Memantine alleviates cognitive impairment and hippocampal morphology injury in a mouse model of chronic alcohol exposure.

Alcohol-related cognitive impairment (ARCI) is highly prevalent among patients with alcohol abuse and dependence. The pathophysiology of ARCI, pivotal for refined therapeutic approaches, is not fully elucidated, posing a risk of progression to severe neurological sequelae such as Korsakoff's syndrome (KS) and Alcohol-Related Dementia (ARD). This study ventures into the underlying mechanisms of chronic alcohol-induced neurotoxicity, notably glutamate excitotoxicity and cytoskeletal disruption, and explores the therapeutic potential of Memantine, a non-competitive antagonist of the N-methyl-d-aspartate (NMDA) receptor known for its neuroprotective effect against excitotoxicity. Our investigation centers on the efficacy of Memantine in mitigating chronic alcohol-induced cognitive and hippocampal damages in vivo. Male C57BL/6J mice were subjected to 30 % (v/v, 6.0 g/kg) ethanol via intragastric administration alongside Memantine co-treatment (10 mg/kg/day, intraperitoneally) for six weeks. The assessment involved Y maze, Morris water maze, and novel object recognition tests to evaluate spatial and recognition memory deficits. Histopathological evaluations of the hippocampus were conducted to examine the extent of alcohol-induced morphological changes and the potential protective effect of Memantine. The findings reveal that Memantine significantly improves chronic alcohol-compromised cognitive functions and mitigates hippocampal pathological changes, implicating a moderating effect on the disassembly of actin cytoskeleton and microtubules in the hippocampus, induced by chronic alcohol exposure. Our results underscore Memantine's capability to attenuate chronic alcohol-induced cognitive and hippocampal morphological harm may partly through regulating cytoskeleton dynamics, offering valuable insights into innovative therapeutic strategies for ARCI.

Implementation of Sound Direction Detection and Mixed Source Separation in Embedded Systems.

In recent years, embedded system technologies and products for sensor networks and wearable devices used for monitoring people's activities and health have become the focus of the global IT industry. In order to enhance the speech recognition capabilities of wearable devices, this article discusses the implementation of audio positioning and enhancement in embedded systems using embedded algorithms for direction detection and mixed source separation. The two algorithms are implemented using different embedded systems: direction detection developed using TI TMS320C6713 DSK and mixed source separation developed using Raspberry Pi 2. For mixed source separation, in the first experiment, the average signal-to-interference ratio (SIR) at 1 m and 2 m distances was 16.72 and 15.76, respectively. In the second experiment, when evaluated using speech recognition, the algorithm improved speech recognition accuracy to 95%.

Central nervous system efficacy of aumolertinib versus gefitinib in patients with untreated, EGFR-mutated, advanced non-small cell lung cancer: data from a randomized phase III trial (AENEAS).

BACKGROUND: The initial randomized, double-blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study. METHODS: Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological-BICR). The primary endpoint for this subgroup analysis was CNS progression-free survival (PFS). RESULTS: Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological-BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17-0.56; P < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11-0.57; P < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed. CONCLUSIONS: These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR-mutated advanced NSCLC with baseline CNS metastases. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03849768.

[Spatial and Temporal Scale Effects of Landscape Pattern on Riverine Nitrogen and Phosphorus Nutrients in the Qingshan Lake Watershed].

The influences of landscape pattern on water quality are dependent on spatial-temporal scales. However, the effects of landscape composition, landscape configuration, and landscape slope metrics on seasonal water quality at different spatial scales remain unclear. Based on the total nitrogen, total phosphorus, nitrate-N, and ammonium-N data from 26 sampling sites in the Qingshan Lake watershed, this study coupled landscape pattern analysis, redundancy analysis, and partial redundancy analysis to quantify the spatiotemporal scale effects of landscape pattern on riverine nitrogen （N） and phosphorus （P） concentrations. The results showed that： ① The explanatory ability of landscape pattern at the sub-watershed scale on riverine N and P concentrations was 6.8%-8.4% higher than that at the buffer scale, and this effect was more obvious in the dry season. ② At the sub-watershed scale, the percentage of forestland and the interspersion and juxtaposition degree of residential land had a greater influence on riverine N and P concentrations. At the buffer scale, the slope of farmland and residential land and the aggregation degree of forestland patches were the key factors affecting riverine N and P concentrations. ③ The contribution rate of landscape configuration to riverine N and P concentration variations （20.1%-36.5%） was the highest. The sensitivity of the effect of landscape configuration on riverine N and P concentrations to seasonal changes was the highest, and the effect of landscape slope on riverine N and P concentrations had the highest sensitivity to spatial scale changes. Therefore, landscape pattern-regulated non-point source pollution should be considered from a multi-scale perspective. These results can provide scientific basis for the formulation of landscape pattern optimization measures aiming at non-point source pollution control.

