Transcriptomic and genomic characteristics of intrahepatic metastases of primary liver cancer.

BACKGROUND: Patients with primary multifocal hepatocellular carcinoma (HCC) have a poor prognosis and often experience a high rate of treatment failure. Multifocal HCC is mainly caused by intrahepatic metastasis (IM), and though portal vein tumor thrombosis (PVTT) is considered a hallmark of IM, the molecular mechanism by which primary HCC cells invade the portal veins remains unclear. Therefore, it is necessary to recognize the early signs of metastasis of HCC to arrange better treatment for patients. RESULTS: To determine the differential molecular features between primary HCC with and without phenotype of metastasis, we used the CIBERSORTx software to deconvolute cell types from bulk RNA-Seq based on a single-cell transcriptomic dataset. According to the relative abundance of tumorigenic and metastatic hepatoma cells, VEGFA+ macrophages, effector memory T cells, and natural killer cells, HCC samples were divided into five groups: Pro-T, Mix, Pro-Meta, NKC, and MemT, and the transcriptomic and genomic features of the first three groups were analyzed. We found that the Pro-T group appeared to retain native hepatic metabolic activity, whereas the Pro-Meta group underwent dedifferentiation. Genes highly expressed in the group Pro-Meta often signify a worse outcome. CONCLUSIONS: The HCC cohort can be well-typed and prognosis predicted according to tumor microenvironment components. Primary hepatocellular carcinoma may have obtained corresponding molecular features before metastasis occurred.

An [18F]FDG PET/3D-ultrashort echo time MRI-based radiomics model established by machine learning facilitates preoperative assessment of lymph node status in non-small cell lung cancer.

OBJECTIVES: To develop an [18F]FDG PET/3D-UTE model based on clinical factors, three-dimensional ultrashort echo time (3D-UTE), and PET radiomics features via machine learning for the assessment of lymph node (LN) status in non-small cell lung cancer (NSCLC). METHODS: A total of 145 NSCLC patients (training, 101 cases; test, 44 cases) underwent whole-body [18F]FDG PET/CT and chest [18F]FDG PET/MRI were enrolled. Preoperative clinical factors and 3D-UTE, CT, and PET radiomics features were analyzed. The Mann-Whitney U test, LASSO regression, and SelectKBest were used for feature extraction. Five machine learning algorithms were used to establish prediction models, which were evaluated by the area under receiver-operator characteristic (ROC), DeLong test, calibration curves, and decision curve analysis (DCA). RESULTS: A prediction model based on random forest, consisting of four clinical factors, six 3D-UTE, and six PET radiomics features, was used as the final model for PET/3D-UTE. The AUCs of this model were 0.912 and 0.791 in the training and test sets, respectively, which not only showed different degrees of improvement over individual models such as clinical, 3D-UTE, and PET (AUC-training = 0.838, 0.834, and 0.828, AUC-test = 0.756, 0.745, and 0.768, respectively) but also achieved the similar diagnostic efficacy as the optimal PET/CT model (AUC-training = 0.890, AUC-test = 0.793). The calibration curves and DCA indicated good consistency (C-index, 0.912) and clinical utility of this model, respectively. CONCLUSION: The [18F]FDG PET/3D-UTE model based on clinical factors, 3D-UTE, and PET radiomics features using machine learning methods could noninvasively assess the LN status of NSCLC. CLINICAL RELEVANCE STATEMENT: A machine learning model of 18F-fluorodeoxyglucose positron emission tomography/ three-dimensional ultrashort echo time could noninvasively assess the lymph node status of non-small cell lung cancer, which provides a novel method with less radiation burden for clinical practice. KEY POINTS: • The 3D-UTE radiomics model using the PLS-DA classifier was significantly associated with LN status in NSCLC and has similar diagnostic performance as the clinical, CT, and PET models. • The [18F]FDG PET/3D-UTE model based on clinical factors, 3D-UTE, and PET radiomics features using the RF classifier could noninvasively assess the LN status of NSCLC and showed improved diagnostic performance compared to the clinical, 3D-UTE, and PET models. • In the assessment of LN status in NSCLC, the [18F]FDG PET/3D-UTE model has similar diagnostic efficacy as the [18F]FDG PET/CT model that incorporates clinical factors and CT and PET radiomics features.

