Skeletal muscle involvement in systemic amyloidosis is often overlooked.

AIM: Systemic amyloidosis is a condition in which misfolded amyloid fibrils are deposited within tissues. Amyloid myopathy is a rare manifestation of systemic amyloidosis. However, whether skeletal muscle involvement is underestimated and whether such deposition guarantees clinical and pathological myopathic features remain to be investigated. METHODS: We retrospectively reviewed patients with systemic amyloidosis, in whom skeletal muscle biopsies were performed at our centre between January 2018 and June 2023. In total, 28 patients with suspected systemic amyloidosis were included. Among these, 21 presented with cardiomyopathy but lacked myopathic symptoms. The clinical and pathological data of these patients were further analysed. The amyloid type was confirmed by immunohistochemistry. RESULTS: Twenty-eight patients with suspected systemic amyloidosis underwent muscle biopsy. Amyloid deposition in the skeletal muscle was confirmed in 24 patients, including 22 with light-chain amyloidosis (AL) and two with transthyretin amyloidosis (ATTR). Among the 24 patients, seven presented with muscle weakness and decreased muscle strength (Group 1, symptomatic myopathy), whereas the remaining 17 exhibited normal muscle strength (Group 2, asymptomatic myopathy). Group 1 included four patients with AL-λ, one with AL-κ and two with ATTR. Group 2 included 15 patients with AL-λ and two patients with AL-κ. In Group 1, six patients exhibited neuropathy, whereas only one patient in Group 2 presented with subclinical neuropathy on nerve conduction studies. Amyloid deposition in the interstitium was the most obvious change, observed in all 24 patients. Neuropathic changes, including denervation atrophy and muscle fibre grouping, were also common. Except for type 2 fibre atrophy, the other myopathic changes were mild and nonspecific. No sarcolemmal disruption was observed. Immunohistochemical analysis revealed marked positivity for MAC and MHC1 expression in the regions with amyloid deposits. Clinicopathological analysis revealed no significant differences in the extent of muscular amyloid deposition between the two groups. Nevertheless, patients in Group 1 displayed more pronounced neurogenic atrophy on skeletal muscle biopsies. CONCLUSIONS: Our study indicates that amyloid deposition in skeletal muscle is commonly observed but rarely causes symptomatic myopathy in systemic amyloidosis.

Nebivolol hydrochloride and its impurities induce pseudo-allergic reactions via mast cell activation.

Nebivolol hydrochloride is a third-generation ß-blocker commonly used to treat cardiovascular diseases. However, it has been reported to induce allergic reactions in clinical use which deserves much attention. Therefore, this study focused on the ability of two isomers of nebivolol and chiral isomer impurities to induce allergic reactions. Our findings demonstrate that both nebivolol and two isomeric impurities can activate mast cell degranulation in vitro and show significant retention on Mas-related G-protein-coupled receptor X2 (MRGPRX2)-HEK293 cell membrane chromatography. These effects were further validated in vivo, where nebivolol and impurity IP-3 were observed to cause toe swelling and mast cell degranulation in mice. Molecular docking studies revealed interactions between these compounds and key amino acids of MRGPRX2, suggesting a mechanism for the induced allergic reactions. This work lays the foundation for improving the clinical safety of nebivolol.

Application of noninvasive sampling technique in mitochondrial genome intraspecific phylogeny of the endangered butterfly, Teinopalpus aureus (Lepidoptera: Papilionidae).

The butterfly genus of Teinopalpus, endemic to Asia, embodies a distinct species of mountain-dwelling butterflies with specific habitat requirements. These species are rare in the wild and hold high conservation and research value. Similar to other protected species, the genetic analysis of the rare Teinopalpus aureus poses challenges due to the complexity of sampling. In this study, we successfully extracted DNA and amplified mitochondrial genomic DNA from various noninvasive sources such as larval feces, larval exuviae, larval head capsules, pupal exuviaes, and filamentous gland secretions, all integral parts of butterfly metamorphosis. This was conducted as part of a research initiative focused on the artificial conservation of T. aureus population in Jinggang Shan Nature Reserve. Our findings illustrated the successful extraction of DNA from multiple noninvasive sources, achieved through modified DNA extraction methodologies. Although the DNA concentration obtained from noninvasive samples was lower than that from muscle tissues of newly dead larvae during rearing, all samples met the requirements for PCR amplification and sequencing, yielding complete circular sequences. These sequences are pivotal for both interspecific and intraspecific genetic relationship analysis. Our methods can be extended to other insects, especially scarce species.

Evolution pattern estimated by computed tomography perfusion post-thrombectomy predicts outcome in acute ischemic stroke.

