ACSL4 upregulates IFI44 and IFI44L expression and promotes the proliferation and invasiveness of head and neck squamous cell carcinoma cells.

Reprogramming of cellular energy metabolism, including deregulated lipid metabolism, is a hallmark of head and neck squamous cell carcinoma (HNSCC). However, the underlying molecular mechanisms remain unclear. Long-chain acyl-CoA synthetase 4 (ACSL4), which catalyzes fatty acids to form fatty acyl-CoAs, is critical for synthesizing phospholipids or triglycerides. Despite the differing roles of ACSL4 in cancers, our data showed that ACSL4 was highly expressed in HNSCC tissues, positively correlating with poor survival rates in patients. Knockdown of ACSL4 in HNSCC cells led to reduced cell proliferation and invasiveness. RNA sequencing analyses identified interferon-induced protein 44 (IFI44) and interferon-induced protein 44-like (IFI44L), encoded by two interferon-stimulated genes, as potential effectors of ACSL4. Silencing IFI44 or IFI44L expression in HNSCC cells decreased cell proliferation and invasiveness. Manipulating ACSL4 expression or activity modulated the expression levels of JAK1, tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 1 (STAT1), interferon α (IFNα), IFNß, and interferon regulatory factor 1 (IRF1), which regulate IFI44 and IFI44L expression. Knockdown of IRF1 reduced the expression of JAK1, TYK2, IFNα, IFNß, IFI44, or IFI44L and diminished cell proliferation and invasiveness. Our results suggest that ACSL4 upregulates interferon signaling, enhancing IFI44 and IFI44L expression and promoting HNSCC cell proliferation and invasiveness. Thus, ACSL4 could serve as a novel therapeutic target for HNSCC.

Temporally resolved proteomics identifies nidogen-2 as a cotarget in pancreatic cancer that modulates fibrosis and therapy response.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by increasing fibrosis, which can enhance tumor progression and spread. Here, we undertook an unbiased temporal assessment of the matrisome of the highly metastatic KPC (Pdx1-Cre, LSL-KrasG12D/+, LSL-Trp53R172H/+) and poorly metastatic KPflC (Pdx1-Cre, LSL-KrasG12D/+, Trp53fl/+) genetically engineered mouse models of pancreatic cancer using mass spectrometry proteomics. Our assessment at early-, mid-, and late-stage disease reveals an increased abundance of nidogen-2 (NID2) in the KPC model compared to KPflC, with further validation showing that NID2 is primarily expressed by cancer-associated fibroblasts (CAFs). Using biomechanical assessments, second harmonic generation imaging, and birefringence analysis, we show that NID2 reduction by CRISPR interference (CRISPRi) in CAFs reduces stiffness and matrix remodeling in three-dimensional models, leading to impaired cancer cell invasion. Intravital imaging revealed improved vascular patency in live NID2-depleted tumors, with enhanced response to gemcitabine/Abraxane. In orthotopic models, NID2 CRISPRi tumors had less liver metastasis and increased survival, highlighting NID2 as a potential PDAC cotarget.

Understanding the molecular crossroads in acute liver failure: A pathway to new therapies.

In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology. Acute liver failure (ALF) is a critical condition characterized by rapid hepatocellular injury and organ dysfunction, and it often necessitates liver transplant to ensure patient survival. Recent research has elucidated the involvement of distinct cell death pathways, namely ferroptosis and pyroptosis, in the pathogenesis of ALF. Ferroptosis is driven by iron-dependent lipid peroxidation, whereas pyroptosis is an inflammatory form of cell death; both pathways contribute to hepatocyte death and exacerbate tissue damage. This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF, highlighting the role of key regulators such as silent information regulator sirtuin 1. Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways. Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.

Unveiling significant risk factors for intensive care unit-acquired weakness: Advancing preventive care.