Diagnostic performance of mpox virus (MPXV) real-time PCR assays: multicenter assessment and extended sensitivity analysis.

PURPOSE: To comprehensively investigate the diagnostic performance of routinely used assays in MPXV testing, the National Center of Clinical Laboratories in China conducted a nationwide external quality assessment (EQA) scheme and an evaluated nine assays used by ≥ 5 laboratories in the EQA. METHODS: MPXV virus-like particles with 2700, 900 and 300 copies/mL were distributed to 195 EQA laboratories. For extended analysis, triple-diluted samples from 9000 to 4.12 copies/mL were repeated 20 times using the assays employed by ≥ 5 laboratories. The diagnostic performance was assessed by analyzing EQA data and calculating the limits of detection (LODs). RESULTS: The performance was competent in 87.69% (171/195) of the participants and 87.94% (175/199) of the datasets. The positive percentage agreements (PPAs) were greater than 99% for samples at 2700 and 900 copies/mL, and 95.60% (761/796) for samples at 300 copies/mL. The calculated LODs for the two clades ranged from 228.44 to 924.31 copies/mL and were greater than the LODs specified by the respective kits. EasyDiagnosis had the lowest calculated LODs and showed superior performance in EQA, whereas BioGerm and Sansure, with higher calculated LODs, did not perform well in EQA. CONCLUSION: This study provides valuable information from the EQA data and evaluation of the diagnostic performance of MPXV detection assays. It also provided insights into reagent optimization and enabled prompt public health interventions for the outbreak.

Artificial Neural Network Analysis of Determinants of Tacrolimus Pharmacokinetics in Liver Transplant Recipients.

BACKGROUND: The efficacy and toxicity of tacrolimus are closely related to its trough blood concentrations. Identifying the influencing factors of pharmacokinetics of tacrolimus in the early postoperative period is conducive to the optimization of the individualized tacrolimus administration protocol and to help liver transplant (LT) recipients achieve the target blood concentrations. OBJECTIVE: This study aimed to develop an artificial neural network (ANN) for predicting the blood concentration of tacrolimus soon after liver transplantation and for identifying determinants of the concentration based on Shapley additive explanation (SHAP). METHODS: In this retrospective study, we enrolled 31 recipients who were first treated with liver transplantation from the Department of Liver Transplantation and Hepatic Surgery, the First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital) from November 2020 to May 2021. The basic information, biochemical indexes, use of concomitant drugs, and genetic factors of organ donors and recipients were used for the ANN model inputs, and the output was the steady-state trough concentration (C0) of tacrolimus after oral administration in LT recipients. The ANN model was established to predict C0 of tacrolimus, SHAP was applied to the trained model, and the SHAP value of each input was calculated to analyze quantitatively the influencing factors for the output C0. RESULTS: A back-propagation ANN model with 3 hidden layers was established using deep learning. The mean prediction error was 0.27 ± 0.75 ng/mL; mean absolute error, 0.60 ± 0.52 ng/mL; correlation coefficient between predicted and actual C0 values, 0.9677; and absolute prediction error of all blood concentrations obtained by the ANN model, ≤3.0 ng/mL. The results indicated that the following factors had the most significant effect on C0: age, daily drug dose, genotype at CYP3A5 polymorphism rs776746 in both recipient and donor, and concomitant use of caspofungin. The predicted C0 value of tacrolimus in LT recipients increased in a dose-dependent manner when the daily dose exceeded 3 mg, whereas it decreased with age when LT recipients were older than 48 years. The predicted C0 was higher when recipients and donors had the genotype CYP3A5*3*3 than when they had the genotype CYP3A5*1. The predicted C0 value also increased with the use of caspofungin or Wuzhi capsule. CONCLUSION AND RELEVANCE: The established ANN model can be used to predict the C0 value of tacrolimus in LT recipients with high accuracy and good predictive ability, serving as a reference for personalized treatment in the early stage after liver transplantation.