OBJECTIVES: Computed tomography perfusion (CTP) and computed tomography angiography (CTA) have been recommended to select acute ischemic stroke (AIS) patients for endovascular thrombectomy (EVT) but are not widely used for post-treatment evaluation. We aimed to observe abnormalities in CTP and CTA before and after EVT and evaluate post-EVT CTP and CTA as potential tools for improving clinical outcome prediction. METHODS: Patients with AIS who underwent EVT and received CTP and CTA before and after EVT were retrospectively evaluated. The ischemic core was defined as the volume of relative cerebral blood flow <30% and hypoperfusion as the volume of Tmax >6 s. A reduction in hypoperfusion volume >90% between baseline and post-EVT CTP was defined as tissue optimal reperfusion (TOR). The 90-day modified Rankin scale was used to evaluate the clinical outcome. RESULTS: Eighty-three patients were included. Patients with an absent ischemic core or with TOR after EVT had a higher rate of modified Thrombolysis in Cerebral Ischemia score 2c-3 and recanalization of post-treatment vessel condition based on follow-up CTA. Multivariable logistic regression revealed that the baseline ischemic core volume (OR:0.934, p=0.009), TOR (OR:8.322, p=0.029) and immediate NIHSS score after EVT (OR:0.761, p=0.012) were factors significantly associated with good clinical outcome. Combining baseline ischemic core volume and TOR with immediate NIHSS score after EVT showed greatest performance for good outcome prediction after EVT(AUC=0.921). CONCLUSIONS: The addition of pretreatment and post-treatment CTP information to purely clinical NIHSS scores might help to improve the efficacy for good outcome prediction after EVT.

Nr4a1 promotes renal interstitial fibrosis by regulating the p38 MAPK phosphorylation.

BACKGROUND: Renal interstitial fibrosis (RIF) is a common pathway to end-stage renal disease regardless of the initial etiology. Currently, the molecular mechanisms for RIF remains not fully elucidated. Nuclear receptor subfamily 4 group A member 1(Nr4a1), a member of the NR4A subfamily of nuclear receptors, is a ligand-activated transcription factor. The role of Nr4a1 in RIF remains largely unknown. METHODS: In this study, we determined the role and action mechanism of Nr4a1 in RIF. We used unilateral ureteral obstruction (UUO) mice and transforming growth factor (TGF)-ß1-treated human renal proximal tubular epithelial cells (HK-2 cells) as in vivo and in vitro models of RIF. A specific Nr4a1 agonist Cytosporone B (Csn-B) was applied to activate Nr4a1 both in vivo and in vitro, and Nr4a1 small interfering RNA was applied in vitro. Renal pathological changes were evaluated by hematoxylin and eosin and Masson staining, and the expression of fibrotic proteins including fibronectin (Fn) and collagen-I (Col-I), and phosphorylated p38 MAPK was measure by immunohistochemical staining and western blot analysis. RESULTS: The results showed that Nr4a1 was upregulated in UUO mouse kidneys, and was positively correlated with the degree of interstitial kidney injury and the levels of fibrotic proteins. Csn-B treatment aggravated UUO-induced renal interstitial fibrosis, and induced p38 MAPK phosphorylation. In vitro, TGF-ß induced Nr4a1 expression, and Nr4a1 downregulation prevented TGF-ß1-induced expression of Fn and Col-I and the activation of p38 MAPK. Csn-B induced fibrotic proteins expression and p38 MAPK phosphorylation, and moreover Csn-B induced fibrotic proteins expression was abrogated by treatment with p38 MAPK inhibitor SB203580. We provided further evidence that Csn-B treatment promoted cytoplasmic accumulation of Nr4a1. CONCLUSION: The findings in the present study indicate that Nr4a1 promotes renal fibrosis potentially through activating p38 MAPK kinase.

Deep Learning for Head and Neck CT Angiography: Stenosis and Plaque Classification.

Background Studies have rarely investigated stenosis detection from head and neck CT angiography scans because accurate interpretation is time consuming and labor intensive. Purpose To develop an automated convolutional neural network-based method for accurate stenosis detection and plaque classification in head and neck CT angiography images and compare its performance with that of radiologists. Materials and Methods A deep learning (DL) algorithm was constructed and trained with use of head and neck CT angiography images that were collected retrospectively from four tertiary hospitals between March 2020 and July 2021. CT scans were partitioned into training, validation, and independent test sets at a ratio of 7:2:1. An independent test set of CT angiography scans was collected prospectively between October 2021 and December 2021 in one of the four tertiary centers. Stenosis grade categories were as follows: mild stenosis (<50%), moderate stenosis (50%-69%), severe stenosis (70%-99%), and occlusion (100%). The stenosis diagnosis and plaque classification of the algorithm were compared with the ground truth of consensus by two radiologists (with more than 10 years of experience). The performance of the models was analyzed in terms of accuracy, sensitivity, specificity, and areas under the receiver operating characteristic curve. Results There were 3266 patients (mean age ± SD, 62 years ± 12; 2096 men) evaluated. The consistency between radiologists and the DL-assisted algorithm on plaque classification was 85.6% (320 of 374 cases [95% CI: 83.2, 88.6]) on a per-vessel basis. Moreover, the artificial intelligence model assisted in visual assessment, such as increasing confidence in the degree of stenosis. This reduced the time needed for diagnosis and report writing of radiologists from 28.8 minutes ± 5.6 to 12.4 minutes ± 2.0 (P < .001). Conclusion A deep learning algorithm for head and neck CT angiography interpretation accurately determined vessel stenosis and plaque classification and had equivalent diagnostic performance when compared with experienced radiologists. © RSNA, 2023 Supplemental material is available for this article.