In this editorial, we discuss an article titled, "Significant risk factors for intensive care unit-acquired weakness: A processing strategy based on repeated machine learning," published in a recent issue of the World Journal of Clinical Cases. Intensive care unit-acquired weakness (ICU-AW) is a debilitating condition that affects critically ill patients, with significant implications for patient outcomes and their quality of life. This study explored the use of artificial intelligence and machine learning techniques to predict ICU-AW occurrence and identify key risk factors. Data from a cohort of 1063 adult intensive care unit (ICU) patients were analyzed, with a particular emphasis on variables such as duration of ICU stay, duration of mechanical ventilation, doses of sedatives and vasopressors, and underlying comorbidities. A multilayer perceptron neural network model was developed, which exhibited a remarkable impressive prediction accuracy of 86.2% on the training set and 85.5% on the test set. The study highlights the importance of early prediction and intervention in mitigating ICU-AW risk and improving patient outcomes.

Liver Resection Criteria for Patients with Hepatocellular Carcinoma and Multiple Tumors Based on Total Tumor Volume.

BACKGROUND: In many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits. METHODS: We reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan-Meier method. RESULTS: In all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria. CONCLUSION: Patients with TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria.

The Association between Cafestol and Cardiovascular Diseases: A Comprehensive Review.

Cafestol, a bioactive compound found in coffee, has attracted considerable attention due to its potential impact on cardiovascular health. This review aims to comprehensively explore the association between cafestol and cardiovascular diseases. We delve into the mechanisms through which cafestol influences lipid metabolism, inflammation, and endothelial function, all of which are pivotal in cardiovascular pathophysiology. Moreover, we meticulously analyze epidemiological studies and clinical trials to elucidate the relationship between cafestol and cardiovascular outcomes. Through a critical examination of existing literature, we aim to provide insights into the potential benefits and risks associated with cafestol concerning cardiovascular health.

Multi-gene phylogenetic and taxonomic contributions to Xylaria (Ascomycota) associated with fallen fruits from China.

Morphological and phylogenetic analyses on samples of Xylaria species associated with fallen fruits from China were carried out, and two new species were described, namely X.aleuriticola and X.microcarpa. Xylariaaleuriticola is found on fallen fruits of Aleuritesmoluccana, and characterized by stromata dichotomously branched several times with long acute sterile apices, fertile parts roughened with perithecia and tomentose, and ellipsoid to fusiform ascospores. Xylariamicrocarpa differs in its very small stromata with dark brown tomentum, light brown ascospores with an inconspicuous straight germ slit, and grows on leguminous pods. The differences between the new species and morphologically similar species are discussed. Phylogenetic analyses on ITS-RPB2-TUB sequences confirmed that the two species are clearly separated from other species of the genus Xylaria. Xylarialiquidambaris is reported as a new record from China. A key to the Xylaria species associated with fallen fruits and seeds reported from China is provided to facilitate future studies of the genus.

Effects of 3-year organic farming management on soil antibiotic resistant genes and virulence factors in a double rice cropping system.

Investigating the antibiotic resistance genes (ARGs) and virulence factors (VFs) within soil microbial communities is crucial for understanding microbial ecology and the evolution of antibiotic resistance. However, the study of ARGs, VFs, and their predominant microbial hosts in soils under varying rice production management practices remains largely underexplored. To this end, a three-year field experiment was conducted under organic management within a double rice cropping system in South China. The study revealed that, in contrast to conventional management (CK), organic farming practices did not significantly alter the total reads of ARGs and VFs. However, there was a notable alteration in the ARGs abundance at the antibiotic class level, such as an increase (P < 0.05) in the abundance of Multidrug ARGs (by 1.7 %) and a decrease (P < 0.05) in Rifamycin (by 17.5 %) and Fosfomycin ARGs (by 15.3 %). Furthermore, a significant shift in VFs was observed under organic farming compared to CK, characterized by an increase (P < 0.05) in offensive VFs and a decrease (P < 0.05) in nonspecific VFs and the regulation of virulence-associated genes. Key microbial taxa identified as influencing ARGs and VFs in the tested soil samples, e.g., Proteobacteria. The findings highlight the need for more detailed attention to soil ecology within organic rice production systems in South China, particularly concerning the significant alterations observed in ARGs and VFs.