LncRNA FRMD6-AS1/miR-491-5p/USP13 pathway attenuated ferroptosis and contributed to liver fibrosis.

Liver fibrosis is an invertible pathophysiologic process featured by excessive accumulation of extracellular matrix (ECM) which injures liver cells and activates hepatic stellate cells (HSCs). Besides, inducing ferroptosis in activated HSCs can alleviate liver fibrosis. LncRNAs modulate ferroptosis in activated HSCs and ECM deposition in liver fibrosis. However, the role of lncRNA FRMD6-AS1 in liver fibrosis is not discovered. In this study, lncRNA FRMD6-AS1 was dramatically up-regulated in activated HSCs. Knockdown of FRMD6-AS1 markedly increased iron ion, ROS and MDA levels, decreased GSH level, SLC7A11 and GPX4 protein expressions in activated HSCs. In addition, HSCs activation markers α-SMA and COL1α1 expressions were up-regulated in activated HSCs; knockdown of FRMD6-AS1 markedly down-regulated α-SMA and COL1α1 expressions in HSCs. Besides, lncRNA FRMD6-AS1 could interact with miR-491-5p, and negatively modulate miR-491-5p expression. USP13 was a target of miR-491-5p, and could be negatively modulated by miR-491-5p. Moreover, FRMD6-AS1 knockdown increased iron ion and ROS levels, decreased SLC7A11 and GPX4 protein expressions, facilitated HSCs viability, and up-regulated α-SMA and COL1α1 expressions via miR-491-5p/USP13 pathway. Finally, FRMD6-AS1 knockdown restored liver tissue structure and abrogated fibrosis in livers in a CCL4 liver fibrosis mouse model. Hence, lncRNA FRMD6-AS1/miR-491-5p/USP13 pathway repressed ferroptosis, promoted ECM deposition and facilitated liver fibrosis in vitro and in vivo models.

A ratiometric fluorescence and colorimetry dual-signal sensing strategy based on o-phenylenediamine and AuNCs for determination of Cu2+ and glyphosate.

A ratiometric fluorescence sensing strategy has been developed for the determination of Cu2+ and glyphosate with high sensitivity and specificity based on OPD (o-phenylenediamine) and glutathione-stabilized gold nanoclusters (GSH-AuNCs). Water-soluble 1.75-nm size GSH-AuNCs with strong red fluorescence and maximum emission wavelength at 682 nm were synthesized using GSH as the template. OPD was oxidized by Cu2+, which produced the bright yellow fluorescence oxidation product 2,3-diaminophenazine (DAP) with a maximum fluorescence emission peak at 570 nm. When glyphosate existed in the system, the chelation between glyphosate and Cu2+ hindered the formation of DAP and reduced the fluorescence intensity of the system at the wavelength of 570 nm. Meanwhile, the fluorescence intensity at the wavelength of 682 nm remained basically stable. It exhibited a good linear relationship towards Cu2+ and glyphosate in water in the range 1.0-10 µM and 0.050-3.0 µg/mL with a detection limit of 0.547 µM and 0.0028 µg/mL, respectively. The method was also used for the semi-quantitative determination of Cu2+ and glyphosate in water by fluorescence color changes visually detected by the naked eyes in the range 1.0-10 µM and 0.30-3.0 µg/mL, respectively. The sensing strategy showed higher sensitivity, more obvious color changes, and better disturbance performance, satisfying with the detection demands of Cu2+ and glyphosate in environmental water samples. The study provides a reliable detection strategy in the environment safety fields.

[Research progress of traditional Chinese medicines as quorum sensing inhibitors in collaboration with antibiotics to inhibit drug-resistant bacteria].

Quorum sensing system regulates the expression of genes related to bacterial growth, metabolism and other behaviors by sensing bacterial density, and controls the unified action of the entire bacterial population. This mechanism can ensure the normal secretion of bacterial metabolites and the stability of the biofilm microenvironment, providing protection for the formation of biofilms and the normal growth and reproduction of bacteria. Traditional Chinese medicine, capable of quorum sensing inhibition, can inhibit the formation of bacterial biofilms, reduce bacterial resistance, and enhance the anti-infection ability of antibiotics when combined with antibiotics. In recent years, the combination of traditional Chinese and Western medicine in the treatment of drug-resistant bacterial infections has become a research hotspot. Starting with the associations between quorum sensing, biofilm and drug-resistant bacteria, this paper reviews the relevant studies about the combined application of traditional Chinese medicines as quorum sensing inhibitors with antibiotics in the treatment of drug-resistant bacteria. This review is expected to provide ideas for the development of new clinical treatment methods and novel anti-infection drugs.

