr-Abl TKIs compared with non-Bcr-Abl TKIs. Design, Setting, and Participants: This nested case-control study included patients who entered a hepatitis B carrier cohort in Taiwan after January 1, 2005. Patients who received their first antiviral agents for hepatitis B flare for more than 28 days after the cohort entry date were included as case patients. For each case, a corresponding risk set was formed that included all eligible patients in the study cohort who had the same age (within 1 year), same sex, and were at risk of developing hepatitis B flare at the case date. As many as 10 control patients were randomly selected from the risk set for each case patient. TKIs were evaluated before the hepatitis B flare for case patients and before the corresponding index date for control patients. Data were collected from the Taiwan National Health Insurance research database from January 2000 to 2015. Data analysis was conducted from January to June 2019. Exposure: Use of Bcr-AbL TKIs. Main Outcomes and Measures: Conditional logistic regression was used to estimate the rate ratio for the association between hepatitis B flare and exposure to Bcr-Abl TKIs compared with non-Bcr-Abl TKIs. Results: Among 698 342 patients who carried incident hepatitis B virus, 66 702 patients with hepatitis B flare that required antiviral treatment (47 492 [71.2%] men; mean [SD] age at index date, 50.2 [13.8] years) were included as case patients, and 666 989 age and sex-matched patients (474 903 [71.2%] men; mean [SD] age, 50.2 [13.8] years) were included as control patients. Analysis revealed that Bcr-Abl TKI use during the previous 90 days was independently associated with a 56% higher risk of hepatitis B flare (adjusted rate ratio [aRR], 1.56; 95% CI, 1.11-2.20), and the aRR increased to 1.66 (95% CI, 1.20-2.28) for Bcr-Abl TKI use during the previous 365 days. Use of Bcr-AbL TKIs during the previous 60 days was associated with a significantly increased risk of flare among women (aRR, 3.20; 95% CI, 1.70-6.03) but not among men (aRR, 1.14; 95% CI, 0.72-1.81). Conclusions and Relevance: These findings suggest that sex-specific strategies may be needed to monitor for hepatitis B reactivation among patients receiving Bcr-Abl TKIs.

Biomimetic hydroxyapate/polydopamine composites with good biocompatibility and efficiency for uncontrolled bleeding.

Uncontrolled bleeding is thought to be the most deadly cause of pre-hospital, traffic, and military accidents death. However, the popular commercial hemostats can only realize the hemostasis of mild bleeding. Therefore, we developed polydopamine (PDA) composite materials (PMs), which applied hydroxyapatite as the parent body. The PMs were produced via lyophilization and functionalized with amino, phenol hydroxyls groups, which endowed hydrophobicity to materials. This ensured a high aggregation ability of blood cells to the PMs and they were tested to be as high as 300% compared with the negative control group. The clotting time was shortened to 79.7% compared with the usually used commercial hemostat (Celox) in the test of in vitro hemostasis. Through the results of PT and APTT tests, blood coagulation index test, and the analysis of intracellular Ca2+ activation, we further understood the mechanism of the hemostasis of the materials, which explained the low blood loss and quick coagulation time of the PM hemostats in detail. Besides, the low hemolysis and cytotoxicity of the PMs suggested the good biocompatibility of the hemostats, which was further proved by the regular morphology maintained by erythrocytes in the hemolysis tests. The study of nanoscale composites led the research for the methods of hemostasis.

Incorporating radiomic feature of pretreatment 18F-FDG PET improves survival stratification in patients with EGFR-mutated lung adenocarcinoma.