Cascaded multicore fiber interferometers for enhanced bending sensing based on the Vernier effect.

In this paper, cascaded modal interferometers constructed by strongly-coupled seven-core fiber (SC-SCF) with different lengths are demonstrated for enhanced bending sensing based on Vernier effect. The free spectral range (FSR) of a single SC-SCF interferometer is determined by the length of SC-SCF. Two SC-SCF interferometers with different FSRs are cascaded, in which, one functions as the sensor while the other functions as the reference. The wavelength shift of the envelope of the output spectrum is much larger than that of a single SC-SCF interferometer due to the Vernier effect. Therefore, enhanced sensing can be achieved. Experimental results show that the bending sensitivity of the proposed sensor is improved from -2.20 nm/m-1 (single SC-SCF interferometer) to 42.32 nm/m-1 (cascaded SC-SCF interferometers). The temperature response of the sensor is also investigated. Our proposed cascaded SC-SCF sensor has advantages of high sensitivity, ease of fabrication, and low cost. It is attractive for high precision bending sensing applications.

Association between serum vitamin E and bacterial vaginitis in women: a cross-sectional study.

INTRODUCTION: Bacterial vaginitis (BV) is a common vaginal disease. Vitamin E has been shown to reduce BV by enhancing immune function, but no studies have analyzed the relationship between vitamin E and BV at different BMIs and ages. METHOD: This study used 2242 participants from four cycles of NHANES 1999-2006 in American. Participants' vitamin E levels were divided into four groups, and analyses such as study population description, stratified analysis, multiple logistic regression analysis, and curve fitting were performed. To perform data processing, the researchers used the statistical package R (The R Foundation; http://www.r-project.org ; version 3.6.3) and Empower Stats software ( www.empowerstats.net , X&Y solutions, Inc. Boston, Massachusetts). RESULT: The concentrations of serum vitamin E were negatively correlated with the risk of BV, especially when vitamin E were at 1198-5459ug/dL with (OR = -0.443, 95%CI = 0.447-0.923, P = 0.032) or without (OR = -0.521, 95%CI = 0.421-0.837, P = 0.006) adjustment for variables. At the same time, at lower levels, there was no significant association. Vitamin E supplementation may significantly reduce the risk of BV (p < 0.001). In addition, the risk of having BV decreased and then increased with increasing vitamin E concentrations at high BMI levels (p < 0.01). CONCLUSION: Vitamin E at moderate to high concentrations may significantly reduce BV risk, says the study, providing clinical evidence for the prevention and the treatment of BV.

Depression and risk of arthritis: A Mendelian randomization study.

INTRODUCTION: Observational studies have found that most patients with arthritis have depression. We aimed to determine the causal relationship between various types of arthritis and depression. METHODS: We conducted a two-sample bidirectional Mendelian randomized (MR) analysis to determine whether there was a significant causal relationship between depression and multiple types of arthritis. The data of our study were derived from the publicly released genome-wide association studies (GWASs) and the largest GWAS meta-analysis. MR analysis mainly used inverse-variance weighted method; supplementary methods included weighted median, weighted mode, and MR-Egger using MR pleiotropy residual sum and outlier to detect and correct for the presence of pleiotropy. RESULTS: After adjusting for heterogeneity and horizontal pleiotropy, we found that depression was associated with an increased risk of osteoarthritis (OA) (OR = 1.02, 95%CI: 1.01-1.02, p = 2.96 × E - 5). In the reverse analysis, OA was also found to increase the risk of depression (OR = 1.10, 95%CI: 1.04-1.15, p = .0002). Depression only increased the risk of knee OA (KOA) (OR = 1.25, 95%CI: 1.10-1.42, p = 6.46 × E - 4). Depression could potentially increase the risk of spondyloarthritis (OR = 1.52, 95%CI: 1.19-1.94, p ≤ 8.94 × E - 4). CONCLUSION: There is a bidirectional causal relationship of depression with OA. However, depression only augments the risk of developing KOA. Depression may increase the risk of spondyloarthritis and gout.