Advanced root mean square propagation with the warm-up algorithm for fiber coupling.

Fiber coupling plays an important role in applications such as free-space optical communication (FSOC) and self-referencing interferometry. However, the coupling efficiency is often affected by turbulence and platform vibrations, which requires dynamic coupling with optimization algorithms. In this paper, to further mitigate the effects of sudden disturbances and to expand the effective range of fiber coupling systems, we propose a new method called the advanced root mean square propagation with warm-up (ARW) algorithm. By adaptively adjusting both the gain rate and the perturbation rate with warm-up operations, the ARW algorithm can achieve higher effective range and acceptable steady-state coupling efficiency simultaneously. Simulation and experimental results demonstrate that the proposed method requires only 36.4% of the iterations of the SPGD algorithm to deal with sudden disturbances. Moreover, the effective range of the ARW algorithm is 530.50µrad in the specific coupling platform, which is 20% higher than the effective range of SPGD.

Performance evaluation of SARS-CoV-2 antigen detection in the post-pandemic era: multi-laboratory assessment.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen detection is an indispensable tool for epidemic surveillance in the post-pandemic era. Faced with irregular performance, a comprehensive external quality assessment (EQA) scheme was conducted by the National Center for Clinical Laboratories (NCCL) to evaluate the analytical performance and status of SARS-CoV-2 antigen tests. METHODS: The EQA panel included ten lyophilized samples containing serial 5-fold dilutions of inactivated SARS-CoV-2-positive supernatants of the Omicron BA.1 and BA.5 strains and negative samples, which were classified into "validating" samples and "educational" samples. Data were analyzed according to qualitative results for each sample. RESULTS: A total of 339 laboratories in China participated in this EQA scheme, and 378 effective results were collected. All validating samples were correctly reported by 90.56 % (307/339) of the participants and 90.21 % (341/378) of the datasets. The positive percent agreement (PPA) was >99 % for samples with concentrations of 2 × 107 copies/mL but was 92.20 % (697/756) for 4 × 106 copies/mL and 25.26 % (382/1,512) for 8 × 105 copies/mL samples. Colloidal gold was the most frequently used (84.66 %, 320/378) but showed the lowest PPAs (57.11 %, 1,462/2,560) for positive samples compared with fluorescence immunochromatography (90 %, 36/40) and latex chromatography (79.01 %, 335/424). Among 11 assays used in more than 10 clinical laboratories, ACON showed a higher sensitivity than other assays. CONCLUSIONS: The EQA study can help to validate whether it's necessary to update antigen detection assays for manufacturers and provide participants with information about the performance of assays to take the first step toward routine post-market surveillance.

The impact of insomnia on anxiety and depression: a longitudinal study of non-clinical young Chinese adult males.

Insomnia, anxiety, and depression commonly co-occured and were closely related. Most of the prior studies were cross-sectional, with a poor ability to infer causality. Longitudinal study was needed to classify the relationships. The present study conducted a longitudinal study of non-clinical young Chinese males to investigate whether insomnia predicted the likelihood of future anxiety and depression, and vice versa. Convenient sampling method was applied, and 288 participants was recruited from Shanghai in October 2017 with Athens Insomnia Scale (AIS), Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). 120 of them were re-tested in June 2018. The drop-out rate was 58.33%. Correlation analyses and cross-lagged analysis showed that AIS global score was significantly positively related with scores of depression and anxiety at baseline and follow-up. Insomnia was a predictive factor of anxiety, but it can't predict depression. In sum, insomnia may be an important cause of anxiety, while no predictive relationship was found between insomnia and depression.

Coherent combining of a large-scale fiber laser array over 2.1†km in turbulence based on a beam conformal projection system.