The effect of low-level laser therapy on osteoclast differentiation: Clinical implications for tooth movement and bone density.

Background/purpose: Osteoclast differentiation is crucial for orchestrating both tooth movement and the maintenance of bone density. Therefore, the current study sought to explore the impact of low-level laser therapy (LLLT) on osteoclast differentiation, functional gene expression, molecular signaling pathways, and orthodontic tooth movement in clinical settings. Materials and methods: The RAW 264.7 cell line served as the precursor for osteoclasts, and these cells underwent irradiation using a 808-nm LLLT. Osteoclast differentiation was assessed through tartrate-resistant acid phosphatase (TRAP) staining. Functional gene expression levels were evaluated using real-time quantitative polymerase chain reaction (RT-qPCR) while signaling molecules were examined through Western blot analysis. In the clinical study, 12 participants were enrolled. Their tooth movement was monitored using a TRIOS desktop scanner. Bone density measurements were conducted using Mimics software, which processed cone-beam computed tomography (CBCT) images exported in Digital Imaging and Communications in Medicine (DICOM) format. Results: We found that LLLT effectively promoted receptor activator of nuclear factor-κB ligand (RANKL)-dependent osteoclast differentiation and the expression of osteoclast functional genes, including matrix metallopeptidase 9 (MMP9), nuclear factor of activated T-cells cytoplasmic 1(NFATc1), tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CTSK) in RAW264.7 cells. Clinically, the cumulative tooth movement over 90 days was significantly higher in the laser group than in the control group. Conclusion: Our research demonstrates that LLLT not only significantly promotes osteoclast differentiation but is also a valuable adjunct in orthodontic therapy.

Clinical efficacy of Gamma Knife® combined with transarterial chemoembolization and immunotherapy in the treatment of primary liver cancer.

BACKGROUND: This study was designed to investigate the clinical efficacy and safety of Gamma Knife® combined with transarterial chemoembolization (TACE) and immunotherapy in the treatment of primary liver cancer. AIM: To investigate the clinical efficacy and safety of Gamma Knife® combined with TACE and immune-targeted therapy in the treatment of primary liver cancer. METHODS: Clinical data from 51 patients with primary liver cancer admitted to our hospital between May 2018 and October 2022 were retrospectively collected. All patients underwent Gamma Knife® treatment combined with TACE and immunotherapy. The clinical efficacy, changes in liver function, overall survival (OS), and progression-free survival (PFS) of patients with different treatment responses were evaluated, and adverse reactions were recorded. RESULTS: The last follow-up for this study was conducted on October 31, 2023. Clinical evaluation of the 51 patients with primary liver cancer revealed a partial response (PR) in 27 patients, accounting for 52.94% (27/51); stable disease (SD) in 16 patients, accounting for 31.37% (16/51); and progressive disease (PD) in 8 patients, accounting for 15.69% (8/51). The objective response rate was 52.94%, and the disease control rate was 84.31%. Alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alpha-fetoprotein isoform levels decreased after treatment compared with pretreatment (all P = 0.000). The median OS was 26 months [95% confidence interval (95%CI): 19.946-32.054] in the PR group and 19 months (95%CI: 14.156-23.125) in the SD + PD group, with a statistically significant difference (P = 0.015). The median PFS was 20 months (95%CI: 18.441-34.559) in the PR group and 12 months (95%CI: 8.745-13.425) in the SD + PD group, with a statistically significant difference (P = 0.002). Common adverse reactions during treatment included nausea and vomiting (39.22%), thrombocytopenia (27.45%), and leukopenia (25.49%), with no treatment-related deaths reported. CONCLUSION: Gamma Knife® combined with TACE and immune-targeted therapy is safe and effective in the treatment of primary liver cancer and has a good effect on improving the clinical benefit rate and liver function of patients.