Effect of APOE ε4 genotype on amyloid-ß, glucose metabolism, and gray matter volume in cognitively normal individuals and amnestic mild cognitive impairment.

BACKGROUND AND PURPOSE: The presence of apolipoprotein E ε4 (APOE ε4) is associated with an increased risk of developing Alzheimer disease (AD). The aim of this study was to assess the effects of APOE ε4 on amyloid-ß (Aß) pathology, glucose metabolism, and gray matter (GM) volume and their longitudinal changes in healthy control (HC) and amnestic mild cognitive impairment (aMCI). METHODS: We included 50 HCs and 109 aMCI patients from the Alzheimer's Disease Neuroimaging Initiative phase 2/GO based on availability of baseline T1-weighted magnetic resonance imaging, 18 F-florbetapir positron emission tomography (PET), and 18 F-fluorodeoxyglucose (FDG) PET. Of these, 35 HCs and 67 aMCI patients who underwent 24-month scans were included for follow-up study. RESULTS: Voxelwise analysis revealed that APOE ε4 carriers exhibited greater baseline Aß deposition than APOE ε4 noncarriers in both diagnostic groups. However, there was no significant difference between APOE ε4 noncarriers and APOE ε4 carriers in terms of 18 F-FDG PET standardized uptake value ratio and GM volume. Region of interest-based analysis showed statistically significant greater Aß deposition in APOE ε4 carriers than APOE ε4 noncarriers only in aMCI patients. Furthermore, APOE ε4 carriers generally exhibited a greater magnitude and spatial extent of longitudinal changes in Aß deposition than APOE ε4 noncarriers in both diagnostic groups. CONCLUSIONS: Our findings suggest a differential effect of APOE ε4 on Aß pathology, glucose metabolism, and GM volume. Studying APOE ε4-related brain changes with neuroimaging biomarkers in preclinical AD offers an opportunity to further our understanding of the pathophysiology of AD at an early stage.

Translating and Adapting the DISCERN Instrument Into a Simplified Chinese Version and Validating Its Reliability: Development and Usability Study.

BACKGROUND: There is a wide variation in the quality of information available to patients on the treatment of the diseases afflicting them. To help patients find clear and accessible information, many scales have been designed to evaluate the quality of health information, including the Patient Education Materials Assessment Tool; the Suitability Assessment of Materials for evaluation of health-related information for adults; and DISCERN, an instrument for judging the quality of written consumer health information on treatment choices. These instruments are primarily in English. Few of them have been translated and adapted into simplified Chinese tools for health information assessment in China. OBJECTIVE: This study aimed to translate and adapt DISCERN into the first simplified Chinese version and validate the psychometric properties of this newly developed scale for judging the quality of patient-oriented health information on treatment choices. METHODS: First, we translated DISCERN into simplified Chinese using rigorous guidelines for translation and validation studies. We tested the translation equivalence and measured the content validity index. We then presented the simplified Chinese instrument to 3 health educators and asked them to use it to assess the quality of 15 lung cancer-related materials. We calculated the Cohen κ coefficient and Cronbach α for all items and for the entire scale to determine the reliability of the new tool. RESULTS: We decided on the simplified Chinese version of the DISCERN instrument (C-DISCERN) after resolving all problems in translation, adaptation, and content validation. The C-DISCERN was valid and reliable: the content validity index was 0.98 (47/48, 98% of the items) for clarity and 0.94 (45/48, 94% of the items) for relevance, the Cronbach α for internal consistency was .93 (95% CI 0.699-1.428) for the whole translated scale, and the Cohen κ coefficient for internal consistency was 0.53 (95% CI 0.417-0.698). CONCLUSIONS: C-DISCERN is the first simplified Chinese version of the DISCERN instrument. Its validity and reliability have been attested to assess the quality of patient-targeted information for treatment choices.

The Chinese Version of the Patient Education Materials Assessment Tool for Printable Materials: Translation, Adaptation, and Validation Study.

