Discovery of a mu-opioid receptor modulator that in combination with morphinan antagonists induces analgesia.

Morphinan antagonists, which block opioid effects at mu-opioid receptors, have been studied for their analgesic potential. Previous studies have suggested that these antagonists elicit analgesia with fewer adverse effects in the presence of the mutant mu-opioid receptor (MOR; S196A). However, introducing a mutant receptor for medical applications represents significant challenges. We hypothesize that binding a chemical compound to the MOR may elicit a comparable effect to the S196A mutation. Through high-throughput screening and structure-activity relationship studies, we identified a modulator, 4-(2-(4-fluorophenyl)-4-oxothiazolidin-3-yl)-3-methylbenzoic acid (BPRMU191), which confers agonistic properties to small-molecule morphinan antagonists, which induce G protein-dependent MOR activation. Co-application of BPRMU191 and morphinan antagonists resulted in MOR-dependent analgesia with diminished side effects, including gastrointestinal dysfunction, antinociceptive tolerance, and physical and psychological dependence. Combining BPRMU191 and morphinan antagonists could serve as a potential therapeutic strategy for severe pain with reduced adverse effects and provide an avenue for studying G protein-coupled receptor modulation.

CXCR7 activation evokes the anti-PD-L1 antibody against glioblastoma by remodeling CXCL12-mediated immunity.

The interaction between glioblastoma cells and glioblastoma-associated macrophages (GAMs) influences the immunosuppressive tumor microenvironment, leading to ineffective immunotherapies. We hypothesized that disrupting the communication between tumors and macrophages would enhance the efficacy of immunotherapies. Transcriptomic analysis of recurrent glioblastoma specimens indicated an enhanced neuroinflammatory pathway, with CXCL12 emerging as the top-ranked gene in secretory molecules. Single-cell transcriptome profiling of naïve glioblastoma specimens revealed CXCL12 expression in tumor and myeloid clusters. An analysis of public glioblastoma datasets has confirmed the association of CXCL12 with disease and PD-L1 expression. In vitro studies have demonstrated that exogenous CXCL12 induces pro-tumorigenic characteristics in macrophage-like cells and upregulated PD-L1 expression through NF-κB signaling. We identified CXCR7, an atypical receptor for CXCL12 predominantly present in tumor cells, as a negative regulator of CXCL12 expression by interfering with extracellular signal-regulated kinase activation. CXCR7 knockdown in a glioblastoma mouse model resulted in worse survival outcomes, increased PD-L1 expression in GAMs, and reduced CD8+ T-cell infiltration compared with the control group. Ex vivo T-cell experiments demonstrated enhanced cytotoxicity against tumor cells with a selective CXCR7 agonist, VUF11207, reversing GAM-induced immunosuppression in a glioblastoma cell-macrophage-T-cell co-culture system. Notably, VUF11207 prolonged survival and potentiated the anti-tumor effect of the anti-PD-L1 antibody in glioblastoma-bearing mice. This effect was mitigated by an anti-CD8ß antibody, indicating the synergistic effect of VUF11207. In conclusion, CXCL12 conferred immunosuppression mediated by pro-tumorigenic and PD-L1-expressing GAMs in glioblastoma. Targeted activation of glioblastoma-derived CXCR7 inhibits CXCL12, thereby eliciting anti-tumor immunity and enhancing the efficacy of anti-PD-L1 antibodies.

Web-based artificial intelligence to predict cognitive impairment following stroke: A multicenter study.

BACKGROUND AND PURPOSE: Post-stroke cognitive impairment (PSCI) is highly prevalent in modern society. However, there is limited study implying an accurate and explainable machine learning model to predict PSCI. The aim of this study is to develop and validate a web-based artificial intelligence (AI) tool for predicting PSCI. METHODS: The retrospective cohort study design was conducted to develop and validate a web-based prediction model. Adults who experienced a stroke between January 1, 2004, and September 30, 2017, were enrolled, and patients with PSCI were followed up from the stroke index date until their last follow-up. The model's performance metrics, including accuracy, area under the curve (AUC), recall, precision, and F1 score, were compared. RESULTS: A total of 3209 stroke patients were included in the study. The model demonstrated an accuracy of 0.8793, AUC of 0.9200, recall of 0.6332, precision of 0.9664, and F1 score of 0.7651. In the external validation phase, the accuracy improved to 0.9039, AUC to 0.9094, recall to 0.7457, precision to 0.9168, and F1 score to 0.8224. The final model can be accessed at https://psci-calculator.my.id/. CONCLUSION: Our results are able to produce a user-friendly interface that is useful for health practitioners to perform early prediction on PSCI. These findings also suggest that the provided AI model is reliable and can serve as a roadmap for future studies using AI models in a clinical setting.