Escitalopram moderately outperforms citalopram towards anti-neuroinflammation and neuroprotection in 6-hydroxydopamine-induced mouse model of Parkinson's disease.

Citalopram and escitalopram are structurally close-related antidepressants and both forms are widely used in the world. We aimed to comparatively evaluate the anti-neuroinflammatory and neuroprotective effects of escitalopram and citalopram in Parkinson's disease (PD) mouse model. Mice were randomly divided into six groups and received 6-hydroxydopamine (6-OHDA) or vehicle administration. The mice were then treated with escitalopram, citalopram or saline for consecutive 7 days. Behaviors, neuroinflammation, neurotransmitters, and neurotoxicity were assessed. Results showed that citalopram but not escitalopram worsened body weight loss and increased freezing time in the PD mice. Both drugs had no impact on the anxiety-like behaviors but ameliorated the depressive-like behaviors as in elevated plus maze and sucrose splash tests. Escitalopram but not citalopram ameliorated motor discoordination in the PD mice as in rotarod test. In accordance, escitalopram but not citalopram attenuated the 6-OHDA-induced nigrostriatal dopaminergic loss. Further mechanistic investigations showed that both drugs mitigated activations of microglia and astrocytes and/or levels of pro-inflammatory cytokines in the PD mice, but escitalopram showed appreciably better effects in the substantia nigra. Neurotransmitter examination in the prefrontal cortex suggested that the two drugs had comparable effects on the disturbed neurotransmitters in the PD mice, but citalopram was prone to disrupt certain normal homeostasis. In conclusion, escitalopram is moderately superior than citalopram to suppress neuroinflammation and to protect against dopaminergic neuronal death and motor discoordination in the 6-OHDA-induced PD mice. Our findings imply that escitalopram shall be prescribed with priority over citalopram to treat PD patients with depression as escitalopram may meanwhile provide greater additional benefits to the patients.

SHR-A1811 (antibody-drug conjugate) in advanced HER2-mutant non-small cell lung cancer: a multicenter, open-label, phase 1/2 study.

A dose-escalation and expansion, phase 1/2 study (ClinicalTrials.gov, NCT04818333) was conducted to assess the novel antibody-drug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer (NSCLC). Here, we report results from the phase 1 portion. Patients who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 weeks. Dose escalation followed a Bayesian logistic regression model that included overdose control, with subsequent selection of tolerable levels for dose expansion. Overall, 63 patients were enrolled, including 43 receiving a recommended dose for expansion of 4.8 mg/kg. All patients had HER2-mutant disease. Dose-limiting toxicity occurred in one patient in the 8.0 mg/kg dose cohort. Grade ≥ 3 treatment-related adverse events occurred in 29 (46.0%) patients. One patient in the 6.4 mg/kg cohort died due to interstitial lung disease. As of April 11, 2023, the 4.8 mg/kg cohort showed an objective response rate of 41.9% (95% CI 27.0-57.9), and a disease control rate of 95.3% (95% CI 84.2-99.4). The median duration of response was 13.7 months, with 13 of 18 responses ongoing. The median progression-free survival was 8.4 months (95% CI 7.1-15.0). SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutant NSCLC.

The YY1-CPT1C signaling axis modulates the proliferation and metabolism of pancreatic tumor cells under hypoxia.

Carnitine palmitoyltransferase 1C (CPT1C) is an enzyme that regulates tumor cell proliferation and metabolism by modulating mitochondrial function and lipid metabolism. Hypoxia, commonly observed in solid tumors, promotes the proliferation and progression of pancreatic cancer by regulating the metabolic reprogramming of tumor cells. So far, the metabolic regulation of hypoxic tumor cells by CPT1C and the upstream mechanisms of CPT1C remain poorly understood. Yin Yang 1 (YY1) is a crucial oncogene for pancreatic tumorigenesis and acts as a transcription factor that is involved in multiple metabolic processes. This study aimed to elucidate the relationship between YY1 and CPT1C under hypoxic conditions and explore their roles in hypoxia-induced proliferation and metabolic alterations of tumor cells. The results showed enhancements in the proliferation and metabolism of PANC-1 cells under hypoxia, as evidenced by increased cell growth, cellular ATP levels, up-regulation of mitochondrial membrane potential, and decreased lipid content. Interestingly, knockdown of YY1 or CPT1C inhibited hypoxia-induced rapid cell proliferation and vigorous cell metabolism. Importantly, for the first time, we reported that YY1 directly activated the transcription of CPT1C and clarified that CPT1C was a novel target gene of YY1. Moreover, the YY1 and CPT1C were found to synergistically regulate the proliferation and metabolism of hypoxic cells through transfection with YY1 siRNA to CRISPR/Cas9-CPT1C knockout PANC-1 cells. Taken together, these results indicated that the YY1-CPT1C axis could be a new target for the intervention of pancreatic cancer proliferation and metabolism.

