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The development of new analog computers based on analog signals of electromagnetic or elastic waves has become a hot research topic in recent years. In this Letter, based on the concept of quantum state transfer, we study the process of energy transfer between acoustic cavities. Through the transformation from the temporal domain to the spatial domain, we further study the process of energy transfer between acoustic waveguides, and then we realize the applications of energy distributors and limiters in the acoustic system, which are the functional devices of wireless communication technology in new analog acoustic computers. We both simulationlly and experimentally demonstrate the effectiveness of the two applications. The energy distributor and limiter we proposed have the advantages of a relatively wide operating frequency range and adjustability. Our work shows the transfer mechanism of acoustic energy between different structures, which increases its potential application value in new analog acoustic computers. [ABSTRACT FROM AUTHOR]

Acoustic levitation is widely used in non-container measurement and non-contact manipulation. Particles in the single-axis acoustic levitation are easily unstable in the radial direction under external perturbations. In order to explore the instability in the acoustic levitation during radial perturbations, a nonlinear acoustic levitation model considering the coupling of radial and axial vibration is proposed to analyze the dominant factors influencing the levitation stability, an acoustic levitation system consisting of a transducer and a plane reflector is established, and high-speed photography is used to observe the vibration behavior of the particle with large radial vibration and the levitation stability. The simulation results are compared and verified with the experiments, which indicate that the reduction in axial trapping stiffness due to radial vibration plays a vital role in the levitation instability. The present model can characterize the radial anti-interference ability of different levitators as well as predict the movement trajectories of levitated particles after being disturbed, which is helpful to optimize the design of acoustic levitators and provide guidance for acoustic manipulation. [ABSTRACT FROM AUTHOR]

Terahertz (THz) light, probing electronic responses near the Fermi level, is closely linked to DC transport. In this study, we investigate the in situ THz and DC conductivity of epitaxial VO 2 films near the heating-induced insulator–metal transition. We find that the THz conductivity transition occurs at lower temperatures than the DC conductivity transition, with the separation increasing with film thickness and crystallization quality. Analysis of the complex conductivity spectra attributes this separation to released carrier confinement at THz frequencies. Our findings contribute to a deeper understanding of electron dynamics in VO 2 films. [ABSTRACT FROM AUTHOR]

In the previous paper [C. W. Kim and I. Franco, J. Chem. Phys. 160, 214111-1–214111-13 (2024)], we developed a theory called MQME-D, which allows us to decompose the overall energy dissipation process in open quantum system dynamics into contributions by individual components of the bath when the subsystem dynamics is governed by a Markovian quantum master equation (MQME). Here, we contrast the predictions of MQME-D against the numerically exact results obtained by combining hierarchical equations of motion (HEOM) with a recently reported protocol for monitoring the statistics of the bath. Overall, MQME-D accurately captures the contributions of specific bath components to the overall dissipation while greatly reducing the computational cost compared to exact computations using HEOM. The computations show that MQME-D exhibits errors originating from its inherent Markov approximation. We demonstrate that its accuracy can be significantly increased by incorporating non-Markovianity by exploiting time scale separations (TSS) in different components of the bath. Our work demonstrates that MQME-D combined with TSS can be reliably used to understand how energy is dissipated in realistic open quantum system dynamics. [ABSTRACT FROM AUTHOR]

We present a general and practical theoretical framework to investigate how energy is dissipated in open quantum system dynamics. This is performed by quantifying the contributions of individual bath components to the overall dissipation of the system. The framework is based on the Nakajima–Zwanzig projection operator technique, which allows us to express the rate of energy dissipation into a specific bath degree of freedom by using traces of operator products. The approach captures system-bath interactions to all orders, but is based on second-order perturbation theory on the off-diagonal subsystem's couplings and a Markovian description of the bath. The usefulness of our theory is demonstrated by applying it to various models of open quantum systems involving harmonic oscillators or spin baths and connecting the outcomes to existing results such as our previously reported formula derived for locally coupled harmonic baths [Kim and Franco, J. Chem. Phys. 154, 084109 (2021)]. We also prove that the dissipation calculated by our theory rigorously satisfies thermodynamic principles such as energy conservation and detailed balance. Overall, the strategy can be used to develop the theory and simulation of dissipation pathways to interpret and engineer the dynamics of open quantum systems. [ABSTRACT FROM AUTHOR]

