Integrating Deep Learning-Based Dose Distribution Prediction with Bayesian Networks for Decision Support in Radiotherapy for Upper Gastrointestinal cancer.

Purpose: Selecting the better techniques to harbor optimal motion management, either a stereotactic linear accelerator delivery using TrueBeam (TBX) or Magnetic Resonance (MR)-guided gated delivery using MRIdian (MRG), is time-consuming and costly. To address this challenge, we aimed to develop a decision-supporting algorithm based on a combination of deep learning-generated dose distributions and clinical data. Materials and Methods: We retrospectively analyzed 65 patients with liver or pancreatic cancer who underwent both TBX and MRG simulations and planning process. We trained three-dimensional U-Net deep learning models to predict dose distributions and generated dose volume histograms (DVHs) for each system. We integrated predicted DVH metrics into a Bayesian network (BN) model incorporating clinical data. Results: The MRG prediction model outperformed the TBX model, demonstrating statistically significant superiorities in predicting normalized dose to the PTV and liver. We developed a final BN prediction model integrating the predictive DVH metrics with patient factors like age, PTV size, and tumor location. This BN model an area under the receiver operating characteristic curve index of 83.56%. The decision tree derived from the BN model showed that the tumor location (abutting vs. apart of PTV to hollow viscus organs) was the most important factor to determine TBX or MRG. Conclusion: We demonstrated a decision-supporting algorithm for selecting optimal RT plans in upper gastrointestinal cancers, incorporating both deep learning-based dose prediction and BN-based treatment selection. This approach might streamline the decision-making process, saving resources and improving treatment outcomes for patients undergoing RT.

Ocean weather, biological rates, and unexplained global ecological patterns.

As on land, oceans exhibit high temporal and spatial temperature variation. This "ocean weather" contributes to the physiological and ecological processes that ultimately determine the patterns of species distribution and abundance, yet is often unrecognized, especially in tropical oceans. Here, we tested the paradigm of temperature stability in shallow waters (<12.5 m) across different zones of latitude. We collated hundreds of in situ, high temporal-frequency ocean temperature time series globally to produce an intuitive measure of temperature variability, ranging in scale from quarter-diurnal to annual time spans. To estimate organismal sensitivity of ectotherms (i.e. microbes, algae, and animals whose body temperatures depend upon ocean temperature), we computed the corresponding range of biological rates (such as metabolic rate or photosynthesis) for each time span, assuming an exponential relationship. We found that subtropical regions had the broadest temperature ranges at time spans equal to or shorter than a month, while temperate and tropical systems both exhibited narrow (i.e. stable) short-term temperature range estimates. However, temperature-dependent biological rates in tropical regions displayed greater ranges than in temperate systems. Hence, our results suggest that tropical ectotherms may be relatively more sensitive to short-term thermal variability. We also highlight previously unexplained macroecological patterns that may be underpinned by short-term temperature variability.

Management of Nasal Valve Dysfunction.

Nasal valve dysfunction can substantially impact nasal airflow and overall quality of life. This review provides a comprehensive examination of nasal valve dysfunction, including its mechanisms, classification, and surgical management. The nasal valves include internal and external valves, each of which plays a crucial role in regulating nasal airflow. Subclassification of the external nasal valve into alar and rim valves helps specify the site of obstruction when present and informs the choice of surgical intervention. Dynamic nasal valve obstruction, often characterized by inspiratory collapse of the nasal valve, must be distinguished from static obstruction, which refers to nasal valve stenosis. Accurate identification of the location and mechanism of nasal valve dysfunction is essential for effective management. Various surgical procedures target specific components of the nasal valve and can produce favorable functional outcomes. The selection of surgical procedures, whether individually or in combination, should be tailored to the characteristics of nasal valve dysfunction and the external nasal characteristics of the patient. Strict adherence to proper surgical techniques is imperative for achieving optimal treatment outcomes.

Enhancing Prognostication and Treatment Response Evaluation in Primary CNS Lymphoma with 18F-FDG PET/CT.

