Search

Autism spectrum disorder (ASD) is characterized by social interaction deficits and repetitive behaviors. Recent research has linked that gut dysbiosis may contribute to ASD-like behaviors. However, the exact developmental time point at which gut microbiota alterations affect brain function and behavior in patients with ASD remains unclear. We hypothesized that ASD-related brain microstructural changes and gut dysbiosis induce metabolic dysregulation and proinflammatory responses, which collectively contribute to the social behavioral deficits observed in early childhood. We used an autistic-like rat model that was generated via prenatal valproic acid exposure. We analyzed brain microstructural changes using diffusion tensor imaging (DTI) and examined microbiota, blood, and fecal samples for inflammation biomarkers. The ASD model rats exhibited significant brain microstructural changes in the anterior cingulate cortex, hippocampus, striatum, and thalamus; reduced microbiota diversity (Prevotellaceae and Peptostreptococcaceae); and altered metabolic signatures. The shift in microbiota diversity and density observed at postnatal day (PND) 35, which is a critical developmental period, underscored the importance of early ASD interventions. We identified a unique metabolic signature in the ASD model, with elevated formate and reduced acetate and butyrate levels, indicating a dysregulation in short-chain fatty acid (SCFA) metabolism. Furthermore, increased astrocytic and microglial activation and elevated proinflammatory cytokines-interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α)-were observed, indicating immune dysregulation. This study provided insights into the complex interplay between the brain and the gut, and indicated DTI metrics as potential imaging-based biomarkers in ASD, thus emphasizing the need for early childhood interventions., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Approximately 50% of melanoma patients fail to respond to immune checkpoint blockade (ICB), and acquired resistance hampers long-term survival in about half of initially responding patients. Whether targeting BET reader proteins, implicated in epigenetic dysregulation, can enhance ICB response rates and durability, remains to be determined. Here we show elevated BET proteins correlate with poor survival and ICB responses in melanoma patients. The BET inhibitor IBET151, combined with anti-CTLA-4, overcame innate ICB resistance however, sequential BET inhibition failed against acquired resistance in mouse models. Combination treatment response in the innate resistance model induced changes in tumor-infiltrating immune cells, reducing myeloid-derived suppressor cells (MDSCs). CD4+ and CD8+ T cells showed decreased expression of inhibitory receptors, with reduced TIM3, LAG3, and BTLA checkpoint expression. In human PBMCs in vitro, BET inhibition reduced expression of immune checkpoints in CD4+ and CD8+ T cells, restoring effector cytokines and downregulating the transcriptional driver TOX. BET proteins in melanoma may play an oncogenic role by inducing immune suppression and driving T cell dysfunction. The study demonstrates an effective combination for innately unresponsive melanoma patients to checkpoint inhibitor immunotherapy, yet highlights BET inhibitors' limitations in an acquired resistance context., (© 2024 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)

Objective: When performing radiofrequency ablation for thyroid nodules, it is essential to avoid thermal injury to the recurrent laryngeal nerve. This porcine animal model study used continuous intraoperative neuromonitoring to investigate the thermal safety parameters of thyroid radiofrequency ablation., Study Design: Porcine animal study., Setting: University animal laboratory., Methods: Twelve piglets were tested at different radiofrequency power levels, and the real-time electromyography signal changes were recorded under continuous intraoperative neuromonitoring. The spread heat study (8 piglets) included spontaneous recovery tests and cold water irrigation tests to investigate the safety distance from the recurrent laryngeal nerve to the active tip during 5-second activation with standard stimulation patterns. The residual heat study (4 piglets) investigated the safety cooling durations by touching the recurrent laryngeal nerve with the tip after a 5-second activation., Results: In the spread heat study, substantial signal attenuation events were observed at an spread heat distance of 2, 3, 5, and 5 mm when the power was set as 10, 20, 30, and 50 W, respectively. No signal recovery could be observed in 20 minutes with or without cold water irrigation in the injured recurrent laryngeal nerve area. The residual heat study shows the residual thermal effect of the tip is minimal, and no substantial signal attenuation event was observed at all experiments., Conclusions: This innovative study established the thermal safety parameters for radiofrequency ablation in a porcine model at various power levels, which can potentially assist operators in delineating a precise ablation field and providing effective thyroid ablation treatment safely., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objectives: To investigate whether using the BioFire® FilmArray® Blood Culture Identification 2 panel (BCID2) leads to timely antimicrobial therapy and improves patient outcomes in critically ill patients with bloodstream infections (BSIs)., Methods: This retrospective observational study included patients with BSIs admitted to the intensive care unit from July 1, 2021, to August 31, 2023. Patients were divided into groups receiving appropriate or inappropriate antimicrobial therapy. Those receiving inappropriate therapy underwent adjustments using standard-of-care (SOC) testing or BCID2. Propensity score matching (PSM) was performed on the original cohort (Model 1) and a time-window bias-adjusted cohort (Model 2). Clinical impact of BCID2-guided antimicrobial adjustment was analysed in both models., Results: A total of 181 patients received inappropriate antimicrobial therapy, with 33 undergoing BCID2 testing and 148 undergoing SOC testing. Following PSM and time-window bias adjustment, 66 patients were analysed in Model 1 and 46 patients in Model 2. BCID2 significantly reduced the median time to appropriate antimicrobial therapy (40.8 vs. 74.0 h in Model 1; 42.8 vs. 68.9 h in Model 2) and the day-28 mortality rate (27.8% vs. 77.1%, P < 0.001 in Model 1; 23.5% vs. 58.6%, P = 0.021 in Model 2). In multivariate regression analysis, BCID2-guided antimicrobial adjustment was an independent prognostic factor for day-28 mortality (adjusted odds ratio [aOR] 0.07 in Model 1 and aOR 0.12 in Model 2)., Conclusion: BCID2-guided antimicrobial stewardship was associated with a shorter time to appropriate antimicrobial therapy and reduced day-28 mortality in critically ill patients with BSIs receiving inappropriate antimicrobial therapy., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

The outbreak of the coronavirus disease 2019 (COVID-19) pandemic threatened adolescents' mental health and livelihoods, which can worsen their non-suicidal self-injury (NSSI) behaviors. With the significant increase of total online time use, adolescents become more prone to problematic internet use (PIU). This study examined whether depression mediated the relationship between PIU and NSSI among adolescence during the COVID-19 outbreak. Constructed with a cross-sectional design during the COVID-19 outbreak in Taiwan, 1060 participants were drawn from junior high schools through stratified and cluster sampling, and completed a set of comprehensive surveys. The mediation model demonstrated a good fit to the data, GFI = .96, CFI = .97, NFI = .97, NNFI = .95, IFI = .97, and SRMR = .02. The overall fit of the mediational model was adequate. The path from PIU to depression, β = .41, p < .001, and the path from depression to NSSI, β = .40, p < .001, were both significant. Moreover, the effect of PIU to NSSI decreased from .23 (p < .001) to .05 (p = .099) when depression was incorporated into the analysis. Moreover, results in bootstrapping analysis displayed that the indirect effect (PIU on NSSI via depression) was statistically significant (p < .001) and the direct effect (PIU on NSSI) was statistically non-significant (p = .134). The full mediation model was confirmed. The findings of the structure equation modeling and bootstrap analysis showed that PIU significantly and positively predicted NSSI, and that depression fully mediated this relationship., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background/objective: The genetic landscape of sensorineural hearing impairment (SNHI) varies across populations. In Mongolia, previous studies have shown a lower prevalence of GJB2 mutations and a higher frequency of variants in other deafness-related genes. This study aimed to investigate the genetic variants associated with idiopathic SNHI in Mongolian patients., Methods: We utilized the next-generation sequencing for investigating the causative mutations in 99 Mongolian patients with SNHI., Results: We identified pathogenic variants in 53 of the 99 SNHI patients (54%), with SLC26A4 being the most frequently mutated gene. The c.919-2A>G variant in SLC26A4 was the most prevalent, accounting for 46.2% of the mutant alleles. In addition, we identified 19 other known and 21 novel mutations in a total of 21 SNHI genes in autosomal recessive or dominant inheritance patterns., Conclusions: Our findings expand the understanding of the genetic landscape of SNHI in Mongolia and highlight the importance of considering population-specific variations in genetic testing and counseling for SNHI.