A method for characterizing the topological fluctuations in liquids is proposed. This approach exploits the concept of the weighted gyration tensor of a collection of particles and permits the definition of a local configurational unit (LCU). The first principal axis of the gyration tensor serves as the director of the LCU, which can be tracked and analyzed by molecular dynamics simulations. Analysis of moderately supercooled Kob–Andersen mixtures suggests that orientational relaxation of the LCU closely follows viscoelastic relaxation and exhibits a two-stage behavior. The slow relaxing component of the LCU corresponds to the structural, Maxwellian mechanical relaxation. Additionally, it is found that the mean curvature of the LCUs is approximately zero at the Maxwell relaxation time with the Gaussian curvature being negative. This observation implies that structural relaxation occurs when the configurationally stable and destabilized regions interpenetrate each other in a bicontinuous manner. Finally, the mean and Gaussian curvatures of the LCUs can serve as reduced variables for the shear stress correlation, providing a compelling proof of the close connection between viscoelastic relaxation and topological fluctuations in glass-forming liquids. [ABSTRACT FROM AUTHOR]

Background: Robot-assisted rehabilitation is considered beneficial for functional recovery in patients with stroke, but the therapeutic effect remains inconclusive. The present study investigated the therapeutic effects of gait training assisted by a user-initiated powered exoskeletal robot (UIPER) in patients in the early stage after stroke. We also characterized patients' improvement by analyzing chronological changes in clinical measurements together with gait parameters obtained from internal sensors in the exoskeletal robot. Methods: In this pilot case-controlled study, 17 and 81 patients with stroke onset durations of < 3 months were included in the robot-assisted combined with conventional treatment (RT + CT) group and conventional treatment only (CT) group, respectively. The UIPER, which provides knee flexion and extension support and has hip and knee sensors, was applied to guide gait performance in the RT + CT group. The patients in the RT + CT group received robot-assisted gait training for 40 min/ session, 1 session a day, and 2–3 sessions a week (6 sessions in total). The primary outcome was the proportion of patients reaching the minimum clinically important difference (MCID) in the 5-meter walking speed (5MWS) assessment, and the secondary outcomes were the MCID for the six-minute walking test, the Berg Balance Scale, the Barthel Index, the Fugl-Meyer assessment, and the timed up and go test before, during, and after the interventions. Gait parameters of the hip and knee were evaluated at baseline, midterm, and final sessions. Results: Gait function improved in both groups after the intervention (both P < 0.05). The primary outcome showed that a greater proportion of patients reached the MCID for the 5MWS in the RT + CT group than in the CT group (70.6 vs. 43.2%, P = 0.040; = 0.208). Similarly, in terms of the secondary outcomes, more patients in the RT + CT group reached the MCID for the Barthel index as compared with the CT group (41.2 vs. 17.3%, P = 0.047, = 0.220). Gait analysis revealed improvements in gait in the RT + CT group, as indicated by increases in the perimeter and area of the hip–knee cyclogram, as well as the range of motion in the hip joint. Conclusions: Gait training assisted by UIPER facilitates the recovery of walking speed and activities of daily living in patients with stroke, and these improvements may be related to improvements in gait parameters. Randomized controlled studies with larger sample sizes are needed to confirm these findings. Trial registration: This trial was approved by the Institutional Review Board of Chang Gung Medical Foundation (No. 202200822B0). [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions Notable advances have been made in immune checkpoint inhibitors (ICIs) for cancer treatment. However, the adverse effects of ICIs, especially hepatotoxicity, remain a challenging problem. Whether patients in hepatitis B virus (HBV)‐endemic areas are prone to developing hepatic adverse events during ICI treatment warrants further exploration.From 2014 to 2020, the data of all patients with cancer who received ICI treatment at Taipei Veterans General Hospital were retrospectively reviewed. The incidence of and risk factors for hepatic adverse events, including hepatitis flare, immune‐related hepatitis (irHepatitis) and HBV reactivation (HBVr), were analysed through a Cox proportional hazard regression model.A total of 1283 patients with cancer (190 hepatocellular carcinoma [HCC] patients and 1093 patients with non‐HCC malignancies) were eligible for analysis, of whom 283 (22.1%) were HBsAg‐positive. The incidence of hepatitis flare events of any grade was significantly higher in HCC patients than in non‐HCC patients (45.8% vs. 25.6%, p < 0.001). HCC and baseline alanine aminotransferase (ALT) > 40 U/L were independent risk factors for ≥ grade 3 hepatitis flare events. No difference was observed in irHepatitis risk between HCC patients and non‐HCC patients. ALT > 40 U/L was an independent risk factor for irHepatitis. Among 283 HBsAg‐positive patients, six patients (2.1%) experienced HBVr. HCC patients had a higher risk of HBVr than non‐HCC patients (4.4% vs. 0.6%). No specific risk factor for HBVr could be identified. However, none of the patients under nucleos/tide analogue (NUC) prophylaxis experienced HBVr in this study.Under ICI treatment, HCC patients had a higher risk of hepatitis flare events than non‐HCC patients. Abnormal baseline ALT levels are a risk factor for hepatic adverse events. NUC prophylaxis can minimise the risk of HBVr. [ABSTRACT FROM AUTHOR]