BACKGROUND: The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the prognostication and response evaluation of primary central nervous system lymphoma (PCNSL) remains inadequately defined. METHODS: We conducted a retrospective analysis of 268 consecutive newly diagnosed patients with PCNSL between 2006 and 2020. Of these patients, 105 and 110 patients were included to evaluate the prognostic value of baseline and post-treatment 18F-FDG-PET/CT scans, respectively. Tumor uptake was considered positive when it exceeded that of the contralateral brain upon visual assessment. Quantitative analysis of baseline 18F-FDG-PET/CT included measurement of the maximal standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG). RESULTS: The median age of the 268 patients was 62 years (range: 17-85), with 55% being male. The median progression-free survival (PFS) was 24.5 months (95% confidence interval [CI], 19.9-29.1), and the median overall survival (OS) was 34.5 months (95% CI, 22.9-46.1). The average SUVmax was 15.3 ± 5.7 and the mean TMTV and TLG were 12.6 ± 13.9 cm3 and 135.0 ± 152.7 g, respectively. Patients with a baseline TMTV ≥17.0 cm3 had significantly shorter OS (12.5 vs. 74.0 months, p=0.011). Post-treatment metabolic response by 18F-FDG-PET/CT significantly predicted PFS (median: 10.5 vs. 46.0 months, p=0.001) and OS (median: 21.0 vs. 62.0 months, p=0.002), whereas anatomic response by contrast-enhanced MRI showed no statistically significant differences in PFS (p=0.130) or OS (p=0.540). CONCLUSION: Baseline TMTV and post-treatment metabolic response, as assessed by 18F-FDG-PET/CT, are significant prognostic factors in patients with PCNSL.

Conveyor CVD to high-quality and productivity of large-area graphene and its potentiality.

The mass production of high-quality graphene is required for industrial application as a future electronic material. However, the chemical vapor deposition (CVD) systems previously studied for graphene production face bottlenecks in terms of quality, speed, and reproducibility. Herein, we report a novel conveyor CVD system that enables rapid graphene synthesis using liquid precursors. Pristine and nitrogen-doped graphene samples of a size comparable to a smartphone (15 cm × 5 cm) are successfully synthesized at temperatures of 900, 950, and 1000 °C using butane and pyridine, respectively. Raman spectroscopy allows optimization of the rapid-synthesis conditions to achieve uniformity and high quality. By conducting compositional analysis via X-ray photoelectron spectroscopy as well as electrical characterization, it is confirmed that graphene synthesis and nitrogen doping degree can be adjusted by varying the synthesis conditions. Testing the corresponding graphene samples as gas-sensor channels for NH3 and NO2 and evaluating their response characteristics show that the gas sensors exhibit polar characteristics in terms of gas adsorption and desorption depending on the type of gas, with contrasting characteristics depending on the presence or absence of nitrogen doping; nitrogen-doped graphene exhibits superior gas-sensing sensitivity and response speed compared with pristine graphene.

Serum HDL-C subfractions as predictors of cardiovascular calcification in hemodialysis patients: novel insights and clinical implications.

Objective: This study aims to explore the relationship between cardiovascular calcification (CVC) and serum levels of high-density lipoprotein cholesterol (HDL-C) and its subfractions in hemodialysis (HD) patients. Methods: HD patients and healthy participants were recruited based on specific inclusion and exclusion criteria. Various blood indicators were measured, and demographic information was recorded. HDL-C particle levels were quantified using lipophilic fluorescent dye staining and capillary electrophoresis (microfluidic platform). Coronary artery calcium scores and valve calcification were used to classify HD patients into calcification and non-calcification groups. Results: Compared to healthy participants, HD patients showed a significant increase in HDL-C, high-density lipoprotein 2 cholesterol (HDL2-C), and high-density lipoprotein 3 cholesterol (HDL3-C) levels (p < 0.001). Further division of HD patients into calcification and non-calcification groups revealed higher serum HDL3-C concentrations (p = 0.002) and a higher HDL3-C/HDL-C ratio (p = 0.04) in the calcification group. Additionally, elevated HDL3-C levels were found to be an independent risk factor for CVC in HD patients (p = 0.040). The ROC curve analysis showed an AUC value of 0.706 for HDL3-C (p = 0.002). Conclusion: Our study indicates that elevated serum HDL3-C levels in HD patients are an independent risk factor for CVC and can serve as a potential predictor for CVC events. However, more studies need to verify its potential as a predictive indicator..