Objective. With prolonged life expectancy, the incidence of memory deficits, especially in Alzheimer's disease (AD), has increased. Although multiple treatments have been evaluated, no promising treatment has been found to date. Deep brain stimulation (DBS) of the fornix area was explored as a possible treatment because the fornix is intimately connected to memory-related areas that are vulnerable in AD; however, a proper imaging biomarker for assessing the therapeutic efficiency of forniceal DBS in AD has not been established. Approach. This study assessed the efficacy and safety of DBS by estimating the optimal intersection volume between the volume of tissue activated and the fornix. Utilizing a gold-electroplating process, the microelectrode's surface area on the neural probe was increased, enhancing charge transfer performance within potential water window limits. Bilateral fornix implantation was conducted in triple-transgenic AD mice (3 × Tg-AD) and wild-type mice (strain: B6129SF1/J), with forniceal DBS administered exclusively to 3 × Tg-AD mice in the DBS-on group. Behavioral tasks, diffusion tensor imaging (DTI), and immunohistochemistry (IHC) were performed in all mice to assess the therapeutic efficacy of forniceal DBS. Main results. The results illustrated that memory deficits and increased anxiety-like behavior in 3 × Tg-AD mice were rescued by forniceal DBS. Furthermore, forniceal DBS positively altered DTI indices, such as increasing fractional anisotropy (FA) and decreasing mean diffusivity (MD), together with reducing microglial cell and astrocyte counts, suggesting a potential causal relationship between revised FA/MD and reduced cell counts in the anterior cingulate cortex, hippocampus, fornix, amygdala, and entorhinal cortex of 3 × Tg-AD mice following forniceal DBS. Significance. The efficacy of forniceal DBS in AD can be indicated by alterations in DTI-based biomarkers reflecting the decreased activation of glial cells, suggesting reduced neural inflammation as evidenced by improvements in memory and anxiety-like behavior., (Creative Commons Attribution license.)

Background and Objectives: This study examined the psychometric properties and measurement invariance of the 10-item Awareness of Age-Related Change Short Form (AARC-SF) questionnaire in a Chinese-speaking sample of older adults in Taiwan., Research Design and Methods: Data from 292 participants (Mage = 77.64 years) in the Healthy Aging Longitudinal Study in Taiwan cohort were used for Study 1, whereas data from young-old adult samples in Germany were used for Study 2., Results: Study 1 showed that the AARC-SF had satisfactory reliability and validity for assessing adults' AARC in Taiwan. Analyses confirmed the 2-factor structure of AARC-gains and AARC-losses. Study 2 demonstrated strong measurement invariance across men and women, whereas direct comparisons of the item scores between young-old adults and old-old adults need to be made with caution. Noninvariance of loadings indicated that certain items were more closely linked to AARC-gains and AARC-losses in Taiwan than in Germany. Noninvariance of intercepts suggested potential biases in comparing item scores between Taiwanese and German older adults., Discussion and Implications: The AARC-SF emerged as a reliable and valid instrument for capturing positive and negative subjective aging experiences among Taiwanese older adults. However, it is noteworthy that some items on the AARC-SF may solicit different responses from individuals of different ages and different countries of origin, requiring caution with age group and cross-cultural comparisons., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Objectives: During the early COVID-19 pandemic, college students had to switch to an online learning and online communication environment facing the chances of information overload, misinformation or conflicting information about COVID-19. This study aims to assess the communication needs that have arisen among college students to shed light on the development of a health communication campaign tailored toward college students. Methods: A series of 10 focus group discussions were conducted with 38 total participants. Each group has 2-6 undergraduate or graduate student participants. Nvivo was used to analyze the transcripts. Results: The students reported that they received conflicting information or misinformation. They requested messages with language that was easy to understand with infographics while being culturally appropriate. They advocated for regular and concise email updates from campus leadership. Most participants also preferred COVID-19 control and prevention information on social media. Conclusion: This study revealed the current status and the needs for health information about COVID-19 prevention and control among college students.

Marked differences in survival from melanoma are noted between men and women that cannot be accounted for by behavioral differences. We and others have provided evidence that this difference may be due to increased expression of immune-related genes from the second X chromosome because of failure of X inactivation. In the present review, we have examined evidence for the contrary view that survival differences are due to weaker immune responses in males. One reason for this may be the loss of Y chromosomes (LOY), particularly in older males. The genes involved may have direct roles in immune responses or be noncoding RNAs that regulate both sex and autosomal genes involved in immune responses or tumor growth. Loss of the KDM6C and KDM5D demethylases appeared to common genes involved. The second factor appears to be the activation of androgen receptors (AR) on melanoma cells that increase their invasiveness and growth. Induction of T-cell exhaustion by AR that limits immune responses against melanoma appeared a common finding. The development of treatments to overcome effects related to gene loss on Y poses challenges, but several avenues related to AR signaling appear worthy of further study in the treatment of metastatic disease., (© 2024 The Author(s). Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)

Background: The increasing prevalence of drug-resistant pathogens leads to delays in adequate antimicrobial treatment in intensive care units (ICU). The real-world influence of the BioFire FilmArray Blood Culture Identification 2 (BCID2) panel on pathogen identification, diagnostic concordance with conventional culture methods, and antimicrobial stewardship in the ICU remains unexplored., Methods: This retrospective observational study, conducted from July 2021 to August 2023, involved adult ICU patients with positive blood cultures who underwent BCID2 testing. The concordance between BCID2 and conventional culture results was examined, and its impact on antimicrobial stewardship was assessed through a comprehensive retrospective review of patient records by intensivists., Results: A total of 129 blood specimens from 113 patients were analysed. Among these patients, a high proportion of drug-resistant strains were noted, including carbapenem-resistant Klebsiella pneumoniae (CRKP) (57.1%), carbapenem-resistant Acinetobacter calcoaceticus-baumannii complex (100%), methicillin-resistant Staphylococcus aureus (MRSA) (70%), and vancomycin-resistant Enterococcus faecium (VRE) (100%). The time from blood culture collection to obtaining BCID2 results was significantly shorter than conventional culture (46.2 h vs. 86.9 h, p < 0.001). BCID2 demonstrated 100% concordance in genotype-phenotype correlation in antimicrobial resistance (AMR) for CRKP, carbapenem-resistant Escherichia coli, MRSA, and VRE. A total of 40.5% of patients received inadequate empirical antimicrobial treatment. The antimicrobial regimen was adjusted or confirmed in 55.4% of patients following the BCID2 results., Conclusions: In the context of a high burden of drug-resistant pathogens, BCID2 demonstrated rapid pathogen and AMR detection, with a noticeable impact on antimicrobial stewardship in BSI in the ICU., (Copyright © 2024. Published by Elsevier B.V.)