A novel series of damped multistep formulas of matrix coefficients are developed to find the solutions of dynamic problems with negligible stiff components or eigenmodes. They are derived from the concept of eigenmode and the development details are presented. A total of six multistep formulas is developed and they have an order of accuracy from 1 to 6 corresponding to the 1-step to 6-step multistep formula. Each formula has damping to suppress or remove the stiff components or eigenmodes that are of no importance or of no interest while the slow eigenmode solutions can be still accurately calculated. The 1-step and 2-step formulas of the series are L-stable. Besides, each formula can have a non-iterative solution procedure and hence it is of high computational efficiency in contrast to the corresponding conventional backward differentiation method. This series can give a better quality of numerical solutions for dynamic problems with negligible stiff components or eigenmodes when compared to the methods with no damping. Numerical tests reveal that this series performs well like the backward differentiation method and it can save many efforts in computing if a non-iterative solution procedure is used when compared to the backward differentiation method. [ABSTRACT FROM AUTHOR]

Incomplete Atypical Femoral Fracture (IAFF) is a precursor to Atypical Femoral Fracture (AFF). If untreated, it progresses to a complete fracture, increasing mortality risk. However, due to their small and ambiguous features, IAFFs are often misdiagnosed even by specialists. In this paper, we propose a novel approach for accurately classifying IAFFs in X-ray images across various radiographic views. We design a Dual Context-aware Complementary Extractor (DCCE) to capture both the overall femur characteristics and IAFF details with the surrounding context, minimizing information loss. We also develop a Level-wise Perspective-preserving Fusion Network (LPFN) that preserves the perspective of features while integrating them at different levels to enhance model representation and sensitivity by learning complex correlations and features that are difficult to obtain independently. Additionally, we incorporate the Spatial Anomaly Focus Enhancer (SAFE) to emphasize anomalous regions, preventing the model bias toward normal regions, and reducing False Negatives and missed IAFFs. Experimental results show significant improvements across all evaluation metrics, demonstrating high reliability in terms of accuracy (0.931), F1-score (0.9456), and AUROC (0.9692), proving the model's potential for application in real medical settings. [ABSTRACT FROM AUTHOR]

Liver metastases are commonly detected in the advanced stages of various malignant tumors, representing a significant clinical challenge. Throughout the process of liver metastases formation, immune cells play a pivotal role, particularly in the pre-metastatic and metastatic niches within the liver. Immune cells establish extensive and intricate interactions with tumor cells and other components in the liver, collectively promoting and sustaining the growth of liver metastases. Despite the limited efficacy of existing therapeutic modalities against some advanced liver metastases, novel immune-based treatment approaches are continuously being explored and validated. Building on the systematic elucidation of the immunosuppressive characteristics of liver metastases, we explored the potential of novel immunotherapies applicable to patients with liver metastases from multiple dimensions. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is hypothesized to be associated with accelerated biological aging. Telomere length (TL) is a biomarker of aging, and although TL decreases with each cell division, the rate of telomere shortening may be affected by inflammation. We aimed to investigate whether TL is decreased in BD patients and to determine the association between TL and inflammatory markers in such patients. 137 BD patients and 118 healthy controls (HCs) were recruited. Leukocyte TL and plasma levels of cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-8, IL-6, IL-10, transforming growth factor (TGF)-β1], C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF) were assessed. TL did not differ significantly between the BD patients and HCs after adjustment for potential confounding factors (P = 0.79). TL was significantly negatively associated with age (β = −0.007, P < 0.001). In addition, log TNF-α levels were significantly negatively associated with TL (P = 0.009), in both the BD patients (P = 0.02) and HCs (P = 0.05). We found a significant association between TNF-α levels and TL shortening in both BD patients and HCs. However, BD patients did not display increased TL shortening relative to HCs. Studies that involve larger sample sizes and control for the heterogeneity of BD participants will be needed. • Bipolar disorder patients may not have telomere length shortening • Plasma tumor necrosis factor-α levels may be associated with telomere length shortening • Bipolar disorder subtypes and mood states may not relate to telomere length shortening [ABSTRACT FROM AUTHOR]