Effectiveness of Acupressure for Fatigue Alleviation in Patients Receiving Hemodialysis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Fatigue, a major health concern among patients receiving hemodialysis, is associated with poor quality of life, negative emotions, and cognitive dysfunction. Acupressure is a low-cost and noninvasive traditional Chinese therapy that has been widely used in community and clinic settings. However, the beneficial effects of acupressure on various aspects of fatigue among these patients have not been systematically investigated. PURPOSE: This study was designed to determine the effects of acupressure on fatigue in patients receiving hemodialysis. The moderating influences of bio-sociodemographic characteristics and methodology on the association between acupressure and posthemodialysis fatigue were also examined. METHODS: Four electronic databases were searched for qualified articles published between database inception and November 2, 2022. Only randomized controlled trials designed to investigate the effects of acupressure on fatigue in patients receiving hemodialysis were qualified for consideration. A random-effects model was used for data analysis. RESULTS: Eight randomized controlled trials with 11 effect sizes and 725 participants were included in this study. In these studies, acupressure was found to have a significantly higher alleviation effect on general fatigue (g = -0.78; 95% confidence interval [-1.09, -0.48]) and the behavioral, emotional, sensory, and cognitive domains of fatigue (g = -0.51, -0.51, -0.72, and -0.41, respectively) among patients receiving hemodialysis than those in the control groups. Furthermore, the stimulation of the Shenmen acupoint was found to increase the effects (p < .01) of acupressure on fatigue reduction significantly. Notably, the use of special equipment to perform the acupressure was not found to significantly improve outcomes (p = .99). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Acupressure is effective in alleviating fatigue in patients receiving hemodialysis, particularly when the Shenmen acupoint is used together with other acupoints, and is effective without the application of special equipment. Acupressure may be adopted as a complementary therapy for fatigue alleviation in patients receiving hemodialysis. Based on the findings, healthcare providers should coach patients receiving hemodialysis with fatigue on how to use acupressure therapy appropriately to alleviate this health concern.

White matter alterations and their associations with biomarkers and behavior in subjective cognitive decline individuals: a fixel-based analysis.

BACKGROUND: Subjective cognitive decline (SCD) is an early stage of dementia linked to Alzheimer's disease pathology. White matter changes were found in SCD using diffusion tensor imaging, but there are known limitations in voxel-wise tensor-based methods. Fixel-based analysis (FBA) can help understand changes in white matter fibers and how they relate to neurodegenerative proteins and multidomain behavior data in individuals with SCD. METHODS: Healthy adults with normal cognition were recruited in the Northeastern Taiwan Community Medicine Research Cohort in 2018-2022 and divided into SCD and normal control (NC). Participants underwent evaluations to assess cognitive abilities, mental states, physical activity levels, and susceptibility to fatigue. Neurodegenerative proteins were measured using an immunomagnetic reduction technique. Multi-shell diffusion MRI data were collected and analyzed using whole-brain FBA, comparing results between groups and correlating them with multidomain assessments. RESULTS: The final enrollment included 33 SCD and 46 NC participants, with no significant differences in age, sex, or education between the groups. SCD had a greater fiber-bundle cross-section than NC (pFWE < 0.05) at bilateral frontal superior longitudinal fasciculus II (SLFII). These white matter changes correlate negatively with plasma Aß42 level (r = -0.38, p = 0.01) and positively with the AD8 score for subjective cognitive complaints (r = 0.42, p = 0.004) and the Hamilton Anxiety Rating Scale score for the degree of anxiety (Ham-A, r = 0.35, p = 0.019). The dimensional analysis of FBA metrics and blood biomarkers found positive correlations of plasma neurofilament light chain with fiber density at the splenium of corpus callosum (pFWE < 0.05) and with fiber-bundle cross-section at the right thalamus (pFWE < 0.05). Further examination of how SCD grouping interacts between the correlations of FBA metrics and multidomain assessments showed interactions between the fiber density at the corpus callosum with letter-number sequencing cognitive score (pFWE < 0.01) and with fatigue to leisure activities (pFWE < 0.05). CONCLUSION: Based on FBA, our investigation suggests white matter structural alterations in SCD. The enlargement of SLFII's fiber cross-section is linked to plasma Aß42 and neuropsychiatric symptoms, which suggests potential early axonal dystrophy associated with Alzheimer's pathology in SCD. The splenium of the corpus callosum is also a critical region of axonal degeneration and cognitive alteration for SCD.