Ameliorative effects of the mixed aqueous extract of Aurantii Fructus Immaturus and Magnoliae Officinalis Cortex on loperamide-induced STC mice.

Aurantii fructus immaturus (AFI) and Magnoliae Officinalis Cortex (MOC) have been used to treat constipation in China for thousands of years. In this study, a mouse model of slow transit constipation (STC) was established by gavage of loperamide at a dose of 10 mg/kg bw/day for seven days. Seventy-two mice were randomly allocated to six groups (control, STC model, 3 g/kg AFI + MOC, 6 g/kg AFI + MOC, 12 g/kg AFI + MOC, and mosapride). A mixed aqueous extract of AFI and MOC was administered to the STC mice at the corresponding doses from the first day of modelling. Body weight, faecal water content, gastrointestinal transit time, and intestinal propulsion rate were evaluated. Serum levels of neurotransmitters and gastrointestinal hormones, colonic expression of aquaporins (AQP), and interstitial cells of Cajal (ICC) were assessed using ELISA, immunohistochemistry, and Western blot analysis. The abundance and diversity of the gut microbiota were analysed by 16S rRNA gene sequencing. The mixed aqueous extract significantly increased faecal water content and intestinal propulsion rate and shortened gastrointestinal transit time in STC mice. Furthermore, the administration of AFI and MOC significantly decreased serum vasoactive intestinal peptide (VIP), nitric oxide (NO), and somatostatin (SS) levels and increased serum motilin (MTL) levels in STC mice. The protein expression levels of AQP3 and AQP4 in the colon tissue of STC mice significantly decreased following AFI + MOC treatment, whereas those of AQP9 significantly increased. Moreover, the AFI + MOC treatment led to an increase in the number and functionality of ICCs. In addition, the relative abundances of Ruminococcus and Oscillospira increased in response to the administration of AFI + MOC in STC mice. In conclusion, the mixed aqueous extract of AFI and MOC promoted defaecation and increased intestinal mobility in STC mice. Its mechanisms of action involve modulatory effects on neurotransmitters, gastrointestinal hormones, AQPs, and ICCs. AFI + MOC treatment also improved the diversity and abundance of the gut microbiota in STC mice, particularly short-chain fatty acid-producing bacteria, which may play an important role in its beneficial effect on constipation.

The relationship between depression, anxiety and lower urinary tract symptoms in men.

Purpose: Patients with lower urinary tract symptoms (LUTS) often experience comorbid depression and anxiety, yet the mechanisms underlying this association remain incompletely understood. This prospective study aimed to investigate the relationship between depression, anxiety, and LUTS in men. Materials and methods: A prospective study was conducted with 350 male patients who underwent urologic examinations at our institution from January 2021 to December 2021. Of these, 131 patients meeting the inclusion criteria were included. Various questionnaires, including the International Prostate Symptom Score (IPSS) and the Hospital Anxiety and Depression Scale (HADS), as well as LUTS examinations (prostate-specific antigen test, transrectal ultrasonography, and urine flowmetry), were administered. Results: Among the 350 patients, 131 were included in the analysis, with an average age of 58.0 ± 13.69 years. The total IPSS was 18.0 ± 8.69, with the average voiding symptom score at 8.7 ± 5.19 and the average storage symptom score at 6.0 ± 3.27. Both anxiety and depression were found to be correlated with LUTS (P < 0.05). After adjusting for age, hypertension, and diabetes, anxiety (but not depression) was significantly associated with LUTS based on regression analysis. Conclusion: Men with LUTS are more likely to experience anxiety. Therefore, it is essential to assess and address anxiety when managing men with LUTS.

A probiotic NVP1704 alleviates stress-induced sleeplessness/depression-like symptoms in mice by upregulating serotonergic and GABAergic systems and downregulating NF-κB activation.