Prcis: Machine learning classifiers are an effective approach to detecting glaucomatous fundus images based on optic disc topographic features making it a straightforward and effective approach., Study Design: Retrospective case-control study., Objective: The aim was to compare the effectiveness of clinical discriminant rules and machine learning classifiers in identifying glaucomatous fundus images based on optic disc topographic features., Methods: The study used a total of 800 fundus images, half of which were glaucomatous cases and the other half non-glaucomatous cases obtained from an open database and clinical work. The images were randomly divided into training and testing sets with equal numbers of glaucomatous and non-glaucomatous images. An ophthalmologist framed the edge of the optic cup and disc, and the program calculated five features, including the vertical cup-to-disc ratio and the width of the optic rim in four quadrants in pixels, used to create machine learning classifiers. The discriminative ability of these classifiers was compared with clinical discriminant rules., Results: The machine learning classifiers outperformed clinical discriminant rules, with the extreme gradient boosting method showing the best performance in identifying glaucomatous fundus images. Decision tree analysis revealed that the cup-to-disc ratio was the most important feature for identifying glaucoma fundus images. At the same time, the temporal width of the optic rim was the least important feature., Conclusions: Machine learning classifiers are an effective approach to detecting glaucomatous fundus images based on optic disc topographic features and integration with an automated program for framing and calculating the required parameters would make it a straightforward and effective approach., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The rapid advancements in Artificial Intelligence of Things (AIoT) are pivotal for the healthcare sector, especially as the world approaches an aging society which will be reached by 2050. This paper presents an innovative AIoT-enabled data fusion system implemented at the CMUH Respiratory Intensive Care Unit (RICU) to address the high incidence of medical errors in ICUs, which are among the top three causes of mortality in healthcare facilities. ICU patients are particularly vulnerable to medical errors due to the complexity of their conditions and the critical nature of their care. We introduce a four-layer AIoT architecture designed to manage and deliver both real-time and non-real-time medical data within the CMUH-RICU. Our system demonstrates the capability to handle 22 TB of medical data annually with an average delay of 1.72 ms and a bandwidth of 65.66 Mbps. Additionally, we ensure the uninterrupted operation of the CMUH-RICU with a three-node streaming cluster (called Kafka), provided a failed node is repaired within 9 h, assuming a one-year node lifespan. A case study is presented where the AI application of acute respiratory distress syndrome (ARDS), leveraging our AIoT data fusion approach, significantly improved the medical diagnosis rate from 52.2% to 93.3% and reduced mortality from 56.5% to 39.5%. The results underscore the potential of AIoT in enhancing patient outcomes and operational efficiency in the ICU setting., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: The optimal timing for applying the BioFire FilmArray Pneumonia Panel (FAPP) in intensive care unit (ICU) patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) remains undefined, and there are limited data on its impact on antimicrobial stewardship., Methods: This retrospective study was conducted at a referral hospital in Taiwan from November 2019 to October 2022. Adult ICU patients with HAP/VAP who underwent FAPP testing were enrolled. Patient data, FAPP results, conventional microbiological testing results, and the real-world impact of FAPP results on antimicrobial therapy adjustments were assessed. Logistic regression was used to determine the predictive factors for bacterial detection by FAPP., Results: Among 592 respiratory specimens, including 564 (95.3%) endotracheal aspirate specimens, 19 (3.2%) expectorated sputum specimens and 9 (1.5%) bronchoalveolar lavage specimens, from 467 patients with HAP/VAP, FAPP testing yielded 368 (62.2%) positive results. Independent predictors for positive bacterial detection by FAPP included prolonged hospital stay (odds ratio [OR], 3.14), recent admissions (OR, 1.59), elevated C-reactive protein levels (OR, 1.85), Acute Physiology and Chronic Health Evaluation II scores (OR, 1.58), and septic shock (OR, 1.79). Approximately 50% of antimicrobial therapy for infections caused by Gram-negative bacteria and 58.4% for Gram-positive bacteria were adjusted or confirmed after obtaining FAPP results., Conclusions: This study identified several factors predicting bacterial detection by FAPP in critically ill patients with HAP/VAP. More than 50% real-world clinical practices were adjusted or confirmed based on the FAPP results. Clinical algorithms for the use of FAPP and antimicrobial stewardship guidelines may further enhance its benefits., Competing Interests: Declaration of competing interest No conflicts exist for the specified authors., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: This study aimed to investigate the distinct yet interconnected aspects of social isolation, namely living alone and loneliness, and their individual and combined effects on predicting health-related quality of life (HRQoL)., Methods: A comprehensive analysis, encompassing both cross-sectional and longitudinal approaches, was conducted using a nationally representative sample of 5644 community-dwelling adults aged 55 and older from the Healthy Aging Longitudinal Study in Taiwan (HALST)., Results: Baseline data revealed that 9% of the sample reported living alone, while 10.3% reported experiencing loneliness, with 2.5% reporting both living alone and feeling lonely. Regression analyses consistently demonstrated that loneliness was significantly associated with concurrent and subsequent lower physical (PCS) and mental (MCS) component of HRQoL. Conversely, additional analyses indicated that living alone could indirectly exacerbate the adverse effects of loneliness or contribute to prolonged feelings of loneliness, subsequently predicting lower HRQoL after 3.2 year., Conclusion: In terms of practical implications, interventions and policies aiming to enhance HRQoL in older adults should give particular attention to those who report feelings of loneliness, especially individuals living alone., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The clinical success of dental titanium implants is profoundly linked to implant stability and osseointegration, which comprises pre-osteoblast proliferation, osteogenic differentiation, and extracellular mineralization. Because of the bio-inert nature of titanium, surface processing using subtractive or additive methods enhances osseointegration ability but limits the benefit due to accompanying surface contamination. By contrast, laser processing methods increase the roughness of the implant surface without contamination. However, the effects of laser-mediated distinct surface structures on the osteointegration level of osteoblasts are controversial. The role of a titanium surface with a laser-mediated microchannel structure in pre-osteoblast maturation remains unclear. This study aimed to elucidate the effect of laser-produced microchannels on pre-osteoblast maturation. Pre-osteoblast human embryonic palatal mesenchymal cells were seeded on a titanium plate treated with grinding (G), sandblasting with large grit and acid etching (SLA), or laser irradiation (L) for 3-18 days. The proliferation and morphology of pre-osteoblasts were evaluated using a Trypan Blue dye exclusion test and fluorescence microscopy. The mRNA expression, protein expression, and protein secretion of osteogenic differentiation markers in pre-osteoblasts were evaluated using reverse transcriptase quantitative polymerase chain reaction, a Western blot assay, and a multiplex assay, respectively. The extracellular calcium precipitation of pre-osteoblast was measured using Alizarin red S staining. Compared to G- and SLA-treated titanium surfaces, the laser-produced microchannel surfaces enhanced pre-osteoblast proliferation, the expression/secretion of osteogenic differentiation markers, and extracellular calcium precipitation. Laser-treated titanium implants may enhance the pre-osteoblast maturation process and provide extra benefits in clinical application.

Rationale: Multiple copies in T-cell malignancy 1 (MCT-1) is a prognostic biomarker for aggressive breast cancers. Overexpressed MCT-1 stimulates the IL-6/IL-6R/gp130/STAT3 axis, which promotes epithelial-to-mesenchymal transition and cancer stemness. Because cancer stemness largely contributes to the tumor metastasis and recurrence, we aimed to identify whether the blockade of MCT-1 and IL-6R can render these effects and to understand the underlying mechanisms that govern the process. Methods: We assessed primary tumor invasion, postsurgical local recurrence and distant metastasis in orthotopic syngeneic mice given the indicated immunotherapy and MCT-1 silencing (shMCT-1). Results: We found that shMCT-1 suppresses the transcriptomes of the inflammatory response and metastatic signaling in TNBC cells and inhibits tumor recurrence, metastasis and mortality in xenograft mice. IL-6R immunotherapy and shMCT-1 combined further decreased intratumoral M2 macrophages and T regulatory cells (Tregs) and avoided postsurgical TNBC expansion. shMCT-1 also enhances IL-6R-based immunotherapy effectively in preventing postsurgical TNBC metastasis, recurrence and mortality. Anti-IL-6R improved helper T, cytotoxic T and natural killer (NK) cells in the lymphatic system and decreased Tregs in the recurrent and metastatic tumors. Combined IL-6R and PD-L1 immunotherapies abridged TNBC cell stemness and M2 macrophage activity to a greater extent than monotherapy. Sequential immunotherapy of PD-L1 and IL-6R demonstrated the best survival outcome and lowest postoperative recurrence and metastasis compared with synchronized therapy, particularly in the shMCT-1 context. Multiple positive feedforward loops of the MCT-1/IL-6/IL-6R/CXCL7/PD-L1 axis were identified in TNBC cells, which boosted metastatic niches and immunosuppressive microenvironments. Clinically, MCT-1 high /PD-L1 high /CXCL7 high and CXCL7 high /IL-6 high /IL-6R high expression patterns predict worse prognosis and poorer survival of breast cancer patients. Conclusion: Systemic targeting the MCT-1/IL-6/IL-6R/CXCL7/PD-L1 interconnections enhances immune surveillance that inhibits the aggressiveness of TNBC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background and Purpose: Motor deficits of the ipsilateral lower limb could occur after stroke and may be associated with walking performance. This study aimed to determine whether the accuracy and movement path of targeted movement in the ipsilateral lower limb would be impaired in the chronic stage of stroke and whether this impairment would contribution to gait., Methods: Twenty adults with chronic stroke and 20 age-matched controls went through Mini Mental Status Examination (MMSE), and a series of sensorimotor tests. The targeted movement tasks were to place the big toe ipsilateral to the lesion at an external visual target (EXT) or a proprioceptive target (PRO, contralateral big toe) with eyes open (EO) or closed (EC) in a seated position. A motion analysis system was used to obtain the data for the calculation of error distance, deviation from a straight path, and peak toe-height during the targeted movement tasks and gait velocity, step length, step width and step length symmetry of the lower limb ipsilateral to the brain lesion during walking., Results: The stroke group had significantly lower MMSE and poorer visual acuity on the ipsilateral side, but did not differ in age or other sensorimotor functions when compared to the controls. For the targeted movement performance, only the deviation in PRO-EC showed significant between-group differences (p = 0.02). Toe-height in both EXT-EO and in PRO-EO was a significant predictor of step length (R2 = 0.294, p = 0.026) and step length symmetry (R2 = 0.359, p = 0.014), respectively., Discussion and Conclusions: The performance of ipsilateral lower limb targeted movement could be impaired after stroke and was associated with step length and its symmetry. The training of ipsilateral targeted movement with unseen proprioceptive target may be considered in stroke rehabilitation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Among the 14 patients with respiratory syncytial virus pneumonia, the majority (n = 8, 57.1 %) were older than 65 years and had health care-associated pneumonia (57.1 %). Over 70 % (n = 10) of them exhibited bacterial co-infection, with a high proportion (64.3 %) requiring mechanical ventilation. The hospital mortality rate was 50 %., (Copyright © 2023. Published by Elsevier B.V.)