Oxidative Difunctionalization of N-Aryl Bicyclobutyl Amides with Aldehydes: Divergent Synthesis of Acylated and Alkylated 3-Spirocyclobutyl Oxindoles.

An efficient and operationally simple oxidative radical difunctionalization of N-aryl bicyclobutyl (BCB) amides with aldehydes is described. It was found that acylated 3-spirocyclobutyl oxindoles were generated from the coupling of BCB-amides and aromatic aldehydes, while reactions gave exclusively decarbonylative alkylarylation products using alkyl aldehydes as radical precursors.

Predictors of futile recanalization after endovascular treatment of acute ischemic stroke.

OBJECTIVE: Endovascular therapy (EVT) is the most successful treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation. However, futile recanalization (FR) seriously affects the prognosis of these patients. The aim of this study was to investigate predictors of FR after EVT in patients with AIS. METHOD: Patients diagnosed with AIS due to anterior circulation LVO and receiving EVT between June 2020 and October 2022 were prospectively enrolled. FR after EVT was defined as a poor 90-day prognosis (modified Rankin Scale [mRS] score ≥ 3) despite achieving successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] classification of 2b-3). All included patients were categorized into control group (mRS score < 3) and FR group (mRS score ≥ 3). Demographic characteristics, comorbidities (hypertension, diabetes, atrial fibrillation, smoking, etc.), stroke-specific data (NIHSS score, ASPECT score and site of occlusion), procedure data (treatment type [direct thrombectomy vs. bridging thrombectomy], degree of vascular recanalization [mTICI], procedure duration time and onset-recanalization time), laboratory indicators (lymphocytes count, neutrophils count, monocytes count, C-reactive protein, neutrophil-to-lymphocyte ratio [NLR], monocyte-to-high-density lipoprotein ratio [MHR], lymphocyte-to-monocyte ratio [LMR], lymphocyte-to-C-reactive protein ratio [LCR], lymphocyte-to-high-density lipoprotein ratio[LHR], total cholesterol and triglycerides.) were compared between the two groups. Multivariate logistic regression analysis was performed to explore independent predictors of FR after EVT. RESULTS: A total of 196 patients were included in this study, among which 57 patients were included in the control group and 139 patients were included in the FR group. Age, proportion of patients with hypertension and diabetes mellitus, median NIHSS score, CRP level, procedure duration time, neutrophil count and NLR were higher in the FR group than in the control group. Lymphocyte count, LMR, and LCR were lower in the FR group than in the control group. There were no significant differences in platelet count, monocytes count, total cholesterol, triglycerides, HDL, LDL, gender, smoking, atrial fibrillation, percentage of occluded sites, onset-recanalization time, ASPECT score and type of treatment between the two groups. Multivariate logistic regression analysis demonstrated that NLR was independently associated with FR after EVT (OR = 1.37, 95%CI = 1.005-1.86, P = 0.046). CONCLUSION: This study demonstrated that high NLR was associated with a risk of FR in patients with AIS due to anterior circulation LVO. These findings may help clinicians determine which patients with AIS are at higher risk of FR after EVT. Our study can provide a theoretical basis for interventions in the aforementioned population.

Morphological and Phylogenetic Analyses Reveal Three New Species of Entomopathogenic Fungi Belonging to Clavicipitaceae (Hypocreales, Ascomycota).