Combined associations of visceral adipose tissue and adherence to a Mediterranean lifestyle with T2D and diabetic microvascular complications among individuals with prediabetes.

BACKGROUND: It's unclear if excess visceral adipose tissue (VAT) mass in individuals with prediabetes can be countered by adherence to a Mediterranean lifestyle (MEDLIFE). We aimed to examine VAT mass, MEDLIFE adherence, and their impact on type 2 diabetes (T2D) and diabetic microvascular complications (DMC) in individuals with prediabetes. METHODS: 11,267 individuals with prediabetes from the UK Biobank cohort were included. VAT mass was predicted using a non-linear model, and adherence to the MEDLIFE was evaluated using the 25-item MEDLIFE index, encompassing categories such as "Mediterranean food consumption," "Mediterranean dietary habits," and "Physical activity, rest, social habits, and conviviality." Both VAT and MEDLIFE were categorized into quartiles, resulting in 16 combinations. Incident cases of T2D and related DMC were identified through clinical records. Cox proportional-hazards regression models were employed to examine associations, adjusting for potential confounding factors. RESULTS: Over a median follow-up of 13.77 years, we observed 1408 incident cases of T2D and 714 cases of any DMC. High adherence to the MEDLIFE, compared to the lowest quartile, reduced a 16% risk of incident T2D (HR: 0.84, 95% CI: 0.71-0.98) and 31% for incident DMC (0.69, 0.56-0.86). Conversely, compared to the lowest quartile of VAT, the highest quartile increased the risk of T2D (5.95, 4.72-7.49) and incident any DMC (1.79, 1.36-2.35). We observed an inverse dose-response relationship between MEDLIFE and T2D/DMC, and a dose-response relationship between VAT and all outcomes (P for trend < 0.05). Restricted cubic spline analysis confirmed a nearly linear dose-response pattern across all associations. Compared to individuals with the lowest MEDLIFE quartile and highest VAT quartile, those with the lowest T2D risk had the lowest VAT and highest MEDLIFE (0.12, 0.08-0.19). High MEDLIFE was linked to reduced T2D risk across all VAT categories, except in those with the highest VAT quartile. Similar trends were seen for DMC. CONCLUSION: High adherence to MEDLIFE reduced T2D and MDC risk in individuals with prediabetes, while high VAT mass increases it, but MEDLIFE adherence may offset VAT's risk partly. The Mediterranean lifestyle's adaptability to diverse populations suggests promise for preventing T2D.

exo-6b2-Methyl-Substituted Pentabenzocorannulene: Synthesis, Structural Analysis, and Properties.

exo-6b2-Methyl-substituted pentabenzocorannulene (exoPBC-Me) was synthesized by the palladium-catalyzed cyclization of 1,2,3-triaryl-1H-cyclopenta[l]phenanthrene. Its bowl-shaped geometry with an sp3 carbon atom in the backbone and a methyl group located at the convex (exo) face was verified by X-ray crystallography. According to DFT calculations, the observed conformer is energetically more favorable than the endo one by 39.9 kcal/mol. Compared to the nitrogen-doped analogs with intact π-conjugated backbones (see the main text), exo-PBC-Me displayed a deeper bowl depth (avg. 1.93 Å), redshifted and broader absorption (250-620 nm) and emission (from 585 to more than 850 nm) bands and a smaller optical HOMO-LUMO gap (2.01 eV). exo-PBC-Me formed polar crystals where all bowl-in-bowl stacking with close π···π contacts is arranged unidirectionally, providing the potential for applications as organic semiconductors and pyroelectric materials. This unusual structural feature, molecular packing, and properties are most likely associated with the assistance of the methyl group and the sp3 carbon atom in the backbone.