The discrepancy between the observed lack of surface warming in the eastern equatorial Pacific and climate model projections of an El Niño-like warming pattern confronts the climate research community. While anthropogenic aerosols have been suggested as a cause, the prolonged cooling trend over the equatorial Pacific appears in conflict with Northern Hemisphere aerosol emission reduction since the 1980s. Here, using CESM, we show that the superposition of fast and slow responses to aerosol emission change-an increase followed by a decrease-can sustain the La Niña-like condition for a longer time than expected. The rapid adjustment of Hadley Cell to aerosol reduction triggers joint feedback between low clouds, wind, evaporation, and sea surface temperature in the Southeast Pacific, leading to a wedge-shaped cooling that extends to the central equatorial Pacific. Meanwhile, the northern subtropical cell gradually intensifies, resulting in equatorial subsurface cooling that lasts for decades., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: The aim of this study is to describe the management and associated follow-up strategies adopted by thyroid surgeons with different surgical volumes when loss of signal (LOS) occurred on the first side of planned bilateral thyroid surgery, and to further define the consensus on intraoperative neuromonitoring (IONM) applications., Methods: The International Neural Monitoring Study Group (INMSG) web-based survey was sent to 950 thyroid surgeons worldwide. The survey included information on the participants, IONM team/equipment/procedure, intraoperative/postoperative management of LOS, and management of LOS on the first side of thyroidectomy for benign and malignant disease., Results: Out of 950, 318 (33.5%) respondents completed the survey. Subgroup analyses were performed based on thyroid surgery volume: <50 cases/year (n = 108, 34%); 50 to 100 cases/year (n = 69, 22%); and >100 cases/year (n = 141, 44.3%). High-volume surgeons were significantly ( P  < .05) more likely to perform the standard procedures (L1-V1-R1-S1-S2-R2-V2-L2), to differentiate true/false LOS, and to verify the LOS lesion/injury type. When LOS occurs, most surgeons arrange otolaryngologists or speech consultation. When first-side LOS occurs, not all respondents decided to perform stage contralateral surgery, especially for malignant patients with severe disease (eg, extrathyroid invasion and poorly differentiated thyroid cancer)., Conclusions: Respondents felt that IONM was optimized when conducted under a collaborative team-based approach, and completed IONM standard procedures and management algorithm for LOS, especially those with high volume. In cases of first-site LOS, surgeons can determine the optimal management of disease-related, patient-related, and surgical factors. Surgeons need additional education on LOS management standards and guidelines to master their decision-making process involving the application of IONM., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Marine subsidies are vital for terrestrial ecosystems, especially low-productivity islands. However, the impact of losing these subsidies on the terrestrial food web can be difficult to predict. We analyzed 23 years of survey data from Orchid Island to assess the consequences of the abrupt loss of an important marine subsidy. After climate-driven beach erosion and predator exclusion efforts resulted in the abrupt loss of sea turtle eggs from the terrestrial food web, predatory snakes altered their foraging habitats. This increased predation on other reptile species in inland areas, resulting in population declines in most terrestrial reptile species. Comparisons with sea turtle-free locations where lizard populations remained stable supported these findings. Our study emphasizes the cascading effects of generalist predators and the unintended consequences of single-species conservation, highlighting the importance of understanding species interconnectedness and considering potential ripple effects in marine-dependent insular ecosystems.

Bioactive glass is a potential biomaterial for bone reconstruction owing to its superior bioactivity and non-toxicity. Yet, the absence of a circulatory system to carry waste and nutrients is a key issue with biomaterials implanted in the body. Thus the development of functional and vascularized new tissue requires the development of angiogenesis, which involves the formation of new blood vessels. Based on this perspective, we aimed to fabricate boron-doped 58S bioactive glass microspheres using the spray drying method, which could offer great flowability, controllable morphology, and narrow size distribution. Characterization of particle morphology and elemental composition were examined using scanning electron microscopy along with energy dispersive spectroscopy, respectively. To evaluate the effect of the boron dopant on in vitro bioactivity, X-ray diffraction and Fourier transform infrared spectroscopy were employed, while MC3T3-E1 osteoblast cells and BAOEC endothelial cells were used to assess the in vitro osteoblast and angiogenic activities, respectively. Finally, the results showed that two distinct morphologies, smooth and concave spheres, were found, with discussion of the corresponding formation mechanism. In addition, positive effects of the boron dopant were demonstrated on the in vitro bioactivity, and osteoblast and angiogenic activity when compared to the un-doped BG specimen., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The coronavirus disease (COVID-19) outbreak is a threat to adolescents' mental health and livelihoods, and lowers their subjective well-being (SWB). Expanding on previous literatures, this study examined whether internet use time was related to SWB and whether this relationship was mediated by problematic internet use (PIU) and self-esteem during the COVID-19 outbreak. In Taiwan, the COVID-19 epidemic broke out in February, 2020. During March 2 to 27, this study recruited a total of 1,060 adolescents from junior high schools by both stratified and cluster sampling, and administered a comprehensive investigation. The results displayed that SWB was significantly and negatively predicted by internet use time. PIU fully mediated the relationship. Moreover, PIU predicted a decrease of self-esteem, which played a full mediation role between PIU and SWB. The results provide evidence in explaining how increased internet use time is associated with a greater level of PIU, which relates to lower self-esteem, correlating with lower SWB in adolescents. This study can provide reference to mental health organizations and educational agencies to design appropriate SWB promotion programs for the junior high school population in terms of epidemic prevention., (© 2023. The Author(s).)