BACKGROUND: Providing people with understandable and actionable health information can considerably promote healthy behaviors and outcomes. To this end, some valid and reliable scales assessing the patient-friendliness of health education materials, like the PEMAT-P (Patient Education Materials Assessment Tool for printable materials), have been well developed in English-speaking countries. However, the English version of the PEMAT-P has not been translated and adapted into simplified Chinese and validated in mainland China. OBJECTIVE: This study sought to translate the PEMAT-P tool into a simplified Chinese (Mandarin) version (C-PEMAT-P, a Chinese version of the Patient Education Materials Assessment Tool for printable materials) and verify its validity and reliability for assessing the comprehensibility and actionability of health education resources written in simplified Chinese. As a result, the validated C-PEMAT-P could be used to guide health researchers and educators to design more comprehensible and actionable materials for more tailored and targeted health education and interventions. METHODS: We translated the PEMAT-P into simplified Chinese in the following three steps: (1) forward-translating the PEMAT-P into simplified Chinese, (2) back-translating the simplified Chinese version into English, and (3) testing translation equivalence linguistically and culturally by examining the original English version of the PEMAT-P and the back-translated English version of the tool. Any discrepancies between the original English tool and the back-translated English tool were resolved through a panel discussion among the research team of all authors to produce a revised forward-translated Chinese version (C-PEMAT-P). We then evaluated the clarity of construction and wording as well as the content relevance of the C-PEMAT-P using a 4-point ordinal scale to determine its content validity. After that, 2 native Chinese speakers (health educators) used the C-PEMAT-P to rate 15 health education handouts concerning air pollution and health to validate their reliability. We calculated the Cohen coefficient and Cronbach α to determine the interrater agreement and internal consistency of the C-PEMAT-P, respectively. RESULTS: We finalized the translated Chinese tool after discussing the differences between the 2 English versions (original and back-translated) of the PEMAT-P, producing the final Chinese version of the PEMAT-P (C-PEMAT-P). The content validity index of the C-PEMAT-P version was 0.969, the Cohen coefficient for the interrater scoring agreement was 0.928, and the Cronbach α for internal consistency was .897. These values indicated the high validity and reliability of the C-PEMAT-P. CONCLUSIONS: The C-PEMAT-P has been proven valid and reliable. It is the first Chinese scale for assessing the comprehensibility and actionability of Chinese health education materials. It can be used as an assessment tool to evaluate health education materials currently available and a guide to help health researchers and educators design more comprehensible and actionable materials for more tailored and targeted health education and interventions.

Assessing Patients' Critical Health Literacy and Identifying Associated Factors: Cross-sectional Study.

BACKGROUND: Previous studies have revealed that functional health literacy plays a less important role than communicative and critical health literacy (CRHL) and that communicative literacy and CRHL contribute more to better patient self-management. Although improving health literacy has been identified as an approach to fostering community involvement and empowerment, CRHL may be regarded as the neglected domain of health literacy, rarely achieving any focus or interventions that claim to be working toward this outcome. Considering this research background, close scholarly attention needs to be paid to CRHL and its associated factors. OBJECTIVE: This study aimed to assess CRHL and identify essential factors closely associated with the status of CRHL among Chinese patients and to provide some implications for clinical practice, health education, medical research, and public health policy making. METHODS: We conducted this cross-sectional study, which lasted from April 8, 2022, to September 23, 2022, following the steps below. We first designed a 4-section survey questionnaire and then recruited Mandarin Chinese-speaking patients from Qilu Hospital of Shandong University, China, using randomized sampling. Subsequently, we administered the questionnaire via wenjuanxing, the most popular web-based survey platform in China, between July 20, 2022, and August 19, 2022. Finally, we used latent class modeling to analyze the valid data collected to classify the patient participants and identify the factors potentially associated with different CRHL levels. RESULTS: All data in the 588 returned questionnaires were valid. On the basis of the collected data, we classified the patient participants into 3 latent classes of limited, moderate, and adequate CRHL and identified 4 factors associated with limited CRHL, including middle and old age, male sex, lower educational attainment, and low internal drive to maintain one's health. CONCLUSIONS: Using latent class modeling, we identified 3 classes of CRHL and 4 factors associated with limited CRHL among the Chinese study participants. These literacy classes and the predicting factors ascertained in this study can provide some implications for clinical practice, health education, medical research, and health policy making.

Increased progranulin as an independent predictive biomarker for poor prognosis in sepsis.