Impact of metabolic syndrome on postoperative outcomes of transsphenoidal pituitary surgery: analysis of U.S. nationwide inpatient sample data 2005-2018.

Introduction: Transsphenoidal surgery (TSS) is the preferred surgical method for most pituitary adenomas owing to high efficacy and low mortality. This study aimed to evaluate the influence of metabolic syndrome (MetS) on postoperative outcomes of TSS for pituitary adenoma. Methods: This population-based, retrospective observational study extracted data of adults 20-79 y receiving TSS for pituitary adenoma from the US Nationwide Inpatient Sample (NIS) between 2005-2018. Primary outcomes were pituitary-related complications, poor outcomes (i.e., in-hospital mortality or unfavorable discharge), prolonged length of stay (LOS), and patient safety indicators (PSIs). Univariate and multivariate regressions were performed to determine the associations between study variables and outcomes. Results: 19,076 patients (representing a 93,185 US in-patient population) were included, among which 2,109 (11.1%) patients had MetS. After adjustment, pre-existing MetS was not significantly associated with presence of pituitary-related complications and poor outcomes. In contrast, MetS was significantly associated with an increased risk for prolonged LOS (adjusted OR (aOR) = 1.19; 95% CI: 1.05-1.34), PSIs (aOR = 1.31; 95% CI: 1.07-1.59) and greater hospital costs (adjusted ß = 8.63 thousand USD; 95% CI: 4.98-12.29). Among pituitary-related complications, MetS was independently associated with increased risk of cerebrospinal fluid (CSF) rhinorrhea (aOR = 1.22, 95% CI: 1.01, 1.47) but lowered diabetes insipidus (aOR = 0.83, 95% CI: 0.71, 0.97). Discussion: MetS does not pose excessive risk of in-hospital mortality or unfavorable discharge. However, MetS independently predicted having PSIs, prolonged LOS, greater hospital costs, and CSF rhinorrhea. Study findings may help clinicians achieve better risk stratification before TSS.

Psychometric properties and factor structure of the traditional Chinese version of the Community Integration Questionnaire-Revised in traumatic brain injury survivors.

This study aimed to translate and validate the traditional Chinese version of the Community Integration Questionnaire-Revised (TC-CIQ-R) in patients with traumatic brain injury (TBI). We included participants aged ≥20 years and diagnosed as having TBI for ≥6 months from neurosurgical clinics. The 18-item TC-CIQ-R, Participation Measure - 3 Domains, 4 Dimensions (PM-3D4D), Extended Glasgow Outcome Scale (GOSE), and Taiwanese Quality of Life After Brain Injury (TQOLIBRI) were completed. The sample included 180 TBI survivors (54% male, mean age 47 years) of whom 87% sustained a mild TBI. Exploratory factor analysis extracted four factors - home integration, social integration, productivity, and electronic social networking - which explained 63.03% of the variation, after discarding the tenth item with a factor loading of 0.25. For criterion-related validity, the TC-CIQ-R was significantly correlated with the PM-3D4D; convergent validity was exhibited by demonstrating the associations between the TC-CIQ-R and TQOLIBRI. Known-group validity testing revealed significant differences in the subdomain and total scores of the TC-CIQ-R between participants with a mean GOSE score of ≤6 and >7 (all P  < 0.001). The TC-CIQ-R exhibited acceptable Cronbach's α values (0.68-0.88). We suggest the 17-item TC-CIQ-R as a valid tool for rehabilitation professionals, useful for both clinical practice and research in assessing community integration levels following TBI.

Life After Traumatic Brain Injury: Effects on the Lifestyle and Quality of Life of Community-Dwelling Patients.