This study aims to report three new species of Conoideocrella and Moelleriella from Yunnan Province, Southwestern China. Species of Conoideocrella and Moelleriella parasitize scale insects (Coccidae and Lecaniidae, Hemiptera) and whiteflies (Aleyrodidae, Hemiptera). Based on the phylogenetic analyses of the three-gene nrLSU, tef-1α, and rpb1, it showed one new record species (Conoideocrella tenuis) and one new species (Conoideocrella fenshuilingensis sp. nov.) in the genus Conoideocrella, and two new species, i.e., Moelleriella longzhuensis sp. nov. and Moelleriella jinuoana sp. nov. in the genus Moelleriella. The three new species were each clustered into separate clades that distinguished themselves from one another. All of them were distinguishable from their allied species based on their morphology. Morphological descriptions, illustrations, and comparisons of the allied taxa of the four species are provided in the present paper. In addition, calculations of intraspecific and interspecific genetic distances were performed for Moelleriella and Conoideocrella.

Fluorescent chemosensors facilitate the visualization of plant health and their living environment in sustainable agriculture.

Globally, 91% of plant production encounters diverse environmental stresses that adversely affect their growth, leading to severe yield losses of 50-60%. In this case, monitoring the connection between the environment and plant health can balance population demands with environmental protection and resource distribution. Fluorescent chemosensors have shown great progress in monitoring the health and environment of plants due to their high sensitivity and biocompatibility. However, to date, no comprehensive analysis and systematic summary of fluorescent chemosensors used in monitoring the correlation between plant health and their environment have been reported. Thus, herein, we summarize the current fluorescent chemosensors ranging from their design strategies to applications in monitoring plant-environment interaction processes. First, we highlight the types of fluorescent chemosensors with design strategies to resolve the bottlenecks encountered in monitoring the health and living environment of plants. In addition, the applications of fluorescent small-molecule, nano and supramolecular chemosensors in the visualization of the health and living environment of plants are discussed. Finally, the major challenges and perspectives in this field are presented. This work will provide guidance for the design of efficient fluorescent chemosensors to monitor plant health, and then promote sustainable agricultural development.

Association analyses of apolipoprotein E genotypes and cognitive performance in patients with Parkinson's disease.

BACKGROUND: Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD). The apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer's disease (AD). However, the effect of APOEε4 on cognitive function of PD patients remains unclear. In this study, we aimed to understand whether and how carrying APOEε4 affects cognitive performance in patients with early-stage and advanced PD. METHODS: A total of 119 Chinese early-stage PD patients were recruited. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Hamilton anxiety scale, Hamilton depression scale, non-motor symptoms scale, Mini-mental State Examination, Montreal Cognitive Assessment, and Fazekas scale were evaluated. APOE genotypes were determined by polymerase chain reactions and direct sequencing. Demographic and clinical information of 521 early-stage and 262 advanced PD patients were obtained from Parkinson's Progression Marker Initiative (PPMI). RESULTS: No significant difference in cognitive performance was found between ApoEε4 carriers and non-carriers in early-stage PD patients from our cohort and PPMI. The cerebrospinal fluid (CSF) Amyloid Beta 42 (Aß42) level was significantly lower in ApoEε4 carrier than non-carriers in early-stage PD patients from PPMI. In advanced PD patients from PPMI, the BJLOT, HVLT retention and SDMT scores seem to be lower in ApoEε4 carriers without reach the statistical significance. CONCLUSIONS: APOEε4 carriage does not affect the cognitive performance of early-stage PD patients. However, it may promote the decline of CSF Aß42 level and the associated amyloidopathy, which is likely to further contribute to the cognitive dysfunction of PD patients in the advanced stage.

Photoredox Ring Opening 1,2-Alkylarylation of Alkenes with Sulfonium Salts Toward Thioether-Substituted Oxindoles.

A novel strategy for the difunctionalization of electron-deficient alkenes with aryl sulfonium salts to access remote sulfur-containing oxindole derivatives by using in situ-formed copper(I)-based complexes as a photoredox catalyst is presented. This method enables the generation of the C(sp3)-centered radicals through site selective cleavage of the C-S bond of aryl sulfonium salts under mild conditions. Moreover, the oxidation reactions of desired products provide a new strategy for the preparation of sulfoxide or sulfone-containing compounds. Importantly, this approach can be easily applied to late-stage modification of pharmaceuticals molecules.

Pregnane X receptor activation induces liver enlargement and regeneration and simultaneously promotes the metabolic activity of CYP3A1/2 and CYP2C6/11 in rats.