We demonstrated a beam conformal projection system for coherent combining of large-scale lasers over 2.1 km in turbulence 20 m above the ground, using the basic modules of a 19-element fiber phased array combined with coarse pointing by a gimbal mount. After coarse pointing and aberration corrections, the metrics (reflected light) of the combined beams from a basic module were best increased by 13.4 times, suggesting that our system promises the great effect of coherent combining under long-distance turbulence. Moreover, we tentatively realized coherent combining of two basic modules (38 lasers), which is the largest number of elements in a fiber laser coherent beam combination outdoors, to the best of our knowledge, with the metrics of combined beams increased by about 29 times.

A Comparative Study of Amide Proton Transfer Weighted Imaging and Intravoxel Incoherent Motion MRI Techniques Versus (18) F-FDG PET to Distinguish Solitary Pulmonary Lesions and Their Subtypes.

BACKGROUND: Amide proton transfer weighted imaging (APTw), intravoxel incoherent motion (IVIM), and positron emission tomography (PET) imaging all have the potential to characterize solitary pulmonary lesions (SPLs). PURPOSE: To compare APTw and IVIM with PET imaging for distinguishing between benign and malignant SPLs and their subtypes. STUDY TYPE: Prospective. POPULATION: Ninety-five patients, 78 with malignant SPLs (including 48 with adenocarcinoma [AC] and 17 with squamous cell carcinoma [SCC]), and 17 with benign SPLs. FIELD STRENGTH/SEQUENCE: Fast spin-echo (FSE) T2WI, FSE APTw and echo-planar imaging IVIM, MR-base attenuation correction (MRAC), and PET imaging on a 3-T whole-body PET/MR system. ASSESSMENT: The magnetization transfer ratio asymmetry (MTRasym) at 3.5 ppm, diffusion coefficient (D), pseudo diffusion coefficient (D*), perfusion fraction (f), and the maximum standardized uptake value (SUVmax) were analyzed. STATISTICAL TESTS: Individual sample t-test, Delong test, Pearson's correlation analysis, and area under the receiver operating characteristic curve (AUC). P < 0.05 indicated statistical significance. RESULTS: The MTRasym and SUVmax were significantly higher, and D was significantly lower in the malignant group (3.3 ± 2.6 [%], 7.8 ± 5, and 1.2 ± 0.3 [×10-3 mm2 /second]) compared to the benign group (-0.3 ± 1.6 [%], 3.1 ± 3.8, and 1.6 ± 0.3 [×10-3 mm2 /second]). The MTRasym and D were significantly lower, and SUVmax was significantly higher in the SCC group (0.8 ± 1.0 [%], 1.0 ± 0.2 [×10-3 mm2 /second] than in the AC group (4.1 ± 2.6 [%], 1.3 ± 0.3 [×10-3 mm2 /second], 6.7 ± 4.6). Besides, the combination (AUC = 0.964) of these three methods showed higher diagnostic efficacy than any individual method (AUC = 0.917, 0.851, 0.82, respectively) in identifying malignant and benign SPLs. However, APTw showed better diagnostic efficacy than the combination of three methods or PET imaging alone in distinguishing SCC and AC groups (AUC = 0.934, 0.781, 0.725, respectively). DATA CONCLUSION: APTw, IVIM, and PET imaging are all effective methods to distinguish benign and malignant SPLs and their subtypes. APTw is potentially more capable than PET imaging of distinguishing lung SCC from AC. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Evaluation of Amide Proton Transfer-Weighted Imaging for Lung Cancer Subtype and Epidermal Growth Factor Receptor: A Comparative Study With Diffusion and Metabolic Parameters.