BACKGROUND: To investigate the survival prognostic value of the radiomic features of 18F-FDG PET in patients who had EGFR (epidermal growth factor receptor) mutated lung adenocarcinoma and received targeted TKI (tyrosine kinase inhibitor) treatment. METHODS: Fifty-one patients with stage III-IV lung adenocarcinoma and actionable EGFR mutation who received first-line TKI were retrospectively analyzed. All patients underwent pretreatment 18F-FDG PET/CT, and we calculated the PET-derived radiomic features. Cox proportional hazard model was used to examine the association between the radiomic features and the survival outcomes, including progression-free survival (PFS) and overall survival (OS). A score model was established according to the independent prognostic predictors and we compared this model to the TNM staging system using Harrell's concordance index (c-index). RESULTS: Forty-eight patients (94.1%) experienced disease progression and 41 patients (80.4%) died. Primary tumor SUV entropy > 5.36, and presence of pleural effusion were independently associated with worse OS (both p < 0.001) and PFS (p = 0.001, and 0.003, respectively). We used these two survival predictors to devise a scoring system (score 0-2). Patients with a score of 1 or 2 had a worse survival than those with a score of 0 (HR for OS: 3.6, p = 0.006 for score 1, and HR: 21.8, p < 0.001 for score 2; HR for PFS: 2.2, p = 0.027 for score 1 and HR: 8.8, p < 0.001 for score 2). Our scoring system surpassed the TNM staging system (c-index = 0.691 versus 0.574, p = 0.013 for OS, and c-index = 0.649 versus 0.517, p = 0.004 for PFS). CONCLUSIONS: In this preliminary study, combining PET radiomics with clinical risk factors may improve survival stratification in stage III-IV lung adenocarcinoma with actionable EFGR mutation. Our proposed scoring system may assist with optimization of individualized treatment strategies in these patients.

Genome-Wide Characterization of Host Transcriptional and Epigenetic Alterations During HIV Infection of T Lymphocytes.

Background and methods: Host genomic alterations are closely related to dysfunction of CD4+ T lymphocytes in the HIV-host interplay. However, the roles of aberrant DNA methylation and gene expression in the response to HIV infection are not fully understood. We investigated the genome-wide DNA methylation and transcriptomic profiles in two HIV-infected T lymphocyte cell lines using high-throughput sequencing. Results: Based on DNA methylation data, we identified 3,060 hypomethylated differentially methylated regions (DMRs) and 2,659 hypermethylated DMRs in HIV-infected cells. Transcription-factor-binding motifs were significantly associated with methylation alterations, suggesting that DNA methylation modulates gene expression by affecting the binding to transcription factors during HIV infection. In support of this hypothesis, genes with promoters overlapping with DMRs were enriched in the biological function related to transcription factor activities. Furthermore, the analysis of gene expression data identified 1,633 upregulated genes and 2,142 downregulated genes on average in HIV-infected cells. These differentially expressed genes (DEGs) were significantly enriched in apoptosis-related pathways. Our results suggest alternative splicing as an additional mechanism that may contribute to T-cell apoptosis during HIV infection. We also demonstrated a genome-scale correlation between DNA methylation and gene expression in HIV-infected cells. We identified 831 genes with alterations in both DNA methylation and gene expression, which were enriched in apoptosis. Our results were validated using various experimental methods. In addition, consistent with our in silico results, a luciferase assay showed that the activity of the PDX1 and SMAD3 promoters was significantly decreased in the presence of HIV proteins, indicating the potential of these genes as genetic markers of HIV infection. Conclusions: Our results suggest important roles for DNA methylation and gene expression regulation in T-cell apoptosis during HIV infection. We propose a list of novel genes related to these processes for further investigation. This study also provides a comprehensive characterization of changes occurring at the transcriptional and epigenetic levels in T cells in response to HIV infection.

Preoperative F-18 fluorocholine PET/CT for the detection of hyperfunctioning parathyroid glands in patients with secondary or tertiary hyperparathyroidism: comparison with Tc-99m sestamibi scan and neck ultrasound.

OBJECTIVES: Currently, neck ultrasound is the preferred preoperative imaging in patients with secondary/tertiary hyperparathyroidism, and the use of Tc-99m sestamibi scan is limited in these patients. We conducted this study to compare the diagnostic utilities of F-18 fluorocholine PET/CT, Tc-99m sestamibi scintigraphy, and neck ultrasound for localizing hyperfunctioning parathyroid glands in secondary/tertiary hyperparathyroidism. METHODS: We prospectively enrolled 30 dialysis patients with a diagnosis of secondary/tertiary hyperparathyroidism; of these, 27 participants underwent all three imaging modalities, including dual-phase F-18 fluorocholine PET/CT (PET acquired 5 and 60 min after tracer injection), dual-phase Tc-99 m sestamibi SPECT/CT, and neck ultrasound. All patients underwent parathyroidectomy after imaging. We compared the lesion-based sensitivity, specificity, and accuracy of the three image tools using histopathology as the reference. RESULTS: A total of 27 patients (107 lesions) underwent all three imaging modalities and entered the final analysis. The lesion-based sensitivities of F-18 fluorocholine PET/CT, Tc-99m sestamibi, and ultrasound were 86%, 55%, and 62%, respectively (both p < 0.001, when comparing F-18 fluorocholine PET/CT to Tc-99 m sestamibi scan and to ultrasound). F-18 fluorocholine PET/CT, Tc-99m sestamibi, and ultrasound had similar specificities of 93%, 80%, and 87%, respectively. The accuracy of F-18 fluorocholine PET/CT (87%) was significantly higher than that of Tc-99m sestamibi (59%) and ultrasound (65%) (both p < 0.001). F-18 fluorocholine PET/CT identified more hyperplastic glands than ultrasound in 52% (14/27) patients. The sensitivity of F-18 fluorocholine PET/CT reached 95% for hyperplastic parathyroid masses as low as 200 mg. CONCLUSIONS: F-18 fluorocholine PET/CT shows superior accuracy over the conventional imaging modalities in patients with secondary or tertiary hyperparathyroidism. The combination of F-18 fluorocholine PET/CT and neck ultrasound may enable better surgical planning in these patients. REGISTRATION IDENTIFICATION NUMBER: NCT04316845.