Persons who have experienced traumatic brain injury (TBI) may encounter a range of changes in their physical, mental, and cognitive functions as well as high fatigue levels. To gain a comprehensive understanding of the challenges faced by persons after TBI, we conducted multi-domain assessments among community-dwelling persons with a history of TBI and compared them with age- and sex-matched controls from the Northeastern Taiwan Community Medicine Research Cohort between 2019 and 2021. A total of 168 persons with TBI and 672 non-TBI controls were not different in terms of demographics, comorbidities, and physiological features. However, compared with the non-TBI group, the TBI group had a distinct lifestyle that involved increased reliance on analgesics (6.9% vs. 15.0%, respectively; p = 0.001) and sleep aids (p = 0.008), which negatively affected their quality of life. Moreover, they consumed more coffee (p < 0.001), tea (p < 0.001), cigarettes (p = 0.002), and betel nuts (p = 0.032) than did the non-TBI group. Notably, the use of coffee had a positive effect on the quality of life of the TBI group (F = 4.034; p = 0.045). Further, compared with the non-TBI group, the TBI group had increased risks of sarcopenia (p = 0.003), malnutrition (p = 0.003), and anxiety (p = 0.029) and reduced blood levels of vitamin D (29.83 ± 10.39 vs. 24.20 ± 6.59 ng/mL, respectively; p < 0.001). Overall, the TBI group had a reduced health-related quality of life, with significant challenges related to physical health, mental well-being, social interactions, pain management, and fatigue levels. Moreover, the TBI group experienced poorer sleep quality and efficiency than did the non-TBI group. In conclusion, persons who have sustained brain injuries that require comprehensive and holistic care that includes lifestyle modification, mental and physical healthcare plans, and increased long-term support from their communities. ClinicalTrials.gov (identifier: NCT04839796).

Psoriatic arthritis increases the risk of venous thromboembolism following degenerative lumbar spine surgery: An analysis of U.S. Nationwide Inpatient Sample 2005-2018.

Background: This retrospective study aimed to determine the risk of venous thromboembolism (VTE) in patients with PsA after surgery for lumbar degenerative disease (LDD). Methods: The study data of adults aged ≥20 years admitted to U.S. hospitals with diagnoses of LDD and undergoing spinal decompression or fusion between 2005 and 2018 were extracted from the National Inpatient Sample (NIS) database. Patients were further divided into two groups based on a diagnosis of PsA or not via codes ICD-9: 696.0 and ICD-10: L40.50. Patients with missing information were excluded. Propensity score matching (PSM) was employed to enhance comparability between groups. Logistic regression was used to determine associations between PsA and various outcomes, including complications, unfavorable discharge, and prolonged length of stay (LOS). Results: Data on 471,283 patients with LDD was extracted from the NIS database.from 2005 to 2018. Before propensity score matching, patients with PsA had higher proportions of overall morbidity (8.8 % vs. 6.9 %), VTE (1.4 % vs. 0.7 %), and unfavorable discharge (20.8 % vs. 16.9 %). After matching, patients with PsA still had higher VTE incidence and unfavorable discharge proportions. After adjustments, multivariable regression analysis indicated that patients with PsA had a higher risk of unfavorable discharge (aOR: 1.26, 95 % CI: 1.03-1.55) and VTE (aOR: 1.99, 95 % CI: 1.05-3.75). Conclusions: Among patients undergoing surgery for LDD, pre-existing PsA may be associated with increased risks of unfavorable discharge and VTE occurrence. The findings may benefit preoperative risk stratifications before LDD surgeries.

Psychometric properties and structural validity of traditional Chinese version of the Richards-Campbell Sleep Questionnaire in intensive care unit patients without physical restraint.

BACKGROUND: Sleep assessment in the intensive care unit (ICU) is difficult and often unreliable. The most commonly used questionnaire for assessing ICU sleep, the Richards-Campbell Sleep Scale (RCSQ), has not been tested for reliability and construct validity in the Mandarin-Taiwanese speaking population. OBJECTIVE: The objective of this study was to test the construct validity and criterion validity of the traditional Chinese version of RCSQ (TC-RCSQ) in critically ill patients without physical restraint. METHODS: We adopted a cross-sectional study design. Adults aged 20 years and above were recruited from a plastic surgery ICU of a medical center. The Cronbach's alpha was used to test internal consistency; the validity testing included content validity, criterion validity, and construct validity. Criterion validity was analysed by testing the association of TC-RCSQ with the Chinese version of Verran and Snyder-Halpern Sleep Questionnaire and sleep parameter of actigraphy using the Pearson correlation coefficient; construct validity was analysed using exploratory factor analysis. RESULTS: A total of 100 patients were included with a mean age of 49.78 years. Internal consistency reliability suggested Cronbach's alpha of 0.93. Moderate to strong correlations of TC-RCSQ with Verran-Snyder-Halpern Sleep Questionnaire were identified (r = 0.36 to 0.80, P < 0.05). We found significant correlations of actigraphic sleep efficiency with difficulty of falling sleep, awakening times, sleep quality, and total score of the TC-RCSQ (r = 0.23, 0.23, 0.20, and 0.23, P < 0.05). One factor (named as overall sleep quality) was extracted by exploratory factor analysis with a total variance explained of 78.40 %, which had good construction validity. CONCLUSIONS: The TC-RCSQ yields satisfactory reliability and validity in critically ill patients. Actigraphic sleep efficiency may be a single index for objectively sleep assessment of sleep quality in patients without physical restraint. Both the TC-RCSQ and actigraphy can aid nurses to evaluate the sleep quality in critically ill patients without physical restraint.