Sleeplessness (insomnia) is a potential symptom of depression. A probiotic NVP1704 alleviates depression-like behavior and neuroinflammation in mice. Therefore, to understand whether NVP1704 could be effective against sleeplessness in vivo, we exposed immobilization stress (IS) in mice, then orally administered NVP1704 for 5 days, and assayed depression/anxiety-like behavior in the open field, elevated plus maze, and tail suspension tests, sleeping latency time, and sleep duration, euthanized then by exposure to CO2, and analyzed their related biomarkers. Oral administration of NVP1704 decreased IS-induced depression/anxiety-like behavior and sleeping latency time and increased IS-suppressed sleeping duration. NVP1704 increased IS-suppressed expression of γ-aminobutyric acid (GABA), GABAA receptor α1 (GABAARα1) and α2 subunits (GABAARα2), serotonin, 5-HT receptors (5-HT1AR and 5-HT1BR), and melatonin receptors (MT1R and MT2R) in the prefrontal cortex and thalamus. NVP1704 also increased the IS-suppressed GABAARα1-positive cell population in the prefrontal cortex and decreased IS-induced corticosterone, TNF-α, and IL-6 expression and the NF-κB+Iba1+ cell population in the brain and myeloperoxidase, TNF-α, and IL-6 expression and the NF-κB+CD11c+ cell population in the colon. Based on these findings, NVP1704 may alleviate depression/anxiety/sleeplessness-like behaviors through the upregulation of serotonergic and GABAergic systems and downregulation of NF-κB activation.

Biocompatible and nondegradable microcapsules using an ethylamine-bridged EGCG dimer for successful therapeutic cell transplantation.

Conventional alginate microcapsules are widely used for encapsulating therapeutic cells to reduce the host immune response. However, the exchange of monovalent cations with divalent cations for crosslinking can lead to a sol-gel phase transition, resulting in gradual degradation and swelling of the microcapsules in the body. To address this limitation, we present a biocompatible and nondegradable epigallocatechin-3-gallate (EGCG)-based microencapsulation with ethylamine-bridged EGCG dimers (EGCG(d)), denoted as 'Epi-Capsules'. These Epi-Capsules showed increased physical properties and Ca2+ chelating resistance compared to conventional alginate microcapsules. Horseradish peroxidase (HRP) treatment is very effective in increasing the stability of Epi-Capsule((+)HRP) due to the crosslinking between EGCG(d) molecules. Interestingly, the Epi-Capsules(oxi) using a pre-oxidized EGCG(d) can support long-term survival (>90 days) of xenotransplanted insulin-secreting islets in diabetic mice in vivo, which is attributed to its structural stability and reactive oxygen species (ROS) scavenging for lower fibrotic activity. Collectively, this EGCG-based microencapsulation can create Ca2+ chelating-resistance and anti-oxidant activity, which could be a promising strategy for cell therapies for diabetes and other diseases.

Enhancing readmission prediction models by integrating insights from home healthcare notes: Retrospective cohort study.

BACKGROUND: Hospital readmission is an important indicator of inpatient care quality and a significant driver of increasing medical costs. Therefore, it is important to explore the effects of postdischarge information, particularly from home healthcare notes, on enhancing readmission prediction models. Despite the use of Natural Language Processing (NLP) and machine learning in prediction model development, current studies often overlook insights from home healthcare notes. OBJECTIVE: This study aimed to develop prediction models for 30-day readmissions using home healthcare notes and structured data. In addition, it explored the development of 14- and 180-day prediction models using variables in the 30-day model. DESIGN: A retrospective observational cohort study. SETTING(S): This study was conducted at Ajou University School of Medicine in South Korea. PARTICIPANTS: Data from electronic health records, encompassing demographic characteristics of 1819 participants, along with information on conditions, drug, and home healthcare, were utilized. METHODS: Two distinct models were developed for each prediction window (30-, 14-, 180-day): the traditional model, which utilized structured variables alone, and the common data model (CDM)-NLP model, which incorporated structured and topic variables extracted from home healthcare notes. BERTopic facilitated topic generation and risk probability, representing the likelihood of documents being assigned to specific topics. Feature selection involved experimenting with various algorithms. The best-performing algorithm, determined using the area under the receiver operating characteristic curve (AUROC), was used for model development. Model performance was assessed using various learning metrics including AUROC. RESULTS: Among 1819 patients, 251 (13.80 %) experienced 30-day readmission. The least absolute shrinkage and selection operator was used for feature extraction and model development. The 15 structured features were used in the traditional model. Moreover, five additional topic variables from the home healthcare notes were applied in the CDM-NLP model. The AUROC of the traditional model was 0.739 (95 % CI: 0.672-0.807). The AUROC of the CDM-NLP model was high at 0.824 (95 % CI: 0.768-0.880), which indicated an outstanding performance. The topics in the CDM-NLP model included emotional distress, daily living functions, nutrition, postoperative status, and cardiorespiratory issues. In extended prediction model development for 14- and 180-day readmissions, the CDM-NLP consistently outperformed the traditional model. CONCLUSIONS: This study developed effective prediction models using both structured and unstructured data, thereby emphasizing the significance of postdischarge information from home healthcare notes in readmission prediction.