BACKGROUND: Recently, many diagnostic biomarkers were reported, but each had its own limitation. However, there is a need for an effective sensitivity and specificity of biomarker in diagnosis and prognosis of sepsis. In this context, progranulin (PGRN), at elevated levels, has been associated with poor prognosis in infectious diseases. Moreover, increased PGRN levels were seen in septic mice. As the prognostic value of PGRN in humans is unclear, we aimed to identify the predictive value of serum PGRN for the prognosis of sepsis. METHODS: A total of 128 participants with sepsis and 58 healthy controls were recruited in this study. The levels of serum PGRN were detected by enzyme-linked immunosorbent assay. According to the outcomes, patients were divided into survival and non-survival groups. RESULTS: Serum PGRN levels had upregulated in patients with sepsis compared with those in healthy controls (P < 0.001) as well as in non­survivors compared with those in survivors (P < 0.001). Furthermore, serum PGRN levels exhibited positive correlation with hypersensitive C-reactive protein, procalcitonin, sepsis­related organ failure assessment (SOFA) scores, and acute physiology and chronic health evaluation II (APACHE II) scores. PGRN had a higher predictive effect, especially the 28-day in-hospital mortality (p < 0.001), when using it with SOFA or APACHE II scores. Cox proportional regression analysis showed that PGRN was an independent predictor for 28-day mortality risk in sepsis. CONCLUSIONS: PGRN, as a biomarker of sepsis, could improve the prognostic power of traditional parameters. This study is the first to report the clinical significance of PGRN levels in terms of the severity and prognosis of sepsis.

MGMT promoter methylation status shows no effect on [18F]FET uptake and CBF in gliomas: a stereotactic image-based histological validation study.

OBJECTIVES: To investigate the effects of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status of gliomas on O-(2-18F-fluoroethyl)-L-tyrosine ([18F]FET) uptake and cerebral blood flow (CBF) of arterial spin labeling (ASL), evaluated by hybrid PET/MR. Stereotactic biopsy was used to validate the findings. METHODS: A set of whole tumor and reference volumes of interest (VOIs) based on PET/FLAIR imaging were delineated and transferred to the corresponding [18F]FET PET and CBF maps in 57 patients with newly diagnosed gliomas. The mean and max tumor-to-brain ratio (TBR) and normalized CBF (nCBF) were calculated. The predictive efficacy of [18F]FET PET and CBF in determining MGMT promoter methylation status of glioma were evaluated by whole tumor analysis and stereotactic biopsy. The correlation between PET/MR parameters and MGMT promoter methylation were analyzed using histological specimens acquired from multiple stereotactic biopsies. RESULTS: Based on the analysis of whole tumor volume and biopsy site, TBRmean, TBRmax, nCBFmean, and nCBFmax showed no statistically significant differences between gliomas with and without MGMT promoter methylation (all p > 0.05). Furthermore, stereotactic biopsy demonstrated that TBRmean, TBRmax, nCBFmean, and nCBFmax showed no correlation with MGMT promoter methylation (r = -0.117, p = 0.579; r = -0.161, p = 0.443; r = -0.271, p = 0.191; r = -0.300, p = 0.145; respectively). CONCLUSIONS: MGMT promoter methylation status shows no effect on [18F]FET uptake and CBF of ASL in gliomas. Stereotactic biopsy validates it and further reveals there is no correlation of [18F]FET PET uptake and CBF with the percentages of MGMT promoter methylation. KEY POINTS: • Based on whole tumor VOI assessment, MGMT promoter methylation status shows no effect on [18F]FET uptake and CBF of ASL in gliomas. • For WHO grade IV glioblastomas, [18F]FET PET and ASL parameters based on hybrid PET/MR fail to predict the MGMT promoter methylation status. • Stereotactic image-based histology reveals that there is no correlation of [18F]FET PET uptake and CBF with the status and percentages of MGMT promoter methylation in gliomas.

Engineered nanomedicines block the PD-1/PD-L1 axis for potentiated cancer immunotherapy.

Immunotherapy, in particular immune checkpoint blockade (ICB) therapy targeting the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis, has remarkably revolutionized cancer treatment in the clinic. Anti-PD-1/PD-L1 therapy is designed to restore the antitumor response of cytotoxic T cells (CTLs) by blocking the interaction between PD-L1 on tumour cells and PD-1 on CTLs. Nevertheless, current anti-PD-1/PD-L1 therapy suffers from poor therapeutic outcomes in a large variety of solid tumours due to insufficient tumour specificity, severe cytotoxic effects, and the occurrence of immune resistance. In recent years, nanosized drug delivery systems (NDDSs), endowed with highly efficient tumour targeting and versatility for combination therapy, have paved a new avenue for cancer immunotherapy. In this review article, we summarized the recent advances in NDDSs for anti-PD-1/PD-L1 therapy. We then discussed the challenges and further provided perspectives to promote the clinical application of NDDS-based anti-PD-1/PD-L1 therapy.

Prosurvival kinase PIM2 is a therapeutic target for eradication of chronic myeloid leukemia stem cells.