Sex differences in clinical characteristics and long-term clinical outcomes in Asian hospitalized heart failure patients.

AIMS: Sex differences in long-term post-discharge clinical outcomes in Asian patients hospitalized for acute decompensated heart failure (HF) persist despite the world-wide implementation of guideline-directed medical therapy for decades. The present study aims to elucidate the puzzling dilemma and to depict the directions of solution. METHODS AND RESULTS: Between 2011 and 2020, a total of 12 428 patients (6518 men and 5910 women, mean age 73.50 ± 14.85) hospitalized for acute decompensated HF were retrospectively enrolled from a university HF cohort. Compared with men, women hospitalized for acute decompensated HF were older in age (76.40 ± 13.43 vs. 71.20 ± 15.67 years old, P < 0.0001) with more coexisting hypertension, diabetes, hyperlipidaemia and moderate to severe chronic kidney disease, but less with ischaemic heart disease, cerebrovascular disease and chronic obstructive pulmonary disease (P < 0.0001). In echocardiography measurement parameters, women had smaller left ventricular and left atrial dimensions, higher left ventricular mass index, higher left ventricular ejection fraction (LVEF) and more in HF with preserved ejection fraction (EF) category (LVEF > 50%) than men (P < 0.0001). In HF therapy, women compared with men received more guideline-directed medical HF therapies including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter-2 inhibitors, but similar beta-blockers and mineralocorticoid receptor antagonists (P < 0.0001). Post-discharge long-term clinical outcomes after multivariate-adjusted analysis revealed that women compared with men had lower all-cause mortality [adjusted hazard ratio (aHR): 0.89, 95% confidence interval (CI): 0.84-0.93], lower cardiovascular mortality (aHR: 0.89, 95% CI: 0.80-0.99) and lower 1 year mortality (aHR: 0.91, 95% CI: 0.84-0.99) but similar HF rehospitalization rate (aHR: 1.02, 95% CI: 0.95-1.09) over 8 years of follow-up. The superiority of women over men in all-cause mortality was shown in HF with preserved EF (>50%) and HF with mildly reduced EF (40%-50%), but not in HF with reduced EF (<40%) category. Subgroup forest plot analysis showed body mass index, coexisting hypertension and chronic obstructive pulmonary disease as significant interacting factors. CONCLUSIONS: With more coronary risk factors and medical comorbidities, less cardiac remodelling and better adherence to guideline-directed HF therapy, women hospitalized for acute decompensated HF demonstrated superiority over men in long-term post-discharge clinical outcomes, including all-cause mortality, cardiovascular mortality and 1 year mortality, and mainly in HF with preserved and mid-range EF categories, in the Asian HF cohort.

Pd(II)/N,N'-Disulfonyl Bisimidazoline-Catalyzed Enantioselective Synthesis of Cyclic Quaternary Centers and Mechanistic Investigations.

A Pd(II)/N,N'-disulfonyl bisimidazoline-catalyzed asymmetric 1,4-conjugate addition reaction of low-cost arylboronic acids with readily available ß-substituted cyclic enones is described, providing a straightforward way of constructing cyclic all-carbon quaternary stereocenters with high enantioselectivity, in which ≥96% ee was obtained in most cases. The reaction proceeded without the protection of inert gas, making the operation process simple. Theoretical calculations have been applied to understand the origins of enantioselectivity.

The shared circulating diagnostic biomarkers and molecular mechanisms of systemic lupus erythematosus and inflammatory bowel disease.