Diagnostic ability of [18F]FDG PET/CT for distinguishing benign from malignant spleen lesions.

OBJECTIVES: [18F]Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is a non-invasive imaging modality used in the differential diagnosis of splenic lesions, although ideal parameters and thresholds remain unclear. The present study evaluated the ability of [18F]FDG PET/CT, including its visual and quantitative parameters, to differentiate between benign and malignant splenic lesions. METHODS: Patients who underwent [18F]FDG PET/CT following the detection of splenic lesions on contrast-enhanced CT were retrospectively analysed. Visual parameters assessed on [18F]FDG PET/CT included whole spleen uptake intensity, lesion multiplicity, and lesion uptake, and quantitative parameters included maximum standardised uptake value (SUVmax), lesion-to-background ratio (LBR), metabolic tumour volume (MTV), total lesion glycolysis (TLG), and lesion size. Parameters differentiating between benign and malignant lesions were evaluated by Pearson's chi-square test, Mann-Whitney U-test, and receiver operating characteristics (ROC) curve analysis. RESULTS: Splenic lesion uptake (p = 0.001) was the only visual parameter significantly distinguishing between benign and malignant lesions. ROC curve analysis demonstrated that SUVmax had the largest area under the ROC, 0.91 (p < 0.001), with an optimal cut-off > 5.3 having a sensitivity of 90.3% and a specificity of 80.6%. Subgroup analysis of malignant lesions showed that SUVmax (p = 0.013), LBR (p = 0.012), and TLG (p = 0.034) were significantly higher in splenic lymphomas than in splenic metastases. CONCLUSION: Of the [18F]FDG PET/CT parameters investigated, SUVmax had the highest accuracy in diagnosing malignant splenic lesions and was significantly higher in splenic lymphomas than in splenic metastases. Visual determination of [18F]FDG uptake by splenic lesions may be an easily evaluated parameter. CLINICAL RELEVANCE STATEMENT: SUVmax and visual grade of [18F]FDG PET/CT help to differentiate spleen lesions. [18F]FDG PET/CT is useful for discriminating between benign and malignant spleen lesions. KEY POINTS: Many splenic lesions are difficult to diagnose on anatomical imaging, with histopathologic analyses are required. SUVmax of PET/CT provided the diagnostic ability to differentiate between benign and malignant splenic lesions. More than normal spleen uptake can be a convenient parameter to diagnose malignant spleen lesions.

Sex-Specific Risk Factors and Clinical Dementia Outcomes for White Matter Hyperintensities in a large South Korean Cohort.