A major obstacle to curing chronic myeloid leukemia (CML) is the intrinsic resistance of CML stem cells (CMLSCs) to the drug imatinib mesylate (IM). Prosurvival genes that are preferentially expressed in CMLSCs compared with normal hematopoietic stem cells (HSCs) represent potential therapeutic targets for selectively eradicating CMLSCs. However, the discovery of such preferentially expressed genes has been hampered by the inability to completely separate CMLSCs from HSCs, which display a very similar set of surface markers. To overcome this challenge, and to minimize confounding effects of individual differences in gene expression profiles, we performed single-cell RNA-seq on CMLSCs and HSCs that were isolated from the same patient and distinguished based on the presence or absence of BCR-ABL. Among genes preferentially expressed in CMLSCs is PIM2, which encodes a prosurvival serine-threonine kinase that phosphorylates and inhibits the proapoptotic protein BAD. We show that IM resistance of CMLSCs is due, at least in part, to maintenance of BAD phosphorylation by PIM2. We find that in CMLSCs, PIM2 expression is promoted by both a BCR-ABL-dependent (IM-sensitive) STAT5-mediated pathway and a BCR-ABL-independent (IM-resistant) STAT4-mediated pathway. Combined treatment with IM and a PIM inhibitor synergistically increases apoptosis of CMLSCs, suppresses colony formation, and significantly prolongs survival in a mouse CML model, with a negligible effect on HSCs. Our results reveal a therapeutically targetable mechanism of IM resistance in CMLSCs. The experimental approach that we describe can be generally applied to other malignancies that harbor oncogenic fusion proteins or other characteristic genetic markers.

Language Use in Conversational Agent-Based Health Communication: Systematic Review.

BACKGROUND: Given the growing significance of conversational agents (CAs), researchers have conducted a plethora of relevant studies on various technology- and usability-oriented issues. However, few investigations focus on language use in CA-based health communication to examine its influence on the user perception of CAs and their role in delivering health care services. OBJECTIVE: This review aims to present the language use of CAs in health care to identify the achievements made and breakthroughs to be realized to inform researchers and more specifically CA designers. METHODS: This review was conducted by following the protocols of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 statement. We first designed the search strategy according to the research aim and then performed the keyword searches in PubMed and ProQuest databases for retrieving relevant publications (n=179). Subsequently, 3 researchers screened and reviewed the publications independently to select studies meeting the predefined selection criteria. Finally, we synthesized and analyzed the eligible articles (N=11) through thematic synthesis. RESULTS: Among the 11 included publications, 6 deal exclusively with the language use of the CAs studied, and the remaining 5 are only partly related to this topic. The language use of the CAs in these studies can be roughly classified into six themes: (1) personal pronouns, (2) responses to health and lifestyle prompts, (3) strategic wording and rich linguistic resources, (4) a 3-staged conversation framework, (5) human-like well-manipulated conversations, and (6) symbols and images coupled with phrases. These derived themes effectively engaged users in health communication. Meanwhile, we identified substantial room for improvement based on the inconsistent responses of some CAs and their inability to present large volumes of information on safety-critical health and lifestyle prompts. CONCLUSIONS: This is the first systematic review of language use in CA-based health communication. The results and limitations identified in the 11 included papers can give fresh insights into the design and development, popularization, and research of CA applications. This review can provide practical implications for incorporating positive language use into the design of health CAs and improving their effective language output in health communication. In this way, upgraded CAs will be more capable of handling various health problems particularly in the context of nationwide and even worldwide public health crises.

First report of Colletotrichum fioriniae causing leaf spot on Schima superba in the world.