BACKGROUND: Lung cancer is one of the most devastating diseases worldwide, and it is meaningful to assess the subtype and epidermal growth factor receptor (EGFR) status in lung cancer noninvasively by imaging methods. PURPOSE: To differentiate noninvasively small cell lung cancer (SCLC) from nonsmall cell lung cancer (NSCLC), and EGFR mutation-type from wild-type NSCLC by comparing amide proton transfer-weighted imaging (APTWI), diffusion-weighted imaging (DWI), and 2-[18 F]-fluoro-2-deoxy-d-glucose positron emission tomography (18 F-FDG PET). STUDY TYPE: Prospective. POPULATION: A total of 99 patients with lung cancer. FIELD STRENGTH/SEQUENCE: APTWI and DWI at 18 F-FDG PET/MRI 3.0 T. ASSESSMENT: The apparent diffusion coefficient (ADC), magnetization transfer ratio asymmetry (MTRasym [3.5 ppm]), maximum standardized uptake value (SUVmax ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated and compared. STATISTICAL TESTS: Individual sample t-test, Mann-Whitney U test, Logistic regression, and P < 0.05 were considered statistically significant. RESULTS: In NSCLC, MTRasym (3.5 ppm), MTV, and TLG were significantly lower and ADC was significantly higher than in SCLC; MTRasym (3.5 ppm) was significantly higher and SUVmax , MTV, and TLG were significantly lower in EGFR mutation-type NSCLC than in EGFR wild-type NSCLC. In the identification of SCLC and NSCLC, MTRasym (3.5 ppm), ADC, and MTV were independent predictors, the AUCs of the combination of independent predictors, MTV, TLG, MTRasym (3.5 ppm), and ADC were 0.942, 0.875, 0.843, 0.814, and 0.687, respectively. In the identification of EGFR mutation-type and wild-type NSCLC, MTRasym (3.5 ppm) and MTV were independent predictors, the AUCs of the combination of independent predictors, TLG, MTV, MTRasym (3.5 ppm), and SUVmax were 0.919, 0.834, 0.813, 0.795, and 0.771, respectively. DATA CONCLUSION: In the noninvasive assessment of lung cancer subtype and EGFR status, APTWI has similar utility to diffusion and metabolic parameters. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Intercellular trafficking via plasmodesmata: molecular layers of complexity.

Plasmodesmata are intercellular pores connecting together most plant cells. These structures consist of a central constricted form of the endoplasmic reticulum, encircled by some cytoplasmic space, in turn delimited by the plasma membrane, itself ultimately surrounded by the cell wall. The presence and structure of plasmodesmata create multiple routes for intercellular trafficking of a large spectrum of molecules (encompassing RNAs, proteins, hormones and metabolites) and also enable local signalling events. Movement across plasmodesmata is finely controlled in order to balance processes requiring communication with those necessitating symplastic isolation. Here, we describe the identities and roles of the molecular components (specific sets of lipids, proteins and wall polysaccharides) that shape and define plasmodesmata structural and functional domains. We highlight the extensive and dynamic interactions that exist between the plasma/endoplasmic reticulum membranes, cytoplasm and cell wall domains, binding them together to effectively define plasmodesmata shapes and purposes.

Exploring undergraduate nursing students' experiences towards home-based learning as pedagogy during the COVID-19 pandemic: a descriptive qualitative exploration.

BACKGROUND: The global COVID-19 pandemic has led to the need for educators to explore online platforms in delivering lessons to students. Home-based learning is one of the most commonly-used teaching methods that allow learning to take place despite a physical separation between the students and the educators. METHODS: A descriptive qualitative approach was used to explore the experiences of nursing undergraduates when using home-based learning as a pedagogy during the COVID-19 pandemic. Data were collected from twenty-three nursing students (n = 14 in year one; n = 9 in year two) of their full-time pre-registration nursing program in a public-funded university in Singapore. Semi-structured interviews using an interview guide was conducted through Zoom-based video-conferencing from November 2020 to January 2021. The interview lasted between 45 and 65 min (median = 45 min). Data collection took place concurrently with thematic analysis through Braun and Clarke's six-step approach. This study was reported according to the Consolidated Criteria for Reporting Qualitative Research. RESULTS: Three main themes identified during the data analysis were: (1) challenges of home-based learning, where students detailed their experiences and difficulties encountered during the process; (2) the effectiveness of home-based learning, which explored the pedagogy's impact on the students' learning experience; and (3) students' motivation to learn, where the effects on student morale and motivation in partaking in learning tasks were discussed. CONCLUSIONS: Results from this study suggested that universities should incorporate more home-based learning opportunities as home-based learning to continue playing a crucial role in the foreseeable future. Universities should continue to incorporate more home-based learning opportunities into the existing nursing curriculaa in order to test their capacities and address technical challenges in online learning. Future studies should also consider incorporating other pedagogical strategies when conducting lessons online.