Human pregnane X receptor (PXR) is critical for regulating the expression of key drug-metabolizing enzymes such as CYP3A and CYP2C. Our recent study revealed that treatment with rodent-specific PXR agonist pregnenolone-16α-carbonitrile (PCN) significantly induced hepatomegaly and promoted liver regeneration after two-thirds partial hepatectomy (PHx) in mice. However, it remains unclear whether PXR activation induces hepatomegaly and liver regeneration and simultaneously promotes metabolic function of the liver. Here, we investigated the metabolism activity of CYP1A2, CYP3A1/2 and CYP2C6/11 during PXR activation-induced liver enlargement and regeneration in rats after cocktail dosing of CYP probe drugs. For PCN-induced hepatomegaly, a notable increase in the metabolic activity of CYP3A1/2 and CYP2C6/11, as evidenced by the plasma exposure of probe substrates and the AUC ratios of the characteristic metabolites to its corresponding probe substrates. The metabolic activity of CYP1A2, CYP3A1/2 and CYP2C6/11 decreased significantly after PHx. However, PCN treatment obviously enhanced the metabolic activity of CYP2C6/11 and CYP3A1/2 in PHx rats. Furthermore, the protein expression levels of CYP3A1/2 and CYP2C6/11 in liver were up-regulated. Taken together, this study demonstrates that PXR activation not only induces hepatomegaly and liver regeneration in rats, but also promotes the protein expression and metabolic activity of the PXR downstream metabolizing enzymes such as CYP3A1/2 and CYP2C6/11 in the body.

Developing a Cost-Effective Surgical Scheduling System Applying Lean Thinking and Toyota's Methods for Surgery-Related Big Data for Improved Data Use in Hospitals: User-Centered Design Approach.

BACKGROUND: Surgical scheduling is pivotal in managing daily surgical sequences, impacting patient experience and hospital resources significantly. With operating rooms costing approximately US $36 per minute, efficient scheduling is vital. However, global practices in surgical scheduling vary, largely due to challenges in predicting individual surgeon times for diverse patient conditions. Inspired by the Toyota Production System's efficiency in addressing similar logistical challenges, we applied its principles as detailed in the book "Lean Thinking" by Womack and Jones, which identifies processes that do not meet customer needs as wasteful. This insight is critical in health care, where waste can compromise patient safety and medical quality. OBJECTIVE: This study aims to use lean thinking and Toyota methods to develop a more efficient surgical scheduling system that better aligns with user needs without additional financial burdens. METHODS: We implemented the 5 principles of the Toyota system: specifying value, identifying the value stream, enabling flow, establishing pull, and pursuing perfection. Value was defined in terms of meeting the customer's needs, which in this context involved developing a responsive and efficient scheduling system. Our approach included 2 subsystems: one handling presurgery patient data and another for intraoperative and postoperative data. We identified inefficiencies in the presurgery data subsystem and responded by creating a comprehensive value stream map of the surgical process. We developed 2 Excel (Microsoft Corporation) macros using Visual Basic for Applications. The first calculated average surgery times from intra- or postoperative historic data, while the second estimated surgery durations and generated concise, visually engaging scheduling reports from presurgery data. We assessed the effectiveness of the new system by comparing task completion times and user satisfaction between the old and new systems. RESULTS: The implementation of the revised scheduling system significantly reduced the overall scheduling time from 301 seconds to 261 seconds (P=.02), with significant time reductions in the revised process from 99 seconds to 62 seconds (P<.001). Despite these improvements, approximately 21% of nurses preferred the older system for its familiarity. The new system protects patient data privacy and streamlines schedule dissemination through a secure LINE group (LY Corp), ensuring seamless flow. The design of the system allows for real-time updates and has been effectively monitoring surgical durations daily for over 3 years. The "pull" principle was demonstrated when an unplanned software issue prompted immediate, user-led troubleshooting, enhancing system reliability. Continuous improvement efforts are ongoing, except for the preoperative patient confirmation step, which requires further enhancement to ensure optimal patient safety. CONCLUSIONS: Lean principles and Toyota's methods, combined with computer programming, can revitalize surgical scheduling processes. They offer effective solutions for surgical scheduling challenges and enable the creation of a novel surgical scheduling system without incurring additional costs.

Attributional styles are associated with care burden in geriatric depression: older adults and their caregivers in Taiwan.