Predictors for delayed awakening in adult glioma patients receiving awake craniotomy under monitored anesthesia care.

PURPOSE: Delayed awakening after anesthetic discontinuation during awake craniotomy is associated with somnolence during functional brain mapping. However, predictors of delayed awakening in patients receiving monitored anesthesia care for awake craniotomy are unknown. METHODS: This retrospective cohort study analyzed 117 adult patients with supratentorial glioma in or near eloquent areas who received monitored anesthesia care for awake craniotomy between July 2020 and January 2023 at Linkou Chang Gung Memorial Hospital. These patients were divided into two groups according to their time to awakening (ability to speak their names) after propofol cessation: longer or shorter than 20 min (median duration). Because propofol was solely used anesthetic from skin incision to dural opening, parameters in Schnider model for propofol target-controlled infusion, such as age, sex, and BMI, were adjusted or propensity-matched to compare their anesthetic, surgical, and histopathological profiles. RESULTS: After propensity-matched comparisons of age and BMI, significant predictors of delayed awakening included IDH1 wild-type tumors and repeated craniotomies. Subgroup analysis revealed that older age and larger T2 volume were predictors in patients undergoing the first craniotomy, while lower preoperative Karnofsky performance scale scores and depression were predictors in repeated craniotomy cases. Delayed awakening was also associated with somnolence and a lower gross total resection rate. CONCLUSION: Our retrospective analysis of patients receiving monitored anesthesia care for awake craniotomy revealed that delayed awakening after propofol discontinuation occurred more often in patients with IDH1 wild-type tumors and repeated craniotomies. Also, delayed awakening was associated with somnolence during functional mapping and a lower gross total resection rate.

Dynamic Prevalence of and Factors Associated With Fatigue Following Traumatic Brain Injury: A Systematic Review and Meta-analysis of Observational Studies.

OBJECTIVE: To implement a systematic review and meta-analysis to comprehensively synthesize the prevalence of and factors associated with fatigue following traumatic brain injury (TBI). METHODS: We systematically searched the PubMed, EMBASE, Cochrane Library, Cumulated Index to Nursing and Allied Health Literature, PsycINFO, and ProQuest Dissertations and Theses A&I databases in all fields from their inception to March 31, 2021. We included observational studies investigating fatigue at specific time points following TBI or factors associated with post-TBI fatigue. All data were analyzed using a random-effects model. RESULTS: This meta-analysis included 29 studies that involved 12 662 patients with TBI and estimated the prevalence of post-TBI fatigue (mean age = 41.09 years); the meta-analysis also included 23 studies that involved 6681 patients (mean age = 39.95 years) and investigated factors associated with post-TBI fatigue. In patients with mild-to-severe TBI, the fatigue prevalence rates at 2 weeks or less, 1 to 3 months, 6 months, 1 year, and 2 years or more after TBI were 52.2%, 34.6%, 36.0%, 36.1%, and 48.8%, respectively. Depression (r = 0.48), anxiety (r = 0.49), sleep disturbance (r = 0.57), and pain (r = 0.46) were significantly associated with post-TBI fatigue. No publication bias was identified among the studies, except for those assessing fatigue prevalence at 6 months after TBI. CONCLUSION: The pooled prevalence rates of post-TBI fatigue exhibited a U-shaped pattern, with the lowest prevalence rates occurring at 1 to 3 months after TBI. Depression, anxiety, sleep disturbance, and pain were associated with post-TBI fatigue. Younger patients and male patients were more likely to experience post-TBI fatigue. Our findings can assist healthcare providers with identifying appropriate and effective interventions targeting post-TBI fatigue at specific periods.

Neuropsychological impairment in primary malignant brain tumor patients with awake craniotomy: a hospital-based registration study.