Schima superba Gardn. et Champ. is a subtropical evergreen tree species naturally distributed mainly in China, Japan, and Vietnam. It is primarily planted for its timber and urban landscaping in China (Ni, 1996). In September 2018, leaves necrotic spots were observed on S. superba in Jiangxi Forest Breeding Center (28°57'19.52" N, 115°39'21.32" E), Jiangxi Province, China. The disease incidence was about 30%. Initially, spots were circular to semicircular, grayish-brown in the center with dark brown margin, then expanded and eventually collapsed into sunken necrotic lesions. To identify the agent, diseased leaves were collected randomly. Pieces (5 × 5 mm) from the lesion borders were surfaced sterilized in 70% ethanol (30 s), 3% NaOCl (60 s), and rinsed 3 times in sterile water. These pieces were put on potato dextrose agar (PDA) and cultured at 25 °C. Pure cultures were obtained by monosporic isolation, and 3 isolates (MH-1, MH-2, MH-3) were used for morphological studies and phylogenetic analyses. On PDA, colonies were initially white, cottony, then became pinkish to deep-pink at the center and pink on the reverse. Conidia were fusiform with acute ends, smooth-walled, hyaline, 13.7-18.5 × 4.6-6.1 µm (16.4 ± 1.3× 5.3 ± 0.6 µm, n = 100). Conidiophores were colorless to pale brown, smooth, septate. Conidiogenous cells were colorless to pale brown, smooth, cylindrical to ampulliform. The morphological characteristics fit the descriptions of Colletotrichum acutatum J. H. Simmonds sensu lato (Damm et al., 2012). For accurate identification, genomic DNA of 3 isolates was extracted, and the internal transcribed spacer (ITS), actin (ACT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta-tubulin 2 (TUB2), and chitin synthase (CHS-1) were amplified and sequenced using the corresponding primers (Weir et al., 2012). The sequences were deposited in GenBank (ITS: MZ325946, MZ325947, MW584318; ACT: MZ399375, MZ419566, MW661171; CHS-1: MZ399376, MZ419567, MW661172; MZ399377, GAPDH: MZ419568, MW661173; TUB2: MZ399378, MZ419569, MW661174). Five loci were concatenated, and the aligned sequences (1528bp) were 99.89% homologous to ex-type C. fioriniae (Marcelino & Gouli) R. G. Shivas & Y. P. Tan CBS128517. Phylogenetic analysis using the maximum likelihood showed that 3 isolates were clustered in C. fioriniae clade with 100% bootstrap support. Based on the multi-locus phylogeny and morphology, 3 isolates were identified as C. fioriniae. Pathogenicity tests were performed on 36 seedlings of S. superba (2-year-old). The leaves were wounded slightly and inoculated with a drop of spore suspension (106 conidia/mL). The sterile water was used as controls. All the tested leaves were covered with black plastic bags to keep them moist for 2 days. All seedlings were placed in the greenhouse (25 °C, 12 h light/dark) for 10 days, and all inoculated leaves had typical symptoms. The controls were asymptomatic. The same fungus was reisolated from the lesions, fulfilling Koch's postulates. Colletotrichum fioriniae was described as a new species from the C. acutatum s. l. (Shivas et al., 2009), and it was an important plant pathogen, such as Pyrus spp. (Pavlovic et al., 2019), Morus alba L. (Xue et al., 2019), and so on. This is the first report of the newly emerging disease of S. superba caused by C. fioriniae in the world, and its potential threat should be evaluated in the future. This study provided crucial information for epidemiologic studies and appropriate control strategies.

Brain Abnormalities in Pontine Infarction: A Longitudinal Diffusion Tensor Imaging and Functional Magnetic Resonance Imaging study.

OBJECTIVES: The aim of this study was to make a reasonable and accurate assessment of the prognosis of patients with pontine infarction. We assessed the changes in structure and function in the whole brain after pontine infarction from the acute to chronic phase using diffustion tensor imaging and functional magnetic resonance imaging. MATERIALS AND METHODS: Sixteen individuals with a recent pontine infarction and sixteen healthy controls were recruited and underwent 3.0T DTI, resting-state fMRI and upper extremity Fugl-Myer (UE-FM) functional evaluation at five time points: within one week (T1), half a month (T2), one month (T3), three months (T4), and six months (T5) after onset. Tract-based spatial statistics was used to conduct a voxelwise analysis. RESULTS: The fractional anisotropy (FA) values were significantly lower in the pontine infarction group than in the control group. Then, specific ROIs were analyzed. The FA values of 10 regions of interest were significantly increased at T2 compared with those at T1. The FA value of the corticospinal tract was significantly increased at T3 compared with that at T2. Regional brain activity results showed that the amplitude of low frequency fluctuations value of the frontal lobe decreased at T1, then increased. Finally, The UE-FM scores showed the same increased trend. CONCLUSION: These findings show that the microstructure changes most significantly within half a month after pontine infarction and stabilizes after one month. The recovery of motor function in the later period is mainly caused by changes in the cortex. This facilitates more treatment options.

Signal intensity ratio of draining vein on silent MR angiography as an indicator of high-flow arteriovenous shunt in brain arteriovenous malformation.

OBJECTIVES: To evaluate whether the signal intensity ratio (rSI) of the draining vein on silent MR angiography is correlated with arteriovenous (A-V) transit time on digital subtraction angiography (DSA), thereby identifying high-flow A-V shunt in brain arteriovenous malformation (BAVM), and to analyze whether the rSI and the characteristic of draining veins on silent MRA are associated with hemorrhage presentation. METHODS: Eighty-one draining veins of 46 participants with BAVM (mean age 33.2 ± 16.9 years) who underwent silent MRA and DSA were evaluated retrospectively. The correlation between the rSI of the draining vein on silent MRA and A-V transit time on DSA was examined. The AUC-ROC was obtained to evaluate the performance of the rSI in determining the presence of high-flow A-V shunt. The characteristics of draining veins with the maximum rSI (rSImax) were further compared between the hemorrhagic and non-hemorrhagic untreated BAVM. RESULTS: The rSI of each draining vein on silent MRA was significantly correlated with A-V transit time from DSA (r = -0.81, p < .001). The AUC-ROC was 0.89 for using the rSI to determine the presence of high-flow A-V shunt. A cut-off rSI value of 1.09 yielded a sensitivity of 82.4% and a specificity of 82.8%. The draining vein with rSImax and no ectasia was significantly more observed in the hemorrhagic group (p = 0.045). CONCLUSIONS: The rSI of the draining vein on silent MRA is significantly correlated with A-V transit time on DSA, and it can be used as an indicator of high-flow A-V shunt in BAVM. KEY POINTS: • The signal intensity ratio (rSI) of the draining vein on silent MRA significantly correlated with arteriovenous (A-V) transit time of brain arteriovenous malformation (BAVM) on digital subtraction angiography (DSA). • The area under the receiver operating characteristic curve (AUC) was 0.89 for using the rSI of draining veins to determine high-flow A-V shunt. • Draining veins with maximum rSI and no ectasia were significantly more observed in the hemorrhagic group of BAVM (p = 0.045).