Background: Systemic lupus erythematosus (SLE) is a multi-organ chronic autoimmune disease. Inflammatory bowel disease (IBD) is a common chronic inflammatory disease of the gastrointestinal tract. Previous studies have shown that SLE and IBD share common pathogenic pathways and genetic susceptibility, but the specific pathogenic mechanisms remain unclear. Methods: The datasets of SLE and IBD were downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using the Limma package. Weighted gene coexpression network analysis (WGCNA) was used to determine co-expression modules related to SLE and IBD. Pathway enrichment was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for co-driver genes. Using the Least AbsoluteShrinkage and Selection Operator (Lasso) regressionand Support Vector Machine-Recursive Feature Elimination (SVM-RFE), common diagnostic markers for both diseases were further evaluated. Then, we utilizedthe CIBERSORT method to assess the abundance of immune cell infiltration. Finally,we used the single-cell analysis to obtain the location of common diagnostic markers. Results: 71 common driver genes were identified in the SLE and IBD cohorts based on the DEGs and module genes. KEGG and GO enrichment results showed that these genes were closely associated with positive regulation of programmed cell death and inflammatory responses. By using LASSO regression and SVM, five hub genes (KLRF1, GZMK, KLRB1, CD40LG, and IL-7R) were ultimately determined as common diagnostic markers for SLE and IBD. ROC curve analysis also showed good diagnostic performance. The outcomes of immune cell infiltration demonstrated that SLE and IBD shared almost identical immune infiltration patterns. Furthermore, the majority of the hub genes were commonly expressed in NK cells by single-cell analysis. Conclusion: This study demonstrates that SLE and IBD share common diagnostic markers and pathogenic pathways. In addition, SLE and IBD show similar immune cellinfiltration microenvironments which provides newperspectives for future treatment.

Neuroimmunological effects of omega-3 fatty acids on migraine: a review.

Migraine is a highly prevalent disease worldwide, imposing enormous clinical and economic burdens on individuals and societies. Current treatments exhibit limited efficacy and acceptability, highlighting the need for more effective and safety prophylactic approaches, including the use of nutraceuticals for migraine treatment. Migraine involves interactions within the central and peripheral nervous systems, with significant activation and sensitization of the trigeminovascular system (TVS) in pain generation and transmission. The condition is influenced by genetic predispositions and environmental factors, leading to altered sensory processing. The neuroinflammatory response is increasingly recognized as a key event underpinning the pathophysiology of migraine, involving a complex neuro-glio-vascular interplay. This interplay is partially mediated by neuropeptides such as calcitonin gene receptor peptide (CGRP), pituitary adenylate cyclase activating polypeptide (PACAP) and/or cortical spreading depression (CSD) and involves oxidative stress, mitochondrial dysfunction, nucleotide-binding domain-like receptor family pyrin domain containing-3 (NLRP3) inflammasome formation, activated microglia, and reactive astrocytes. Omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), crucial for the nervous system, mediate various physiological functions. Omega-3 PUFAs offer cardiovascular, neurological, and psychiatric benefits due to their potent anti-inflammatory, anti-nociceptive, antioxidant, and neuromodulatory properties, which modulate neuroinflammation, neurogenic inflammation, pain transmission, enhance mitochondrial stability, and mood regulation. Moreover, specialized pro-resolving mediators (SPMs), a class of PUFA-derived lipid mediators, regulate pro-inflammatory and resolution pathways, playing significant anti-inflammatory and neurological roles, which in turn may be beneficial in alleviating the symptomatology of migraine. Omega-3 PUFAs impact various neurobiological pathways and have demonstrated a lack of major adverse events, underscoring their multifaceted approach and safety in migraine management. Although not all omega-3 PUFAs trials have shown beneficial in reducing the symptomatology of migraine, further research is needed to fully establish their clinical efficacy and understand the precise molecular mechanisms underlying the effects of omega-3 PUFAs and PUFA-derived lipid mediators, SPMs on migraine pathophysiology and progression. This review highlights their potential in modulating brain functions, such as neuroimmunological effects, and suggests their promise as candidates for effective migraine prophylaxis.

Oncological outcomes post transoral robotic surgery (TORS) for HPV-associated oropharyngeal squamous cell carcinoma, a single-centre retrospective Australian study.