A Longitudinal Qualitative Analysis of the Way Peer Support Specialist Roles Change Over Time in a Psychiatric Hospital Setting in Asia.

The current study seeks to determine how peer support roles change as peer support specialists' positions within organizations and departments mature. We followed ten peer support specialists over the course of a year, interviewing them at three points, starting approximately three months after they began working as peer support specialists. We used an inductive process to analyze our data and followed guidelines on the structuring of longitudinal qualitative trajectories to divide the data into watershed moments. Our participants worked in a variety of departments in the hospital, and their service use experiences generally echo those of their service users. Participants appear to pass through four phases over the course of their employment as peers: early beginnings, establishing the role, role narrowing, and role sustainability. Services wishing to integrate new peers must be aware of the time required for integration. Having general job descriptions limited to specifying that peers are expected to use their lived experience to support current service users may lead to uncertainty amongst new and existing staff. Without role clarity, peers may struggle to find their place. Pairing new staff with mentors may limit this burden. As roles consolidate, boundaries may emerge. If these boundaries narrow the role of the PSS, they may no longer find the role appealing. They may then choose other caregiver roles with wider or different spheres of influence. Organizations may benefit by clearly indicating if they expect peer support positions to be static or transitionary.

Dynamics of Hepatitis E Virus (HEV) Antibodies and Development of a Multifactorial Model To Improve the Diagnosis of HEV Infection in Resource-Limited Settings.

Serological markers are important for the diagnosis of hepatitis E virus (HEV) infection. This study aims to compare the diagnostic performance of the anti-HEV IgM and the HEV antigen (Ag) assays and establish a multifactorial model to improve the diagnosis of current HEV infection when HEV RNA detection is not available. A total of 809 serum samples, including 325 anti-HEV IgM-positive and 484 anti-HEV IgM-negative samples, were tested for HEV RNA. The anti-HEV IgM assay had very high sensitivity (99.4%) but moderate accuracy (79.2%) and specificity (74.3%). By retrospective follow-up of 58 patients with sequential samples (n = 143) tested for anti-HEV antibodies, we found anti-HEV IgM remained positive for more than 10 months in some HEV-infected patients, when HEV RNA was already undetectable; thus, decision solely based on anti-HEV IgM may lead to misdiagnosis. In contrast, the HEV Ag assay had very high specificity (100%). However, the detection efficiency of HEV Ag greatly diminished when the HEV RNA level was low or the anti-HEV IgG level was high. By logistic regression, a model integrating anti-HEV IgM, alanine aminotransferase, and HEV Ag was proposed, and the cutoff value was determined based on the testing results of the 143 sequential samples. The model was further evaluated with 67 randomly selected IgM-positive samples from single-visit patients. Overall, the model outperformed the anti-HEV IgM or the HEV Ag assay in the diagnosis of current HEV infection (sensitivity/specificity/accuracy, 89.5%/95.2%/91.9%). The area under the receiver operating characteristics curve of the model was greater than 0.97.

The Effect of Therapeutic Alliance on Attitudes Toward Psychiatric Medications in Schizophrenia.