PURPOSE: Neuroplasticity is an ability to maintain neural circuit function when facing damages. It is one of the reasons that making brain tumors notorious. Therefore, we evaluated the characteristics of patients with primary brain tumors, compared neuropsychological deficits between patients who had awake craniotomy with left- or right-sided tumors, and analyzed the association between white matter tracts and neuropsychological deficits in patients with right-sided tumors. METHODS: Using the registration dataset of Chang Gung Memory Hospital between 2014 and 2020, this study included a total of 698 adult patients who received craniotomy for primary brain tumors (538 of conventional craniotomy; 160 of awake craniotomy). Neuropsychological assessments were arranged in patients as preoperative evaluation for awake craniotomies. RESULTS: A lower proportion of right-sided tumors was noted in patient who had awake craniotomy than those who had conventional craniotomy (33.8% and 51.5%, p < 0.001). In awake craniotomy, 88.7% of patients with left-sided tumors and 77.8% of patients with right-sided tumors had neuropsychological impairment. Patients with left-sided tumors had worse preoperative performance compared to those with right-sided tumors in global function (36.2% and 8.0%, p < 0.001), language domain (57.6% and 22.2%, p < 0.001), and attention (36.0% and 18.5%, p = 0.02). Furthermore, in those with right-sided low-grade gliomas, patients involving pathway of superior longitudinal fasciculus (SLF) I had a higher risk of deficits than those without involvement in verbal memory (p = 0.001, Odd ratio = 11.2, 95% CI = 1.8 ~ 71.4) and visual memory (p = 0.048, Odd ratio = 10.5, 95% CI = 1.0 ~ 111). CONCLUSION: In awake craniotomy, patients with left-sided brain tumors had worse cognitive function than those with right-sided tumors in terms of global function, language, and attention. 77% of patients with right-sided tumors had neuropsychological impairment. Therefore, a comprehensive neuropsychological evaluation and awake craniotomy are necessary for patients with brain tumors.

Outcomes of hemorrhagic stroke in patients with autoimmune rheumatic diseases: An analysis of the US Nationwide Inpatient Sample.

AIM: To determine whether and how rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) affect outcomes in patients admitted for hemorrhagic stroke. METHODS: This study screened the Nationwide Inpatient Sample database for adults aged ≥20 years admitted to US hospitals with a principal diagnosis of intracerebral hemorrhage (ICH) between 2005 and 2018. Diagnoses were determined using the International Classification of Diseases, 9th and 10th revisions (ICD-9 and ICD-10) diagnostic codes for ICH (ICD-9: 431, 432; ICD-10: I61, I62). Study outcomes were: (1) in-hospital mortality; (2) unfavorable discharge, defined as transfer to nursing homes or long-term care facilities; and (3) prolonged length of stay (LOS), defined as LOS >75th centile. RESULTS: Associations between comorbid RA, SLE, and SSc and clinical outcomes show a significantly lower risk of in-hospital mortality and prolonged LOS in RA patients. After admissions for ICH, the risk for in-hospital mortality and prolonged LOS was decreased in RA patients, and the risk for unfavorable discharge (long-term care) was reduced in SLE patients. CONCLUSIONS: Among patients admitted to US hospitals for hemorrhagic stroke, patients with RA had decreased risk for in-hospital mortality and prolonged LOS.

Delirium assessment tools among hospitalized older adults: A systematic review and metaanalysis of diagnostic accuracy.

Delirium is a common neuropsychiatric syndrome that is often overlooked in clinical settings. The most accurate instrument for screening delirium has not been established. This study aimed to compare the diagnostic accuracy of the 4 'A's Test (4AT), Nursing Delirium Screening Scale (Nu-DESC), and Confusion Assessment Method (CAM) in detecting delirium among older adults in clinical settings. These assessment tools feature concise item sets and straightforward administration procedures. Five electronic databases were systematically searched from their inception to September 7, 2022. Studies evaluating the sensitivity and specificity of the 4AT, Nu-DESC, and CAM against the Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases as the reference standard were included. Bivariate random effects model was used to summarize the sensitivity and specificity results. A total of 38 studies involving 7378 patients were included. The 4AT, Nu-DESC, and CAM had comparable sensitivity in detecting delirium (0.76, 0.78, and 0.80, respectively). However, the specificity of the CAM was higher than that of the 4AT (0.98 vs 0.89, P = .01) and Nu-DESC 0.99 vs 0.90, P = .003). Diagnostic accuracy was moderated by the percentage of women, acute care setting, sample size, and assessors. The three tools exhibit comparable sensitivity, and the CAM has the highest specificity. Based on the feasibility of the tools, nurses and clinical staffs could employ the Nu-DESC and the 4AT on screening out positive delirium cases and integrate these tools into daily practice. Further investigations are warranted to verify our findings.