Objectives: This study examined the malleability of a tripartite cluster of purported mechanistic variables targeted in a 4-week intervention program designed to improve adults' engagement in physical activity. The targeted cluster of purported mechanisms consisted of negative views of aging (NVOA), self-efficacy beliefs, and behavioral intentions., Methods: A randomized single-blind control group design was used to implement the AgingPLUS program in a sample of middle-aged and older adults (N = 335; Mage = 60.1 years; SDage = 8.3 years; age range 45-75 years)., Results: Using an intention-to-treat approach and analyses of covariance adjusting for participants' baseline scores, findings showed significant improvements in the purported mechanistic variables both at the immediate (Week 4) and delayed posttest (Week 8) in the treatment group but not in the control group. These improvements were for the most part maintained until 8-month postrandomization, although to a smaller extent. Specifically, participants in the AgingPLUS group showed significant improvements in NVOA, self-efficacy beliefs, and behavioral intentions compared to the Health Education control group. Standardized effect sizes for statistically significant effects were variable and ranged from small (d = -0.23) to large (d = 0.80). Effect sizes showed some decay of the intervention at the 8-month posttest., Discussion: Taken together, the findings supported the efficacy of the AgingPLUS program and showed that variables representing the purported mechanisms of the intervention were significantly moved in a positive direction. In doing so, the AgingPLUS program met a major requirement of the experimental medicine approach to behavior change interventions., Clinical Trials Registration Number: NCT0329948., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Differentiated cardiomyocytes (CMs) must undergo diverse morphological and functional changes during postnatal development. However, the mechanisms underlying initiation and coordination of these changes remain unclear. Here, we delineate an integrated, time-ordered transcriptional network that begins with expression of genes for cell-cell connections and leads to a sequence of structural, cell-cycle, functional, and metabolic transitions in mouse postnatal hearts. Depletion of histone H2B ubiquitin ligase RNF20 disrupts this gene network and impairs CM polarization. Subsequently, assay for transposase-accessible chromatin using sequencing (ATAC-seq) analysis confirmed that RNF20 contributes to chromatin accessibility in this context. As such, RNF20 is likely to facilitate binding of transcription factors at the promoters of genes involved in cell-cell connections and actin organization, which are crucial for CM polarization and functional integration. These results suggest that CM polarization is one of the earliest events during postnatal heart development and provide insights into how RNF20 regulates CM polarity and the postnatal gene program., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to measure college students' coping strategies and change of lifestyle during the COVID-19 pandemic., Participants: Students from the State University in California were recruited during July 2020., Methods: A total of 11 focus group meetings were conducted., Results: Students' coping strategies were analyzed aligning with the Transactional model of stress and coping - primary appraisal, secondary appraisal and coping efforts, and meaning-based coping. Their physical activity patterns were dramatically changed. They used various ways of managing stress and tried to overcome the unexpected situation caused by COVID-19., Conclusions: This study mainly analyzed the three constructs of the transactional model: primary appraisal, secondary appraisal and coping efforts, and meaning-based coping. It is expected that the future study will focus on the last construct, coping outcomes/adaptation after the COVID-19 pandemic to measure the association between coping strategies and their outcomes.

This study aimed to identify the abnormal expression of long noncoding RNAs (lncRNAs) in T cells from patients with vitiligo and to investigate their functional roles in the immune system. Using microarray analysis, the expression levels of RNA transcripts in T cells from patients with vitiligo and controls were compared. We identified several genes and validated their expression levels in T cells from 41 vitiligo patients and 41 controls. The biological functions of the lncRNAs were studied in a transfection study using an RNA pull-down assay, followed by proteomic analysis and western blotting. The expression levels of 134 genes were significantly increased, and those of 142 genes were significantly decreased in T cells from vitiligo patients. After validation, six genes had increased expression, and three genes had decreased expression in T cells from patients with vitiligo. T-cell expression of LOC100506314 was increased in vitiligo, especially CD4+, but not CD8+ T cells. The expression levels of LOC100506314 in CD4+ T cells was positively and significantly associated with the severity of vitiligo. LOC100506314 was bound to the signal transducer and activator of transcription 3 (STAT3) and macrophage migration inhibitory factor (MIF). Enhanced expression of LOC100506314 inhibited the phosphorylation of STAT3, protein kinase B (AKT), and extracellular signal-regulated protein kinases (ERK), as well as the levels of nuclear protein of p65 and the expression of IL-6 and IL-17 in Jurkat cells and T cells from patients with vitiligo. In conclusion, this study showed that the expression of LOC100506314 was elevated in CD4+ T cells from patients with vitiligo and associated the severity of vitiligo. LOC100506314 interacted with STAT3 and MIF and inhibited IL-6 and IL-17 expression by suppressing the STAT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κ B), AKT, and ERK pathways. Enhanced expression of LOC100506314 in T cells may be a potential treatment strategy for vitiligo., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ning-Sheng Lai et al.)

Clostridioides difficile spores are considered as the major source responsible for the development of C . difficile infection (CDI), which is associated with an increased risk of death in patients and has become an important issue in infection control of nosocomial infections. Current treatment against CDI still relies on antibiotics, which also damage normal flora and increase the risk of CDI recurrence. Therefore, alternative therapies that are more effective against C . difficile bacteria and spores are urgently needed. Here, we designed an oxidation process using H 2 O 2 containing PBS solution to generate Cl - and peroxide molecules that further process Ag and Au ions to form nanoboxes with Ag-Au peroxide coat covering Au shell and AgCl core (AgAu-based nanoboxes). The AgAu-based nanoboxes efficiently disrupted the membrane structure of bacteria/spores of C . difficile after 30-45 min exposure to the highly reactive Ag/Au peroxide surface of the nano structures. The Au-enclosed AgCl provided sustained suppression of the growth of 2 × 10 7 pathogenic Escherichia coli for up to 19 days. In a fecal bench ex vivo test and in vivo CDI murine model, biocompatibility and therapeutic efficacy of the AuAg nanoboxes to attenuate CDI was demonstrated by restoring the gut microbiota and colon mucosal structure. The treatment successfully rescued the CDI mice from death and prevented their recurrence mediated by vancomycin treatment. The significant outcomes indicated that the new peroxide-derived AgAu-based nanoboxes possess great potential for future translation into clinical application as a new alternative therapeutic strategy against CDI., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of The American Institute of Chemical Engineers.)

Major depressive disorder (MDD), a common psychiatric condition, adversely affects patients' moods and quality of life. Despite the development of various treatments, many patients with MDD remain vulnerable and inadequately controlled. Since anhedonia is a feature of depression and there is evidence of leading to metabolic disorder, deep brain stimulation (DBS) to the nucleus accumbens (NAc) might be promising in modulating the dopaminergic pathway. To determine whether NAc-DBS alters glucose metabolism via mitochondrial alteration and neurogenesis and whether these changes increase neural plasticity that improves behavioral functions in a chronic social defeat stress (CSDS) mouse model. The Lab-designed MR-compatible neural probes were implanted in the bilateral NAc of C57BL/6 mice with and without CSDS, followed by DBS or sham stimulation. All animals underwent open-field and sucrose preference testing, and brain resting-state functional MRI analysis. Meanwhile, we checked the placement of neural probes in each mouse by T2 images. By confirming the placement location, mice with incorrect probe placement (the negative control group) showed no significant therapeutic effects in behavioral performance and functional connectivity (FC) after receiving electrical stimulation and were excluded from further analysis. Western blotting, seahorse metabolic analysis, and electron microscopy were further applied for the investigation of NAc-DBS. We found NAc-DBS restored emotional deficits in CSDS-subjected mice. Concurrent with behavioral amelioration, the CSDS DBS-on group exhibited enhanced FC in the dopaminergic pathway with increased expression of BDNF- and NeuN-positive cells increased dopamine D1 receptor, dopamine D2 receptors, and TH in the medial prefrontal cortex, NAc, ventral hippocampus, ventral tegmental area, and amygdala. Increased p AMPK/total AMPK and PGC-1α levels, functions of oxidative phosphorylation, and mitochondrial biogenesis were also observed after NAc-DBS treatment. Our findings demonstrate that NAc-DBS can promote BDNF expression, which alters FC and metabolic profile in the dopaminergic pathway, suggesting a potential strategy for ameliorating emotional processes in individuals with MDD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Inc.)