Dynamic contrast-enhanced magnetic resonance imaging biomarkers predict chemotherapeutic responses and survival in primary central-nervous-system lymphoma.

OBJECTIVES: To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the response of chemotherapy and clinical outcomes in primary central-nervous-system lymphoma (PCNSL) patients. METHODS: DCE-MRI in 56 patients enrolled in a prospective study was performed at baseline and 30 days after treatment from 2016 to 2019. Multivariate logistic regression analyses were performed to assess risk factors for tumor responses. The predictive values of related parameters derived from DCE were analyzed via receiver operating characteristic (ROC) curve analysis. To evaluate prognostic factors, the Kaplan-Meier survival analysis with log-rank tests and Cox regression tests were analyzed. RESULTS: Ktrans and Ve were higher in the non-response group than in the response group (p < 0.05). The Ktrans and the percentage of Ktrans decreased after 30 days of treatment were independent predictors of chemotherapy responses (p = 0.034 and p = 0.019). ROC analysis indicated that the cut-off point of Ktrans for predicting chemotherapeutic responses was 0.353 min-1 (AUC, 0.941; 95% CI, 0.87-1; p < 0.001) and percentage of Ktrans decreased after 30 days of treatment was 15.2% (AUC, 0.858; 95% CI, 0.742-0.970; p < 0.001). The greater decrease in Ktrans correlated with a longer progression-free survival (PFS) (χ2 = 13.203, p < 0.001). The higher Ktrans was an independent predictor for shorter PFS (hazard ratio, 10.182; 95% CI, 2.510-41.300; p = 0.001). CONCLUSIONS: Ktrans and Ktrans change measured by DCE-MRI were reliable biomarkers for predicting chemotherapy responses in PCNSL patients. KEY POINTS: • Baseline Ktrans and greater decrease in Ktrans can predict chemotherapeutic efficacy. • DCE-MRI provides quantitative parameters reflecting the tumor microenvironment. • Targeted treatment therapy can be given with more evidence in the future.

Respiratory Variations in Peak Peripheral Artery Velocities and Waveforms for Rapid Assessment of Fluid Responsiveness in Traumatic Shock Patients.

BACKGROUND This study aimed to assess the correlation between the variability of the end-inspiratory and end-expiratory blood flow waveform and fluid responsiveness (FR) in traumatic shock patients who underwent mechanical ventilation by evaluating peripheral arterial blood flow parameters. MATERIAL AND METHODS A cohort of 60 patients with traumatic shock requiring mechanical ventilation-controlled breathing received ultrasound examinations to assess the velocity of carotid artery (CA), femoral artery (FA) and brachial artery (BA). A rehydration test was performed in which of 250 mL of 0.9% saline was administered within 30 min between the first and second measurement of cardiac output by echocardiography. Then, all patients were divided into 2 groups, a responsive group (FR+) and a non-responsive group (FR-). The velocity of end-inspiratory and end-expiratory peripheral arterial blood flow of all patients was ultrasonically measured, and the variability were measured between end-inspiratory and end-expiratory. RESULTS The changes in the end-inspiratory and end-expiratory carotid artery blood flow velocity waveforms of the FR+ groups were significantly different from those of the FR- group (P<0.001). A statistically significant difference in ΔVmax (CA), ΔVmax (BA), and ΔVmax (FA) between these 2 groups was found (all P<0.001). The ROC curve showed that DVmax (CA) and ΔVmax (BA) were more sensitive values to predict FR compared to ΔVmax (FA). The sensitivity of ΔVmax (CA), ΔVmax (FA), and ΔVmax (BA) was 70.0%, 86.7%, and 93.3%, respectively. CONCLUSIONS The study showed that periodic velocity waveform changes in the end-inspiratory and end-expiratory peripheral arterial blood flow can be used for quick assessment of fluid responsiveness.