Microsystem Advances through Integration with Artificial Intelligence.

Microfluidics is a rapidly growing discipline that involves studying and manipulating fluids at reduced length scale and volume, typically on the scale of micro- or nanoliters. Under the reduced length scale and larger surface-to-volume ratio, advantages of low reagent consumption, faster reaction kinetics, and more compact systems are evident in microfluidics. However, miniaturization of microfluidic chips and systems introduces challenges of stricter tolerances in designing and controlling them for interdisciplinary applications. Recent advances in artificial intelligence (AI) have brought innovation to microfluidics from design, simulation, automation, and optimization to bioanalysis and data analytics. In microfluidics, the Navier-Stokes equations, which are partial differential equations describing viscous fluid motion that in complete form are known to not have a general analytical solution, can be simplified and have fair performance through numerical approximation due to low inertia and laminar flow. Approximation using neural networks trained by rules of physical knowledge introduces a new possibility to predict the physicochemical nature. The combination of microfluidics and automation can produce large amounts of data, where features and patterns that are difficult to discern by a human can be extracted by machine learning. Therefore, integration with AI introduces the potential to revolutionize the microfluidic workflow by enabling the precision control and automation of data analysis. Deployment of smart microfluidics may be tremendously beneficial in various applications in the future, including high-throughput drug discovery, rapid point-of-care-testing (POCT), and personalized medicine. In this review, we summarize key microfluidic advances integrated with AI and discuss the outlook and possibilities of combining AI and microfluidics.

Acrolein produced by glioma cells under hypoxia inhibits neutrophil AKT activity and suppresses anti-tumoral activities.

Acrolein, which is the most reactive aldehyde, is a byproduct of lipid peroxidation in a hypoxic environment. Acrolein has been shown to form acrolein-cysteine bonds, resulting in functional changes in proteins and immune effector cell suppression. Neutrophils are the most abundant immune effector cells in circulation in humans. In the tumor microenvironment, proinflammatory tumor-associated neutrophils (TANs), which are termed N1 neutrophils, exert antitumor effects via the secretion of cytokines, while anti-inflammatory neutrophils (N2 neutrophils) support tumor growth. Glioma is characterized by significant tissue hypoxia, immune cell infiltration, and a highly immunosuppressive microenvironment. In glioma, neutrophils exert antitumor effects early in tumor development but gradually shift to a tumor-supporting role as the tumor develops. However, the mechanism of this anti-to protumoral switch in TANs remains unclear. In this study, we found that the production of acrolein in glioma cells under hypoxic conditions inhibited neutrophil activation and induced an anti-inflammatory phenotype by directly reacting with Cys310 of AKT and inhibiting AKT activity. A higher percentage of cells expressing acrolein adducts in tumor tissue are associated with poorer prognosis in glioblastoma patients. Furthermore, high-grade glioma patients have increased serum acrolein levels and impaired neutrophil functions. These results suggest that acrolein suppresses neutrophil function and contributes to the switch in the neutrophil phenotype in glioma.

Vascular risk factors and astrocytic marker for the glymphatic system activity.

OBJECTIVES: Glymphatic system maintains brain fluid circulation via active transportation of astrocytic aquaporin-4 in perivascular space. The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) is an established method measuring perivascular glymphatic activity, but comprehensive investigations into its influential factors are lacking. METHODS: Community-dwelling older adults underwent brain MRI scans, neuropsychiatric, and multi-domain assessments. Blood biomarker tests included glial fibrillary acidic protein (GFAP) for astrocyte injury. RESULTS: In 71 enrolled participants, the DTI-ALPS index was associated with modifiable factors, including lipid profile (high-density lipoprotein, r = 0.396; very-low-density lipoprotein, r = - 0.342), glucose intolerance (diabetes mellitus, standardized mean difference (SMD) = 0.7662; glycated hemoglobin, r = - 0.324), obesity (body mass index, r = - 0.295; waist, r = - 0.455), metabolic syndrome (SMD = - 0.6068), cigarette-smoking (SMD = - 0.6292), and renal clearance (creatinine, r = - 0.387; blood urea nitrogen, r = - 0.303). Unmodifiable associative factors of DTI-ALPS were age (r = - 0.434) and sex (SMD = 1.0769) (all p < 0.05). A correlation of DTI-ALPS and blood GFAP was noticed (r = - 0.201, one-tailed t-test for the assumption that astrocytic injury impaired glymphatic activity, p = 0.046). Their cognitive correlations diverged, domain-specific for DTI-ALPS (Facial Memory Test, r = 0.272, p = 0.022) but global cognition-related for blood GFAP (MoCA, r = - 0.264, p = 0.026; ADAS-cog, r = 0.304, p = 0.010). CONCLUSION: This correlation analysis revealed multiple modifiable and unmodifiable association factors to the glymphatic image marker. The DTI-ALPS index correlated with various metabolic factors that are known to increase the risk of vascular diseases such as atherosclerosis. Furthermore, the DTI-ALPS index was associated with renal indices, and this connection might be a link of water regulation between the two systems. In addition, the astrocytic biomarker, plasma GFAP, might be a potential marker of the glymphatic system; however, more research is needed to confirm its effectiveness.