Continuous positive pressure therapy usage and incident stroke in patients with obstructive sleep apnea: A nationwide population-based cohort study.

INTRODUCTION: Continuous positive airway pressure (CPAP) is the main treatment for obstructive sleep apnea (OSA). To date, the link between CPAP usage and incident stroke has been inconsistent. OBJECTIVE: This nationwide population study is designed to examine the effect of CPAP on stroke incidence in OSA patients. METHODS: Using Taiwan's National Health Insurance Research Database (NHIRD), this study collected data from 4275 OSA patients diagnosed between 2000 and 2011 and divided them into two groups according to whether they received CPAP treatment. After matching baseline demographics and comorbidities, both cohorts contained 959 OSA patients and were followed to a newly diagnosed stroke or until the end of 2013. Cox regression analysis was performed to examine the incidence of stroke between patients with OSA receiving CPAP or no CPAP treatment. RESULTS: CPAP treatment for OSA patients predicted a lower incidence rate (3.41 vs 5.43 per 1000 person-years) and tended to protect against the development of stroke (hazard ratio (HR): 0.68, 95% confidence interval (95% CI): 0.38-1.23) compared to those without CPAP treatment, but the estimate was not statistically significant. Similar results were also observed by dividing stroke into ischemic (2.65 vs 4.30 per 1000 person-years; HR: 0.67, 95% CI: 0.35-1.31) or hemorrhagic origin (0.76 vs 1.12 per 1000 person-years; HR: 0.67, 95% CI: 0.19-2.40). CONCLUSIONS: It is possible that treatment with CPAP might be beneficial for protection against stroke, but this conclusion should be interpreted with caution. Future studies with satisfactory CPAP quality and duration are needed to validate this observation.

Vegetarian diet and incidence of total, ischemic, and hemorrhagic stroke in 2 cohorts in Taiwan.

OBJECTIVE: To determine how a vegetarian diet affects stroke incidence in 2 prospective cohorts and to explore whether the association is modified by dietary vitamin B12 intake. METHODS: Participants without stroke in the Tzu Chi Health Study (cohort 1, n = 5,050, recruited in 2007-2009) and the Tzu Chi Vegetarian Study (cohort 2, n = 8,302, recruited in 2005) were followed until the end of 2014. Diet was assessed through food frequency questionnaires in both cohorts at baseline. Stroke events and baseline comorbidities were identified through the National Health Insurance Research Database. A subgroup of 1,528 participants in cohort 1 were assessed for serum homocysteine, vitamin B12, and folate. Associations between vegetarian diet and stroke incidences were estimated by Cox regression with age as time scale, adjusted for sex, education, smoking, alcohol, physical activities, body mass index (only in cohort 1), hypertension, diabetes, dyslipidemia, and ischemic heart diseases. RESULTS: Vegetarians had lower serum vitamin B12 and higher folate and homocysteine than nonvegetarians. In cohort 1, 54 events occurred in 30,797 person-years follow-up. Vegetarians (vs nonvegetarians) experienced lower risk of ischemic stroke (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.08-0.88). In cohort 2, 121 events occurred in 76,797 person-years follow-up. Vegetarians (vs nonvegetarians) experienced lower risk of overall stroke (HR, 0.52; 95% CI, 0.33-0.82), ischemic stroke (HR, 0.41; 95% CI, 0.19-0.88), and hemorrhagic stroke (HR, 034; 95% CI, 0.12-1.00). Our explorative analysis showed that vitamin B12 intake may modify the association between vegetarian diet and overall stroke (p interaction = 0.046). CONCLUSION: Taiwanese vegetarian diet is associated with a lower risk of ischemic and hemorrhagic strokes.