Objective: White matter hyperintensities (WMH) on brain MRI images are the most common feature of cerebral small vessel disease (CSVD). Studies have yielded divergent findings on the modifiable risk factors for WMH and WMH's impact on cognitive decline. Mounting evidence suggests sex differences in WMH burden and subsequent effects on cognition. Thus, we aimed to identify sex-specific modifiable risk factors for WMH. We then explored whether there were sex-specific associations of WMH to longitudinal clinical dementia outcomes. Methods: Participants aged 49-89 years were recruited at memory clinics and underwent a T2-weighted fluid-attenuated inversion recovery (FLAIR) 3T MRI scan to measure WMH volume. Participants were then recruited for two additional follow-up visits, 1-2 years apart, where clinical dementia rating sum of boxes (CDR-SB) scores were measured. We first explored which known modifiable risk factors for WMH were significant when tested for a sex-interaction effect. We additionally tested which risk factors were significant when stratified by sex. We then tested to see whether WMH is longitudinally associated with clinical dementia that is sex-specific. Results: The study utilized data from 713 participants (241 males, 472 females) with a mean age of 72.3 years and 72.8 years for males and females, respectively. 57.3% and 59.5% of participants were diagnosed with mild cognitive impairment (MCI) for males and females, respectively. 40.7% and 39.4% were diagnosed with dementia for males and females, respectively. Of the 713 participants, 181 participants had CDR-SB scores available for three longitudinal time points. Compared to males, females showed stronger association of age to WMH volume. Type 2 Diabetes was associated with greater WMH burden in females but not males. Finally, baseline WMH burden was associated with worse clinical dementia outcomes longitudinally in females but not in males. Discussion: Elderly females have an accelerated increase in cerebrovascular burden as they age, and subsequently are more vulnerable to clinical dementia decline due to CSVD. Additionally, females are more susceptible to the cerebrovascular consequences of diabetes. These findings emphasize the importance of considering sex when examining the consequences of CSVD. Future research should explore the underlying mechanisms driving these sex differences and personalized prevention and treatment strategies. Clinical trial registration: The BICWALZS is registered in the Korean National Clinical Trial Registry (Clinical Research Information Service; identifier, KCT0003391). Registration Date 2018/12/14.

Neuroimaging and natural language processing-based classification of suicidal thoughts in major depressive disorder.

Suicide is a growing public health problem around the world. The most important risk factor for suicide is underlying psychiatric illness, especially depression. Detailed classification of suicide in patients with depression can greatly enhance personalized suicide control efforts. This study used unstructured psychiatric charts and brain magnetic resonance imaging (MRI) records from a psychiatric outpatient clinic to develop a machine learning-based suicidal thought classification model. The study included 152 patients with new depressive episodes for development and 58 patients from a geographically different hospital for validation. We developed an eXtreme Gradient Boosting (XGBoost)-based classification models according to the combined types of data: independent components-map weightings from brain T1-weighted MRI and topic probabilities from clinical notes. Specifically, we used 5 psychiatric symptom topics and 5 brain networks for models. Anxiety and somatic symptoms topics were significantly more common in the suicidal group, and there were group differences in the default mode and cortical midline networks. The clinical symptoms plus structural brain patterns model had the highest area under the receiver operating characteristic curve (0.794) versus the clinical notes only and brain MRI only models (0.748 and 0.738, respectively). The results were consistent across performance metrics and external validation. Our findings suggest that focusing on personalized neuroimaging and natural language processing variables improves evaluation of suicidal thoughts.

Breast Augmentation Preferences and Concerns Among Chinese Women: A Nationwide Multicenter Study of 2066 Cases.

BACKGROUND: Research studies on Asian women's preferences for breast augmentation and the factors that influence decision-making are scarce or unrepresentative. METHODS: This study was conducted from September 2016 to September 2017, a period of one year. We developed a questionnaire for Chinese female with breast augmentation intentions based on the Breast-Q questionnaire, the world's most popular breast augmentation assessment tool, and conducted questionnaire surveys in 35 hospitals located in 19 provinces in mainland China among female who came to hospitals to inquire about breast augmentation surgery. RESULTS: A total of 2066 questionnaires were collected from female interested in breast augmentation. The age range at the time of response was 19-53 years (mean 31.2 ± 6.8 years). More than half of the respondents (58.1%) were married, and 70.4% of them had children. The respondents rated their dressed image significantly higher than their nude image. Their partners also rated their breast image poorly, with 43% rating it fair and 30.4% negatively. Internal reasons, such as improving self-confidence and creating a better body image, were the main motivators for breast augmentation. More than half of the respondents had only limited understanding of breast augmentation surgery or had heard of it but did not fully understand it (33.2% and 27.5%, respectively), and 69.4% had considered breast augmentation for less than three years. A total of 49.2% of the respondents learned about breast augmentation surgery through the Internet. A total of 43.8% of the respondents did not receive support from family members or partners. Surgical safety (20.4%), surgical effect (17.1%), and surgeon's skill (16.6%) were given the highest priority. The surgeon's professionalism, popularity, and academic background were also high on people's list of considerations. CONCLUSIONS: The results of our breast augmentation survey provide data on many Chinese women considering breast augmentation. This will help plastic surgeons better understand the characteristics, preferences, and concerns of Chinese women undergoing breast augmentation and will be used to guide patient-doctor communication and help Chinese women make the most informed decisions. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Hsp47 promotes biogenesis of multi-subunit neuroreceptors in the endoplasmic reticulum.