Background: Insomnia and frailty are prevalent in older adults. This study aimed to elucidate the impact of insomnia and sedative-hypnotic use on the frailty rate over time., Methods: We used data from community-dwelling older adults (mean ± SD age = 69.4 ± 8.2 years) from the Healthy Aging Longitudinal Study in Taiwan (HALST). A total of 4,744 participants were included in the study and were followed up for an average of 3.2 years. Frailty was assessed using the Fried criteria. Self-reported sleep problems, sedative-hypnotic use, and claims records from the National Health Insurance database were used. The generalized equation estimation (GEE) approach was applied to account for correlations between repeated measures. The average impact of insomnia and drug use on frailty over time was estimated by adjusting for potential confounding factors using the logic link in the GEE approach., Results: The adjusted odds ratio (OR) of frailty was 1.41 (95% CI: [1.16, 1.72], Z-test statistics Z = 3.39, p <0.001) for insomnia and 1.52 ([1.16, 2.00], Z = 3.00, p = 0.0027) for sedative-hypnotic use. Interactions between insomnia and sedative-hypnotic use with frailty were not statistically significant. Long sleep duration > 8 hours, daytime sleepiness, and sleep apnea was also associated with an increased likelihood of developing frailty. Notably, a dose-response relationship between sedative-hypnotic drug use and frailty was observed., Conclusions: Insomnia and sedative-hypnotic use were independently associated with increased frailty. The implementation of nonpharmacological treatments to attenuate insomnia may reduce frailty rates., (Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Nanofibrous membranes made of hydrogels have high specific surface areas and are suitable as drug carriers. Multilayer membranes fabricated by continuous electrospinning could delay drug release by increasing diffusion pathways, which is beneficial for long-term wound care. In this experiment, polyvinyl alcohol (PVA) and gelatin were used as membrane substrates, and a sandwich PVA/gelatin/PVA structure of layer-by-layer membranes was prepared by electrospinning under different drug loading concentrations and spinning times. The outer layers on both sides were citric-acid-crosslinked PVA membranes loaded with gentamicin as an electrospinning solution, and the middle layer was a curcumin-loaded gelatin membrane for the study of release behavior, antibacterial activity, and biocompatibility. According to the in vitro release results, the multilayer membrane could release curcumin slowly; the release amount was about 55% less than that of the single layer within 4 days. Most of the prepared membranes showed no significant degradation during immersion, and the phosphonate-buffered saline absorption rate of the multilayer membrane was about five to six times its weight. The results of the antibacterial test showed that the multilayer membrane loaded with gentamicin had a good inhibitory effect on Staphylococcus aureus and Escherichia coli . In addition, the layer-by-layer assembled membrane was non-cytotoxic but detrimental to cell attachment at all gentamicin-carrying concentrations. This feature could be used as a wound dressing to reduce secondary damage to the wound when changing the dressing. This multilayer wound dressing could be applied to wounds in the future to reduce the risk of bacterial infection and help wounds heal.

Aim: This study examined the relationships between stress, excessive drinking, including binge and heavy drinking, and health insurance status among a regionally representative sample of adults living in Northern Larimer County, Colorado, during the COVID-19 pandemic., Subject and Methods: Data from 551 adults aged 18 to 64 years (62.98% aged 45 to 65 years; 73.22% female; 92.98% non-Hispanic White) were used. The sample was weighted by age and binary sex. A series of logistic regressions were applied to examine bivariate associations among stress, drinking, and health insurance status, with and without accounting for the effects of sociodemographic and health-related covariates. Stratified analyses were applied to explore differential associations of stress and drinking among individuals with different health insurance coverage., Results: A total of 23.23% of the adult sample reported binge drinking, and 16.15% reported heavy drinking; 10.53% of the sample reported both binge and heavy drinking. Individuals with higher levels of stress were more likely to report binge drinking (OR: 1.65; 95% CI: 1.65, 1.68) and heavy drinking (OR: 2.61; 95% CI: 2.54, 2.67), after adjusting for sociodemographic and health-related covariates. Relative to individuals with private health insurance coverage, adults enrolled in Medicaid and those without health insurance coverage were more susceptible to the effect of stress on binge and heavy drinking., Conclusion: Our results highlighted a need for continuing statewide and/or national efforts in closing the insurance coverage gap and providing affordable marketplace health insurance in the hope of preventing excessive drinking due to high levels of stress during a challenging time., Competing Interests: Conflict of interestAll authors declare that they have no conflicts of interest., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

This article updates and extends an earlier meta-analysis (Westerhof et al., 2014) on the longitudinal effects of subjective aging (SA) on health outcomes. A systematic search in different databases (APA PsycInfo, PubMed, Web of Science, and Scopus) resulted in 99 articles, reporting on 107 studies. Participants: Studies had a median sample size of 1,863 adults with a median age of 66 years. A randomized effect meta-analysis showed a significant, small effect (likelihood ratio = 1.347; 95% confidence interval [1.300, 1.396]; p < .001), similar in magnitude to the previous meta-analysis of 19 studies. Although the results showed high heterogeneity in the longitudinal link between SA and health outcomes, there were no differences in effects according to chronological age of participants, welfare state status (more or less developed social security system), length of follow-up, type of health-related outcome, or quality of the study. Effects were stronger for multiitem measures of self-perceptions of aging than for the frequently used single-item measures assessing subjective age, especially for indicators of physical health. Based on this meta-analysis, building on five times more studies than the 2014 review, we consider the associations of measures of SA with health and longevity across time as robust, albeit small in size. Future research should concentrate on the clarification of pathways mediating the relation between SA and health outcomes, as well as potential bidirectional effects. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background and Aims: Hepatorenal syndrome (HRS) is a disastrous renal complication of advanced liver disease with a poor prognosis. Restoring normal liver function through liver transplantation (LT) is a standardized treatment with favorable short-term survival. However, the long-term renal outcomes in patients with HRS receiving living donor LT (LDLT) are controversial. This study aimed to investigate the prognostic impact of LDLT in patients with HRS., Methods: We reviewed adult patients who underwent LDLT between July 2008 and September 2017. Recipients were classified into 1) HRS type 1 (HRS1, N  = 11), 2) HRS type 2 (HRS2, N  = 19), 3) non-HRS recipients with pre-existing chronic kidney disease (CKD, N  = 43), and 4) matched normal renal function ( N  = 67)., Results: Postoperative complications and 30-day surgical mortality were comparable among the HRS1, HRS2, CKD, and normal renal function groups. The 5-year survival rate was >90% and estimated glomerular filtration rate (eGFR) transiently improved and peaked at 4 weeks post-transplantation in patients with HRS. However, renal function deteriorated and resulted in CKD stage ≥ III in 72.7% of HRS1 and 78.9% of HRS2 patients (eGFR <60 ml/min/1.73 m 2 ). The incidence of developing CKD and end-stage renal disease (ESRD) was similar between the HRS1, HRS2, and CKD groups, but significantly higher than that in the normal renal function group (both P  < 0.001). In multivariate logistic regression, pre-LDLT eGFR <46.4 ml/min/1.73 m 2 predicted the development of post-LDLT CKD stage ≥ III in patients with HRS (AUC = 0.807, 95% CI = 0.617-0.997, P  = 0.011)., Conclusions: LDLT provides a significant survival benefit for patients with HRS. However, the risk of CKD stage ≥ III and ESRD among patients with HRS was similar to that in pre-transplant CKD recipients. An early preventative renal-sparing strategy in patients with HRS is recommended., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Tseng, Lin, Lin, Chen, Yong, Lin, Wang and Chan.)

A series of electrospun polyvinyl alcohol (PVA) fiber membranes were crosslinked with citric acid (CA) at concentrations of 10, 20, and 30 wt.% (designated as CA10, CA20, and CA30). The effects of CA on the chemical structure, mechanical strength, swelling resistance, and cytotoxicity of the crosslinked PVA fibrous membranes were investigated. Infrared spectroscopy indicated the enhanced esterification of carboxyl and hydroxyl groups between CA and PVA. The modulus and strength of the electrospun PVA membrane increased due to the crosslinking between CA and PVA. The crosslinking of the PVA fiber matrix with CA increased the PVA binding point, thereby increasing the swelling resistance and modulus; however, the concentration of CA used was limited. Results showed that the water absorption of the PVA membranes decreased from 6.58 ± 0.04 g/g for CA10 to 3.56 ± 3.33 g/g for CA20 and 2.85 ± 0.40 g/g for CA30 with increasing CA. The water absorption remained unchanged after the membrane was soaked for a period of time, so no significant difference was found in the water absorption capacity of the same group after immersion from 1 h to 3 d. The tensile strength increased from 20.52 MPa of CA10 to 22.09 MPa of CA20. With an increased amount of CA used for crosslinking, the tensile strength and modulus of CA30 decreased to 11.48 and 13.94 MPa, respectively. Our study also showed that CA was not toxic to L929 cell viability when used for fiber crosslinking at less than 20 wt.% PVA, meaning it may be a good candidate as a support layer for guided tissue engineering.