PURPOSE/BACKGROUND: The differential influence of therapeutic alliance with different health care professionals on patients' medication adherence has never been examined. METHODS/PROCEDURES: Ninety-five stable outpatients (91 patients with schizophrenia and 4 patients with schizoaffective disorder) were recruited. Individual, clinical, and medication factors were assessed, along with drug attitude (10-item Drug Attitude Inventory). Comparison on these factors was made between outpatients who identified psychiatrists as the health care professional most involved in their care, as compared with other health care professionals. FINDINGS/RESULTS: Older age, longer duration of illness, presence of medical comorbidities, lower levels of internalized stigma, higher levels of insight, higher levels of functioning, lesser severity of depressive symptoms, and positive symptoms were found to be significantly associated with greater levels of drug attitude (small to moderate associations). Only therapeutic alliance had a large correlation with drug attitude (ρ = 0.503, P < 0.001). The therapeutic alliance scores between the 2 health care professionals groups are not significantly different. However, participants who have identified psychiatrists as the health care professional that contributed the most to their recovery reported a significantly more positive attitude (µ = 6.18, SD = 3.42) toward psychiatric medication as compared with the other health care professionals group (µ = 3.11, SD = 5.32, P = 0.004). Only 2 factors, the Revised Helping Alliance Questionnaire (ß = 0.424, P < 0.001) and Personal and Social Performance scale (ß = 0.272, P = 0.006), were statistically significant predictors of drug attitude. IMPLICATIONS/CONCLUSIONS: Therapeutic alliance is found to be the lead factor associated with drug attitude in patients with schizophrenia. Identifying psychiatrists as the health care professional most involved in the patients' recovery can greatly increase patients' drug attitudes. Maintaining individuals' functioning also contributes to drug attitude.

Optical Fiber Bundle-Based High-Speed and Precise Micro-Scanning for Image High-Resolution Reconstruction.

We propose an imaging method based on optical fiber bundle combined with micro-scanning technique for improving image quality without complex image reconstruction algorithms. In the proposed method, a piezoelectric-ceramic-chip is used as the micro-displacement driver of the optical fiber bundle, which has the advantages of small volume, fast response speed and high precision. The corresponding displacement of the optical fiber bundle can be generated by precise voltage controlling. An optical fiber bundle with core/cladding diameter 4/80 µm and hexagonal arrangement is used to scan the 1951 USAF target. The scanning step is 1 µm, which is equivalent to the diffraction limit resolution of the optical system. The corresponding information is recorded at high speed through photo-detectors and a high-resolution image is obtained by image stitching processing. The minimum distinguishable stripe width of the proposed imaging technique with piezoelectric-ceramic-chip driven micro-scanning is approximately 2.1 µm, which is 1 time higher than that of direct imaging with a CCD camera whose pixel size is close to the fiber core size. The experimental results indicate that the optical fiber bundle combined with piezoelectric-ceramic-chip driven micro-scanning is a high-speed and high-precision technique for high-resolution imaging.

Pharmacokinetics of gallic acid and protocatechuic acid in humans after dosing with Relinqing (RLQ) and the potential for RLQ-perpetrated drug-drug interactions on organic anion transporter (OAT) 1/3.

CONTEXT: Relinqing granules (RLQ) are being used alone or in combination with antibacterial drugs to treat urological disorders. OBJECTIVE: This study investigates the pharmacokinetics of RLQ in humans and the potential for RLQ-perpetrated interactions on transporters. MATERIALS AND METHODS: Twelve healthy subjects (six women and six men) participated to compare single- and multiple-dose pharmacokinetics of RLQ. In the single-dose study, all 12 subjects received 8 g of RLQ orally. After a 7-d washout period, the subjects received 8 g of RLQ for seven consecutive days (t.i.d.) and then a single dose. Gallic acid (GA) and protocatechuic acid (PCA) in plasma and urine samples were analysed using LC-MS/MS. The transfected cells were used to study the inhibitory effect of GA (50-5000 µg/L) and PCA (10-1000 µg/L) on transporters OAT1, OAT3, OCT2, OATP1B1, P-gp and BCRP. RESULTS: GA and PCA were absorbed into the blood within 1 h after administration and rapidly eliminated with a half-life of less than 2 h. The mean peak concentrations of GA (102 and 176 µg/L) and PCA (4.54 and 7.58 µg/L) were lower in males than females, respectively. The 24 h urine recovery rates of GA and PCA were about 10% and 5%, respectively. The steady-state was reached in 7 d without accumulation. GA was a potent inhibitor of OAT1 (IC50 = 3.73 µM) and OAT3 (IC50 = 29.41 µM), but not OCT2, OATP1B1, P-gp or BCRP. DISCUSSION AND CONCLUSIONS: GA and PCA are recommended as PK-markers in RLQ-related pharmacokinetic and drug interaction studies. We should pay more attention to the potential for RLQ-perpetrated interactions on transporters.