Effects of Neurofeedback on Cognitive Function, Productive Activity, and Quality of Life in Patients With Traumatic Brain Injury: A Randomized Controlled Trial.

BACKGROUND: Cognitive impairment is common in patients with traumatic brain injury (TBI). Studies that have examined the effectiveness of neurofeedback (NFB) on cognitive function following TBI have had poor study designs and small sample sizes. OBJECTIVES: This randomized controlled trial assessed the effects of low-resolution tomography Z-score NFB (LZNFB) and theta/beta NFB on cognitive impairment, return to productive activity, and quality of life in patients with TBI. METHODS: We randomly assigned 87 patients with TBI with cognitive impairment to LZNFB, theta/beta NFB, or usual care (UC) groups. Patients in both NFB groups received weekly 60-minute treatment for 10 weeks, and those in the control group received UC and telephone interviews for 10 weeks. The primary outcome was cognitive function as measured by performance on cognitive tasks; the secondary outcomes included productive activity and quality of life based on the Community Integration Questionnaire-revised (CIQ-R) and the Quality of Life after Brain Injury (QOLIBRI), respectively, at baseline and immediately after the last intervention. RESULTS: The LZNFB group exhibited significantly greater improvements in immediate recall, delayed recall, recognition memory, and selective attention compared with the UC group; the theta/beta NFB group exhibited improvements in only immediate memory and selective attention (P < .05). The total CIQ-R scores of the LZNFB group after treatment were significantly improved than those of the UC group were. CONCLUSION: Consecutive LZNFB achieved therapeutic effects in memory, attention, and productive activity, whereas theta/beta NFB improved memory and attention in patients with TBI.This trial was prospectively registered at ClinicalTrial.gov (registration number: NCT03515317; https://clinicaltrials.gov/ct2/show/NCT03515317).

Augmented Reality Surgical Navigation System Integrated with Deep Learning.

Most current surgical navigation methods rely on optical navigators with images displayed on an external screen. However, minimizing distractions during surgery is critical and the spatial information displayed in this arrangement is non-intuitive. Previous studies have proposed combining optical navigation systems with augmented reality (AR) to provide surgeons with intuitive imaging during surgery, through the use of planar and three-dimensional imagery. However, these studies have mainly focused on visual aids and have paid relatively little attention to real surgical guidance aids. Moreover, the use of augmented reality reduces system stability and accuracy, and optical navigation systems are costly. Therefore, this paper proposed an augmented reality surgical navigation system based on image positioning that achieves the desired system advantages with low cost, high stability, and high accuracy. This system also provides intuitive guidance for the surgical target point, entry point, and trajectory. Once the surgeon uses the navigation stick to indicate the position of the surgical entry point, the connection between the surgical target and the surgical entry point is immediately displayed on the AR device (tablet or HoloLens glasses), and a dynamic auxiliary line is shown to assist with incision angle and depth. Clinical trials were conducted for EVD (extra-ventricular drainage) surgery, and surgeons confirmed the system's overall benefit. A "virtual object automatic scanning" method is proposed to achieve a high accuracy of 1 ± 0.1 mm for the AR-based system. Furthermore, a deep learning-based U-Net segmentation network is incorporated to enable automatic identification of the hydrocephalus location by the system. The system achieves improved recognition accuracy, sensitivity, and specificity of 99.93%, 93.85%, and 95.73%, respectively, representing a significant improvement from previous studies.