Photography is an art form where integration of the human visual perception and psychological experiences result in aesthetic pleasure. This research utilizes eye tracking to explore the impact of the properties of Gestalt in photography on people's visual cognitive process in order to understand the psychological processes and patterns of photography appreciation. This study found that images with Gestalt qualities can significantly affect fixation, sightline distribution, and subjective evaluation of aesthetics and complexity. Closure composition images seem to make cognition simpler, resulting in the least number of fixation and saccades, longer fixation duration, and more concentrated sightline indicating stronger feeling of beauty, while images which portray similarity results in the greatest fixation and saccades, longest saccade duration, and greater scattering of sightline, indicating feelings of complexity and unsightliness. The results of this research are closely related to the theories of art and design, and have reference value for photography theory and application., Competing Interests: The author(s) declare(s) that the contents of the article are in agreement with the ethics described in http://biblio.unibe.ch/portale/elibrary/BOP/jemr/ethics.html and that there is no conflict of interest regarding the publication of this paper., (Copyright (©) 2023 Hsien-Chih Chuang, Han-Yi Tseng, Da-Lun Tang.)

Increasing requirements for neural implantation are helping to expand our understanding of nervous systems and generate new developmental approaches. It is thanks to advanced semiconductor technologies that we can achieve the high-density complementary metal-oxide-semiconductor electrode array for the improvement of the quantity and quality of neural recordings. Although the microfabricated neural implantable device holds much promise in the biosensing field, there are some significant technological challenges. The most advanced neural implantable device relies on complex semiconductor manufacturing processes, which are required for the use of expensive masks and specific clean room facilities. In addition, these processes based on a conventional photolithography technique are suitable for mass production, which is not applicable for custom-made manufacturing in response to individual experimental requirements. The microfabricated complexity of the implantable neural device is increasing, as is the associated energy consumption, and corresponding emissions of carbon dioxide and other greenhouse gases, resulting in environmental deterioration. Herein, we developed a fabless fabricated process for a neural electrode array that was simple, fast, sustainable, and customizable. An effective strategy to produce conductive patterns as the redistribution layers (RDLs) includes implementing microelectrodes, traces, and bonding pads onto the polyimide (PI) substrate by laser micromachining techniques combined with the drop coating of the silver glue to stack the laser grooving lines. The process of electroplating platinum on the RDLs was performed to increase corresponding conductivity. Sequentially, Parylene C was deposited onto the PI substrate to form the insulation layer for the protection of inner RDLs. Following the deposition of Parylene C, the via holes over microelectrodes and the corresponding probe shape of the neural electrode array was also etched by laser micromachining. To increase the neural recording capability, three-dimensional microelectrodes with a high surface area were formed by electroplating gold. Our eco-electrode array showed reliable electrical characteristics of impedance under harsh cyclic bending conditions of over 90 degrees. For in vivo application, our flexible neural electrode array demonstrated more stable and higher neural recording quality and better biocompatibility as well during the 2-week implantation compared with those of the silicon-based neural electrode array. In this study, our proposed eco-manufacturing process for fabricating the neural electrode array reduced 63 times of carbon emissions compared to the traditional semiconductor manufacturing process and provided freedom in the customized design of the implantable electronic devices as well.

Owing to its capacity to eliminate a long-standing methodological limitation, fiber photometry can assist research gaining novel insight into neural systems. Fiber photometry can reveal artifact-free neural activity under deep brain stimulation (DBS). Although evoking neural potential with DBS is an effective method for mediating neural activity and neural function, the relationship between DBS-evoked neural Ca 2+ change and DBS-evoked neural electrophysiology remains unknown. Therefore, in this study, a self-assembled optrode was demonstrated as a DBS stimulator and an optical biosensor capable of concurrently recording Ca 2+ fluorescence and electrophysiological signals. Before the in vivo experiment, the volume of tissue activated (VTA) was estimated, and the simulated Ca 2+ signals were presented using Monte Carlo (MC) simulation to approach the realistic in vivo environment. When VTA and the simulated Ca 2+ signals were combined, the distribution of simulated Ca 2+ fluorescence signals matched the VTA region. In addition, the in vivo experiment revealed a correlation between the local field potential (LFP) and the Ca 2+ fluorescence signal in the evoked region, revealing the relationship between electrophysiology and the performance of neural Ca 2+ concentration behavior. Concurrent with the VTA volume, simulated Ca 2+ intensity, and the in vivo experiment, these data suggested that the behavior of neural electrophysiology was consistent with the phenomenon of Ca 2+ influx to neurons.

Background: Liver cancer is ranked fifth in incidence and second in mortality among cancers in Taiwan. Nevertheless, the Taiwan government does not screen for liver cancer in its free cancer screening and preventive health examination service. This study compared the differences in cancer stage and survival between patients who received an initial liver cancer diagnosis in outpatient departments (OPDs) and those who received such a diagnosis in emergency departments (EDs)., Methods: This retrospective cohort study used the 2000-2016 National Health Insurance Database to obtain a sample from 2 million Taiwanese residents. To evaluate the effect of the utilization of the adult health examination offered to people aged ≥ 40 years, patients aged ≥ 40 years who received an initial liver cancer diagnosis between 2003 and 2015 were followed up until December 31, 2016., Results: In total, 2,881 patients were included in this study. A greater proportion of cancer cases in the OPD group were non-advanced than those in the ED group (75.26% vs. 54.23%). Having stage C or D cancer, having a low monthly salary, and a Charlson comorbidity index score ≥ 8, not having hepatitis B, being divorced, and attending a non-public hospital as the primary care institution were risk factors for initial ED diagnosis. The risk of liver cancer-specific death among the ED group patients was 1.38 times that among the OPD group patients (adjusted hazard ratio = 1.38, 95% confidence interval [CI] = 1.14-1.68, P < 0.001). However, the use of health examination did not exert a significant effect on the likelihood of liver cancer diagnosis in an ED (adjusted odds ratio = 0.86, 95% CI = 0.61-1.21, P = 0.381)., Conclusion: Government-subsidized health examinations are insufficient to prevent first-ever diagnosed liver cancers in EDs. Patients with liver cancers diagnosed in EDs had a higher risk of advanced stage and mortality. For early detection and treatment, the government may consider implementing liver cancer screening for high-risk and low-socioeconomic people., (© 2023. The Author(s).)

Alien species may pose substantial impacts on biodiversity around the globe through international trade and travel. A niche shift hypothesis was proposed to explain the adaptive change of alien or invasive species in new habitats. However, whether niche shifts occur in alien species likely depends on both characteristics inherent to the species itself and its original distribution. Here we identified a newly exotic trap-jaw ant ( Odontomachus troglodytes ) in Taiwan by morphological and phylogenetic analyses. The possible distribution range and the niche shift pattern were evaluated using ecological niche modelling. The results indicated that exotic O. troglodytes in the newly distributed area displayed a significant niche shift with low niche overlap and high niche expansion. This study reveals a long-distance invasive event from central Africa to Southeast Asia (more than 10,000 km) and predicts the potential distribution range of this new alien species in Taiwan., Competing Interests: The authors declare there are no competing interests., (©2023 Lin et al.)

The death triad, including coagulopathy, hypothermia, and acidosis, is shown to be a strong predictor of mortality in trauma patients. We aimed to investigate whether the inclusion of hypotension, defined as systolic blood pressure (SBP) < 60 mmHg, as a fourth factor in the death triad would comprise a death tetrad to help stratify mortality risk in trauma patients. A total of 3361 adult trauma patients between 1 January 2009 and 31 December 2019 were allocated into groups to investigate whether hypotension matters in determining the mortality outcome of trauma patients who possess 1−3 death triad components compared to those without any component. Hypotension was added to the death tetrad, and the adjusted mortality outcome was compared among groups with 0−4 death tetrad components. Herein, we showed that SBP < 60 mmHg could be used to identify patients at risk of mortality among patients with one or two death triad components. Patients with one, two, and three death tetrad components had respective adjusted mortality rates of 3.69-, 10.10-, and 40.18-fold, determined by sex, age, and comorbidities. The mortality rate of trauma patients with all the four death tetrad components was 100%. The study suggested that hypotension, defined as an SBP < 60 mmHg, may act as a proper death tetrad component to stratify the mortality risk of trauma patients.