Protein homeostasis (proteostasis) deficiency is an important contributing factor to neurological and metabolic diseases. However, how the proteostasis network orchestrates the folding and assembly of multi-subunit membrane proteins is poorly understood. Previous proteomics studies identified Hsp47 (Gene: SERPINH1), a heat shock protein in the endoplasmic reticulum lumen, as the most enriched interacting chaperone for gamma-aminobutyric acid type A (GABAA) receptors. Here, we show that Hsp47 enhances the functional surface expression of GABAA receptors in rat neurons and human HEK293T cells. Furthermore, molecular mechanism study demonstrates that Hsp47 acts after BiP (Gene: HSPA5) and preferentially binds the folded conformation of GABAA receptors without inducing the unfolded protein response in HEK293T cells. Therefore, Hsp47 promotes the subunit-subunit interaction, the receptor assembly process, and the anterograde trafficking of GABAA receptors. Overexpressing Hsp47 is sufficient to correct the surface expression and function of epilepsy-associated GABAA receptor variants in HEK293T cells. Hsp47 also promotes the surface trafficking of other Cys-loop receptors, including nicotinic acetylcholine receptors and serotonin type 3 receptors in HEK293T cells. Therefore, in addition to its known function as a collagen chaperone, this work establishes that Hsp47 plays a critical and general role in the maturation of multi-subunit Cys-loop neuroreceptors.

Scutellarin inhibits inflammatory PANoptosis by diminishing mitochondrial ROS generation and blocking PANoptosome formation.

PANoptosis is manifested with simultaneous activation of biomarkers for both pyroptotic, apoptotic and necroptotic signaling via the molecular platform PANoptosome and it is involved in pathologies of various inflammatory diseases including hemophagocytic lymphohistiocytosis (HLH). Scutellarin is a flavonoid isolated from herbal Erigeron breviscapus (Vant.) Hand.-Mazz. and has been shown to possess multiple pharmacological effects, but it is unknown whether scutellarin has any effects on PANoptosis and related inflammatory diseases. In this study, we found that scutellarin inhibited cell death in bone marrow-derived macrophages (BMDMs) and J774A.1 cells treated with TGF-ß-activated kinase 1 (TAK1) inhibitor 5Z-7-oxozeaenol (OXO) plus lipopolysaccharide (LPS), which has been commonly used to induce PANoptosis. Western blotting showed that scutellarin dose-dependently inhibited the activation biomarkers for pyroptotic (Caspase-1p10 and GSDMD-NT), apoptotic (cleaved Casp3/8/9 and GSDME-NT), and necroptotic (phosphorylated MLKL) signaling. The inhibitory effect of scutellarin was unaffected by NLRP3 or Caspase-1 deletion. Interestingly, scutellarin blocked the assembly of PANoptosome that encompasses ASC, RIPK3, Caspase-8 and ZBP1, suggesting its action on upstream signaling. Consistent with this, scutellarin inhibited mitochondrial damage and mitochondrial reactive oxygen species (mtROS) generation in cells treated with OXO+LPS. Further, mito-TEMPO that can scavenge mtROS significantly inhibited OXO+LPS-induced PANoptotic cell death. In line with the in vitro results, scutellarin markedly alleviated systemic inflammation, multiple organ injury, and activation of PANoptotic biomarkers in mice with HLH. Collectively, our data suggest that scutellarin can inhibit PANoptosis by suppressing mitochondrial damage and mtROS generation and thereby mitigating multiple organ injury in mice with inflammatory disorders.