We present a cohort review of TORS resection for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and its associated oncological outcomes spanning a 10-year period. A retrospective case series review was performed of patients undergoing primary surgical treatment for HPV-associated OPSCC through the St. Vincent's Head and Neck Cancer service from 2011 to 2022. The primary outcomes were to investigate complete resection of the primary tumour, rates of recurrence, and survival analysis. Secondary outcomes included complications, rates of adjuvant therapy, sites of recurrence and rates of percutaneous endoscopic gastrostomy (PEG). 184 patients underwent TORS-based therapy with neck dissection, and guideline-directed adjuvant therapy for HPV-associated OPSCC. Our median follow-up was 46 months. The positive margin rate on final histopathology analysis was 10.9%. Adjuvant therapy was indicated in 85 patients (46%). The local recurrence rate was 10.9% with the majority (80%) of patients recurring in the first 3 years since treatment. The disease-specific survival at 3 years was 98.6% and at 5 years was 94.4%. The 3-year and 5-year OS for the cohort was 96.7% and 92.5%, respectively. The presence of extranodal extension and positive margins were associated with increased risk of recurrence, whereas adjuvant therapy was found to be a protective factor for both overall recurrence and survival. Major complications occurred in 12 patients (6.5%), resulting in one death. This study has demonstrated that primary surgical therapy for HPV-associated OPSCC is a safe and effective treatment modality with low local recurrence and complication rates, and overall survival benefits.

A three-dimensional spring-loaded inverted pendulum walking model considering human movement speed and frequency.

The spring-loaded inverted pendulum (SLIP) model is an effective model to capture the essential dynamics during human walking and/or running. However, most of the existing three-dimensional (3D) SLIP model does not explicitly account for human movement speed and frequency. To address this knowledge gap, this paper develops a new SLIP model, which includes a roller foot, massless spring, and concentrated mass. The governing equations-of-motion for the SLIP model during its double support phase are derived. It is noted that in the current formulation, the motion of the roller foot is prescribed; therefore, only the equations for the concentrated mass need to be solved. To yield model parameters leading to a periodic walking gait, a constrained optimization problem is formulated and solved using a gradient-based approach with a global search strategy. The optimization results show that when the attack angle ranges from 68° to 74°, the 3D SLIP model can yield a periodic walking gait with walking speeds varying from 0.5 to 2.0 m s-1. The predicted human walking data are also compared with published experimental data, showing reasonable accuracy.

Impact of healthy lifestyle on the incidence and progression trajectory of mental disorders: A prospective study in the UK Biobank.

BACKGROUND: Healthier lifestyle decreased the risk of mental disorders (MDs) such as depression and anxiety. However, research on the effects of a comprehensive healthy lifestyle on their progression is lacking. METHODS: 385,704 individuals without baseline MDs from the UK Biobank cohort were included. A composite healthy lifestyle score was computed by assessing alcohol intake, smoking status, television viewing time, physical activity, sleep duration, fruit and vegetable intake, oily fish intake, red meat intake, and processed meat intake. Follow-up utilized hospital and death register records. Multistate model was used to examine the role of healthy lifestyle on the progression of specific MDs, while a piecewise Cox regression model was utilized to assess the influence of healthy lifestyle across various phases of disease progression. RESULTS: Higher lifestyle score reduced risks of transitions from baseline to anxiety and depression, as well as from anxiety and depression to comorbidity, with corresponding hazard ratios (HR) and 95 % confidence intervals (CI) of 0.94 (0.93, 0.95), 0.90 (0.89, 0.91), 0.94 (0.91, 0.98), and 0.95 (0.92, 0.98), respectively. Healthier lifestyle decreased the risk of transitioning from anxiety to comorbidity within 2 years post-diagnosis, with HR 0.93 (0.88, 0.98). Higher lifestyle scores at 2-4 years and 4-6 years post-depression onset were associated with reduced risk of comorbidity, with HR 0.93 (0.87, 0.99) and 0.92 (0.86, 0.99), respectively. LIMITATION: The generalizability to other ethnic groups is limited. CONCLUSION: This study observed a protective role of holistic healthy lifestyle in the trajectory of MDs and contributed to identifying critical progression windows.