BACKGROUND: Given the rising prevalence of depression among older adults and the associated increase in caregiving responsibilities, understanding factors influencing caregiver burden is crucial. Previous research has not extensively explored the impact of caregivers' attributional styles, that is, how individuals interpret the causes of life events, on their care burden. AIM: This study examined the relationship between caregivers' attributional styles and their care burden for older patients with depression. METHODS: This cross-sectional study enrolled older adults aged ≥ 65 years diagnosed with depression and their caregivers. Depression was diagnosed according to the DSM-V criteria for Major Depressive Disorder or Persistent Depressive Disorder. Caregivers completed the Chinese Depression Caregiver Burden Scale (CDCBS) to assess care burden, the Hamilton Depression Rating Scale (HAM-D) to evaluate patient symptom severity, the Center for Epidemiological Studies Depression Scale (CES-D) for measuring caregivers' depression, and the Chinese Depression Patient Caregiver Attribution Style Scale (CDPCAS) to assess attributional styles. Hierarchical regression analysis was used to identify the factors independently associated with the caregiver's subjectively assessed care burden. RESULTS: The sample included 146 caregivers of geriatric patients with depression. Most depression patients were women (74.7%) with a mean age of 74.3 years, whereas the mean age of caregivers was 57.7 years. Hierarchical regression analysis identified that caregivers' gender (ß = - 0.14, p = .044), educational level (ß = 0.19, p = .008), caregivers' own depression assessed by the Center for Epidemiological Studies Depression Scale (ß = 0.41, p < .001), and attributional styles, particularly manipulation (ß = 0.29, p < .001) and illness/stress attributional style (ß = 0.23, p = .002) as independent factors associated with care burden. Patient symptom severity assessed using the Hamilton Depression Scale was not significantly correlated with care burden after controlling for attributional styles. CONCLUSIONS: Certain attributional styles, particularly the manipulation and illness/stress attributional styles, significantly increased self-reported care burden. These findings highlight the need for educational resources to change the attribution style, along with support systems and accessible mental health services for caregivers to potentially ease the care burden.

Prevalence of metabolic syndrome among patients with hepatocellular carcinoma of different etiologies: a retrospective study.

AIMS: This study compared the prevalences of metabolic syndrome and of cardiac or kidney comorbidities among patients with hepatocellular carcinoma (HCC) associated with metabolic dysfunction-related fatty liver disease (MAFLD), chronic infection with hepatitis B or C virus (HBV or HCV), or the combination of MAFLD and chronic HBV infection. METHODS: Medical records were retrospectively analyzed for patients with HCC who underwent hepatectomy between March 2013 and March 2023. Patients with HCC of different etiologies were compared in terms of their clinicodemographic characteristics and laboratory data before surgery. RESULTS: Of the 2422 patients, 1,822 (75.2%) were chronically infected with HBV without MAFLD and HCV, 415 (17.2%) had concurrent MAFLD and chronic HBV infection but no HCV infection, 121 (5.0%) had MAFLD without hepatitis virus infection, and 64 (2.6%) were chronically infected with HCV in the presence or absence of MAFLD and HBV infection. Compared to patients chronically infected with HBV without MAFLD and HCV, those with MAFLD but no hepatitis virus infection showed significantly lower prevalence of cirrhosis, ascites, portal hypertension, alpha-fetoprotein concentration ≥ 400 ng/mL, tumor size > 5 cm, multinodular tumors and microvascular invasion. Conversely, they showed significantly higher prevalence of metabolic syndrome, hypertension, type 2 diabetes, abdominal obesity, history of cardiovascular disease, T-wave alterations, hypertriglyceridemia and hyperuricemia, as well as higher risk of arteriosclerotic cardiovascular disease. Compared to patients with MAFLD but no hepatitis virus infection, those with concurrent MAFLD and chronic infection with HBV showed significantly higher prevalence of cirrhosis, ascites and portal hypertension, but significantly lower prevalence of hypertension and history of cardiovascular disease. Compared to patients with other etiologies, those chronically infected with HCV in the presence or absence of MAFLD and HBV infection, showed significantly higher prevalence of cirrhosis, portal hypertension, ascites, and esophagogastric varices. CONCLUSION: Patients with HCC associated with MAFLD tend to have a background of less severe liver disease than those with HCC of other etiologies, but they may be more likely to suffer metabolic syndrome or comorbidities affecting the heart or kidneys.