In thyroid and parathyroid surgery, surgical energy devices (SEDs) provide more efficient hemostasis than conventional clamp-and-tie hemostasis in areas with rich blood supply. However, when a SED is activated near the recurrent laryngeal nerve (RLN), the heat generated by the SED may injure the nerve irreversibly. To safely apply SEDs in thyroid/parathyroid surgery, this article introduces experimental porcine model studies to investigate the activation and cooling safety parameters of SEDs in standardized electrophysiological (EP) and thermographic (TG) procedures, respectively. In the EP safety parameter experiments, continuous intraoperative neuromonitoring (C-IONM) is applied to demonstrate the RLN function in real-time. The EP activation study evaluates the safe activation distance of SEDs; the EP cooling study evaluates the safe cooling time of SEDs. In the TG safety parameter experiment, a thermal imaging camera is used to record the temperature change after activating the SED. The TG activation study evaluates the lateral thermal spread distance after SED activation in a dry or humid environment and whether smoke and splashing are generated; the TG cooling study evaluates the cooling time. This will help establish the safety parameters of newly developed SEDs used in thyroid/parathyroid surgery and provide safety guidelines to avoid RLN injury and related complications.

Background and Objectives: Ankylosing spondylitis (AS) is a chronic inflammatory disease and is highly linked with the expression of the human leukocytic antigen-B*27 (HLA-B*27) genotype. HLA-B*27 heavy chain (B*27-HC) has an innate characteristic to slowly fold, resulting in the accumulation of the misfolded B*27-HC and the formation of homo-oligomeric B*27-HC molecules. The homo-oligomeric B*27-HC can act as a ligand of KIR3DL2. Interaction of the homo-oligomeric B*27-HC molecules with KIR3DL2 will trigger the survival and activation of KIR3DL2-positive NK cells. However, the effects of homo-oligomeric B*27-HC molecules associated with KIR3DL2 on the cytotoxic activity of NK cells and their cytokine expressions remain unknown. Materials and Methods: HLA-B*-2704-HC was overexpressed in the HMy2.C1R (C1R) cell line. Western blotting and quantitative RT-PCR were used to analyze the protein expression and cytokine expression, respectively, when C1R-B*-2704 cells that overexpress B*2704-HC were co-cultured with NK-92MI cells. Flow cytometry was used to analyze the cytotoxicity mediated by NK-92MI cells. Results: Our results revealed that NK-92MI cells up-regulated the expression of perforin and enhanced the cytotoxic activity via augmentation of PI3K/AKT signaling after co-culturing with C1R-B*2704 cells. Suppression of the dimerized B*27-HC formation or treatment with an inhibitor of PI3K, LY294002, or with an anti-B*27-HC monoclonal antibody can reduce the perforin expression of NK-92MI after co-culturing with C1R-B*-2704. Co-culturing with C1R-B*-2704 cells suppressed the TNF-α and IL6 expressions of NK-92MI cells. Conclusion: Stimulation of NK cell-mediated cytotoxicity by homo-oligomeric B*27-HC molecules may contribute to the pathogenesis of AS.

CXCR4 antagonists have been claimed to reduce mortality after myocardial infarction in myocardial infarction (MI) animals, presumably due to suppressing inflammatory responses caused by myocardial ischemia-reperfusion injury, thus, subsequently facilitating tissue repair and cardiac function recovery. This study aims to determine whether a newly designed CXCR4 antagonist DBPR807 could exert better vascular-protective effects than other clinical counterparts (e.g., AMD3100) to alleviate cardiac damage further exacerbated by reperfusion. Consequently, we find that instead of traditional continuous treatment or multiple-dose treatment at different intervals of time, a single-dose treatment of DBPR807 before reperfusion in MI animals could attenuate inflammation via protecting oxidative stress damage and preserve vascular/capillary density and integrity via mobilizing endothelial progenitor cells, leading to a desirable fibrosis reduction and recovery of cardiac function, as evaluated with the LVEF (left ventricular ejection fraction) in infarcted hearts in rats and mini-pigs, respectively. Thus, it is highly suggested that CXCR4 antagonists should be given at a single high dose prior to reperfusion to provide the maximal cardiac functional improvement. Based on its favorable efficacy and safety profiles indicated in tested animals, DBPR807 has a great potential to serve as an adjunctive medicine for percutaneous coronary intervention (PCI) therapies in acute MI patients.

The development of multidrug resistance (MDR) is one of the major challenges in the treatment of cancer which is caused by the overexpression of the ATP-binding cassette (ABC) transporters ABCB1 (P-glycoprotein) and/or ABCG2 (BCRP/MXR/ABCP) in cancer cells. These transporters are capable of reducing the efficacy of cytotoxic drugs by actively effluxing them out of cancer cells. Since there is currently no approved treatment for patients with multidrug-resistant tumors, the drug repurposing approach provides an alternative route to identify agents to reverse MDR mediated by ABCB1 and/or ABCG2 in multidrug-resistant cancer cells. WDR5-0103 is a histone H3 lysine 4 (H3K4) methyltransferase inhibitor that disrupts the interaction between the WD repeat-containing protein 5 (WDR5) and mixed-lineage leukemia (MLL) protein. In this study, the effect of WDR5-0103 on MDR mediated by ABCB1 and ABCG2 was determined. We found that in a concentration-dependent manner, WDR5-0103 could sensitize ABCB1- and ABCG2-overexpressing multidrug-resistant cancer cells to conventional cytotoxic drugs. Our results showed that WDR5-0103 reverses MDR and improves drug-induced apoptosis in multidrug-resistant cancer cells by inhibiting the drug-efflux function of ABCB1 and ABCG2, without altering the protein expression of ABCB1 or ABCG2. The potential sites of interactions of WDR5-0103 with the drug-binding pockets of ABCB1 and ABCG2 were predicted by molecular docking. In conclusion, the MDR reversal activity of WDR5-0103 demonstrated here indicates that it could be used in combination therapy to provide benefits to a subset of patients with tumor expressing high levels of ABCB1 or ABCG2., Competing Interests: Conflict of interest statement The authors have no conflict of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Intraoperative facial nerve monitoring (FNM) has been widely accepted as an adjunct during parotid surgery to facilitate identification of the facial nerve (FN) main trunk, dissection of FN branches, confirmation of FN function integrity, detection of FN injury and prognostication of facial expression after tumor resection. Although the use of FNM in parotidectomy is increasing, little uniformity exists in its application from the literature. Thus, not only are the results of many studies difficult to compare but the value of FNM technology is also limited. The article reviews the current literature and proposes our standardized FNM procedures during parotid surgery, such as standards in FNM setup, standards in general anesthesia, standards in FNM procedures and application of stimulus currents, interpretation of electrophysiologic signals and prediction of the facial expression outcome and pre-/post-operative assessment of facial expressions. We hope that the FNM standardized procedures will provide greater uniformity, improve the quality of applications and contribute to future research.

Background: Periodontal disease is a chronic inflammatory disease. Given its high prevalence, especially in aging population, the detailed mechanisms about pathogenesis of periodontal disease are important issues for study. Neutrophil firstly infiltrates to periodontal disease-associated pathogen loci and amplifies the inflammatory response for host defense. However, excessive neutrophil-secreted neutrophil elastase (NE) damages the affected gingival. In lung and esophageal epithelium, NE had been proved to upregulate several growth factors including placenta growth factor (PGF). PGF is an angiogenic factor with proinflammatory properties, which mediates the progression of inflammatory disease. Therefore, we hypothesize excessive NE upregulates PGF and participates in the pathogenesis and progression of periodontal disease., Methods: In gingival epithelial cells (GEC), growth factors array demonstrated NE-increased growth factors and further be corroborated by Western blot assay and ELISA. The GEC inflammation was evaluated by ELISA. In mice, the immunohistochemistry results demonstrated ligature implantation-induced neutrophil infiltration and growth factor upregulation. By multiplex assay, the ligature-induced proinflammatory cytokines level in gingival crevicular fluid (GCF) were evaluated. Finally, alveolar bone absorption was analyzed by micro-CT images and H & E staining., Results: NE upregulated PGF expression and secretion in GEC. PGF promoted GEC to secret IL-1β, IL-6, and TNF-α in GCF In periodontal disease animal model, ligature implantation triggered NE infiltration and PGF expression. Blockade of PGF attenuated the ligature implantation-induced IL-1β, IL-6, TNF-α and MIP-2 secretion and ameliorated the alveolar bone loss in mice., Conclusion: In conclusion, the NE-induced PGF triggers gingival epithelium inflammation and promotes the pathogenesis and progression of periodontal disease., (© 2021 American Academy of Periodontology.)