Comparison of digital and analog [68Ga]Ga-PSMA-11 PET/CT for detecting post-prostatectomy biochemical recurrence in prostate cancer patients: a prospective study.

Digital positron emission tomography/computed tomography (PET/CT) has shown enhanced sensitivity and spatial resolution compared with analog PET/CT. The present study compared the diagnostic performance of digital and analog PET/CT with [68Ga]Ga-PSMA-11 in prostate cancer patients who experienced biochemical recurrence (BCR) after prostatectomy. Forty prostate cancer patients who experienced BCR, defined as serum prostate-specific antigen (PSA) concentrations exceeding 0.2 ng/mL after prostatectomy, were prospectively recruited. These patients were stratified into three groups based on their serum PSA levels. [68Ga]Ga-PSMA-11 was injected into each patient, and images were acquired using both analog and digital PET/CT scanners. Analog and digital PET/CT showed comparable lesion detection rate (71.8% vs. 74.4%), sensitivity (85.0% vs. 90.0%), and positive predictive value (PPV, 100.0% vs. 100.0%). However, digital PET/CT detected more lesions (139 vs. 111) and had higher maximum standardized uptake values (SUVmax, 14.3 vs. 10.3) and higher kappa index (0.657 vs. 0.502) than analog PET/CT, regardless of serum PSA levels. On both analog and digital PET/CT, lesion detection rates and interrater agreement increased with increasing serum PSA levels. Compared with analog PET/CT, digital PET/CT detected more lesions with a higher SUVmax and better interrater agreement in prostate cancer patients who experienced BCR after prostatectomy.

Flight or fight: different strategies of intertidal periwinkle Littoraria sinensis coping with high temperature across populations.

Intertidal organisms usually live near their upper thermal limits, and are vulnerable to future global warming. As a vital response to thermal stress, thermoregulatory strategy in physiological and behavioral performance is essential for organisms coping with thermal stress and surviving the changing world. To investigate the relationship between the thermoregulatory strategy and habitat temperature, in the present study, we comparatively investigated the thermal responsive strategy among different geographic populations of the supralittoral snail Littoraria sinensis by determining snails' cardiac function and behavioral performance. Our results indicated that populations inhabiting high ambient temperatures had higher sublethal temperatures (i.e. Arrhenius breakpoint temperatures, ABTs, the temperature at which the heart rate shapely decreases with further heating) and lethal temperatures (i.e. Flatline temperatures, FLTs, the temperature at which heart rate ceases), and behaved less actively (e.g. shorter moving distances and shorter moving time) in the face of high and rising temperatures-a physiological fight strategy. On the other hand, populations at relatively low ambient temperatures had relatively lower physiological upper thermal limits with lower ABTs and FLTs and moved more actively in the face of high and rising temperatures-a behavioral flight strategy. These results demonstrate that the thermoregulatory strategies of the snails are closely related to their habitat temperatures and are different among populations surviving divergent thermal environments.

Facile Fabrication of Multifunctional Hydrogel Nanoweb Coating Using Carboxymethyl Chitosan-Based Short Nanofibers for Blood-Contacting Medical Devices.

Blood-contacting medical devices (BCDs) require antithrombotic, antibacterial, and low-friction surfaces. Incorporating a nanostructured surface with the functional hydrogel onto BCD surfaces can enhance the performances; however, their fabrication remains challenging. Here, we introduce a straightforward method to fabricate a multifunctional hydrogel-based nanostructure on BCD surfaces using O-carboxymethyl chitosan-based short nanofibers (CMC-SNFs). CMC-SNFs, fabricated via electrospinning and cutting processes, are easily sprayed and entangled onto the BCD surface. The deposited CMC-SNFs form a robust nanoweb layer via fusion at the contact area of the nanofiber interfaces. The superhydrophilic CMC-SNF nanoweb surface creates a water-bound layer that effectively prevents the nonspecific adhesion of bacteria and blood cells, thereby enhancing both antimicrobial and antithrombotic performances. Furthermore, the CMC-SNF nanoweb exhibits excellent lubricity and durability on the bovine aorta. The demonstration results of the CMC-SNF coating on catheters and sheaths provide evidence of its capability to apply multifunctional surfaces simply for diverse BCDs.