Combining the radiomic features and traditional parameters of 18F-FDG PET with clinical profiles to improve prognostic stratification in patients with esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy and surgery.

OBJECTIVES: To investigate the role of the traditional and radiomic parameters of 18F-FDG PET for predicting the outcomes of patients with esophageal squamous cell carcinoma (SqCC). METHODS: Forty-four patients with primary esophageal SqCC who underwent neoadjuvant chemoradiotherapy (CCRT) followed by esophagectomy (tri-modality treatment) were retrospectively analyzed. All patients underwent 18F-FDG PET/CT before and after neoadjuvant CCRT. The radiomic features were calculated using the pre-treatment PET scan. Pre-treatment radiomic features and changes in the PET-derived traditional parameters after neoadjuvant CCRT were analyzed according to the pathological response to esophagectomy, disease-free survival (DFS), and overall survival (OS). We further developed a scoring system based on the independent survival prognosticators and compared our model to the traditional TNM staging system and surgical pathology. RESULTS: A pre-treatment primary tumor histogram entropy ≥ 3.69 predicts an unfavorable response to neoadjuvant CCRT (OR = 19.25, p = 0.009). An SUVmax reduction ratio ≤ 0.76, a pre-treatment primary tumor code similarity ≤ 0.0235, and incomplete pathological remission were independently associated with poor OS (p = 0.019, 0.033, and 0.038, respectively) and DFS (p = 0.049, 0.021, and 0.009, respectively). The three survival prognosticators were used to construct a scoring system (score 0-1, 2, and 3). Patients with a score of 2 or 3 had a significantly worse survival outcome than those with a score of 0-1 (HRs for OS: 3.58 for score 2, and 15.19 for score 3, p < 0.001; HRs for DFS: 1.39 for score 2 and 6.04 for score 3, p = 0.001).This survival prediction model was superior to the traditional TNM staging system (p < 0.001 versus p = 0.061 for OS, and p = 0.001 versus p = 0.027 for DFS) and the model based on surgical pathology (p < 0.001 versus p = 0.049 for OS, and p = 0.001 versus p = 0.022 for DFS). CONCLUSIONS: The 18F-FDG PET-derived radiomic parameter is useful for predicting the surgical pathological response in patients with esophageal SqCC treated with the tri-modality method. Using a combination of traditional and radiomic PET parameters with clinical profiles enables better stratification of patients into subgroups with various survival rates.

Borderline personality disorder is associated with an increased risk of sexually transmitted infections: A nationwide population-based cohort study in Taiwan.

BACKGROUND: Several features of borderline personality disorder (BPD) are likely to be associated with sexual health problems, such as unstable attachment, unstable sexual identity and sexual impulsivity. Since the issue of sex is not openly discussed in Taiwanese society, sexual health needs, including screening and prevention of sexually transmitted infections (STI), are often neglected in this population. OBJECTIVE: The study aims to determine whether BPD is associated with an increased risk of subsequent STI in Taiwan. METHODS: Overall 669 patients with BPD and 2676 controls matched by gender and age were enrolled between 2000 and 2012 and followed until the end of 2013 using Taiwan's National Health Insurance Research Database. During the follow-up period, participants who developed STI (human immunodeficiency virus, syphilis, genital warts, gonorrhoea, chlamydia and trichomoniasis) were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the STI incidence rate between patients with BPD and unaffected controls. RESULTS: Patients with BPD were predisposed to developing STI (HR: 4.17, 95% CI 1.62 to 10.8) after adjusting for demographic data and psychiatric comorbidities. The stratification analysis revealed a similar risk trend with BPD and subsequent STI in each gender and age group and was significant in the subgroups of male (HR: 11.3, 95% CI 2.97 to 42.7) and those aged 18-34 years (HR: 4.85, 95% CI 1.71 to 13.7). Also, the comorbidity stratification analysis revealed that, when the effect of comorbidities was excluded, patients with pure BPD significantly exhibited the risk association for subsequent STI after adjusting for all variables (HR: 4.24, 95% CI 1.25 to 14.4). CONCLUSION: Given the greater potential of BPD to be associated with an increased risk of STI, there should be direct implications for the development of targeted prevention interventions in Taiwan's mental health clinics.