Background: Anxiety and depressive disorders, characterized by high incidence and functional impairments, are emotional disorders with shared etiological and maintenance mechanisms. Dialectical behavior therapy (DBT) is a promising approach for the transdiagnostic treatment of emotional disorders. Developing a brief DBT intervention can facilitate the adoption of evidence-based therapy. Methods: This protocol is for a 3-year single-blinded, two-arm randomized controlled trial. Individuals with depressive or anxiety disorder will be randomly allocated to a modified DBT–informed transdiagnostic psychotherapy group or a treatment-as-usual group. The intervention group will receive DBT individual therapy for 15 weeks. Power analyses revealed that the cohort should include a minimum of 250 participants. Preintervention, postintervention, and follow-up (after 3 months) assessments will be conducted. Primary outcomes will be severities of depression and anxiety rated by blind assessors. Intent-to-treat and per-protocol analyses will be conducted using the hierarchical linear model. Effect sizes will be estimated using Cohen's d. Result: To the best of our knowledge, the proposed study will be the first randomized controlled trial to evaluate the efficacy of a modified DBT intervention in managing transdiagnostic emotional disorders in Chinese individuals. Conclusion: This intervention is expected to improve clinical outcomes, daily functioning, and quality of life. The trial will enrich the empirical evidence for transdiagnostic interventions, facilitating the implementation of evidence-based therapy and reducing the high prevalence and challenges (e.g., disability) of emotional disorders in the Chinese population. Trial registration number: NCT05989451 [ABSTRACT FROM AUTHOR]

Background: Hypofunction of the glutamate system in the brain is one of the pathophysiological hypotheses for schizophrenia. Accumulating animal and clinical studies show that sarcosine (N-methylglycine), a glycine transporter-1 inhibitor, is effective in ameliorating the negative and cognitive symptoms of schizophrenia. The aims of the present study were to observe the effects of sarcosine on neuronal activity in the dorsal CA1 (dCA1) hippocampal neurons within an NMDA receptor hypofunction model induced by MK801. Methods: We applied in vivo calcium imaging to observe the dynamics of fluorescence from the dCA1 hippocampal neurons when the mice were exploring in an open field. Using this tool, we directly measured and compared neuronal properties between sarcosine-treated and untreated mice. At the same time, the physiological function of the neurons was also quantified by measuring their place fields. Results: Our data demonstrated that MK-801 (0.2 mg/kg) diminished the fluorescence intensity of dCA1 neurons that had been genetically modified with a calcium indicator. MK-801 also significantly increased the correlation coefficient between the fluorescence dynamics of pairs of cells, a feature that may be linked to the symptom of disorganization in human patients with schizophrenia. The spatial correlations of place fields in the mice were impaired by MK-801 as well. Injected sarcosine (500 mg or 1000 mg/kg) significantly alleviated the abovementioned abnormalities. Conclusions: Our data provide evidence to support the use of sarcosine to alleviate symptoms of schizophrenia, especially hippocampus-related functions. [ABSTRACT FROM AUTHOR]

Objectives: Biological disease‐modifying antirheumatic drugs have been the primary treatment option for moderate to severe rheumatoid arthritis (RA) in Taiwan since 2010. Tocilizumab is an interleukin‐6 receptor inhibitor, whereas tofacitinib is a Janus kinase inhibitor. The two medications were indicated to treat RA by direct and indirect inhibition of interleukin‐6 cytokine. We compared the safety outcomes of tocilizumab and tofacitinib in patients with RA in real‐world clinical settings, following the 7 key components of target trial emulation (TTE). Methods: The data source was the Taiwan National Health Insurance Research Database. Patients with RA between 2010 and 2018 were eligible and assigned to either tocilizumab or tofacitinib based on their first prescription of these two medications. The index date was set as the first prescription date of either study medication. Propensity score stabilized weighting (PSSW) was used to balance the characteristics between the two medication groups. The incidences of safety outcomes were all‐cause mortality, cancer, coronary heart disease, stroke, venous thrombosis events, tuberculosis, joint replacement events, and herpes zoster infection. The intention‐to‐treat (ITT) effect was commenced from the index date until the study outcomes, independently, 3 years, withdrawal, or December 31, 2021, whichever occurred first. For the per‐protocol (PP) effect, patients were required to maintain the same medical group during the entire follow‐up period. Results: A total of 2125 patients with RA who were prescribed tocilizumab (n = 844) or tofacitinib (n = 1281) were included in this study. The mean follow‐up duration was 2.78 years in the tocilizumab group and 2.83 years in the tofacitinib group. For ITT, the sample sizes were 721 and 1196 for the tocilizumab and tofacitinib, respectively, after PSSW. A substantially lower incidence rate of herpes zoster infection (per 100 patient‐years) was observed in the tocilizumab group (3.67) than in the tofacitinib group (7.61), with a hazard ratio of 0.48 (95%CI =0.37–0.63; p <.0001). All‐cause mortality, cancer, coronary heart disease, stroke, total hip replacement, and tuberculosis were similar between the two medication groups. For PP, the sample sizes were 619 and 1085 for the tocilizumab and tofacitinib, respectively, after PSSW. The results of the PP analysis were similar to those of the ITT analysis. Conclusions: Tocilizumab and tofacitinib act along the same inflammatory pathway. A lower herpes zoster incident rate was observed in the tocilizumab group than in the tofacitinib group. The incidence rates of other safety concerns and mortality rates were comparable in both groups of patients with RA treated in real‐world settings. [ABSTRACT FROM AUTHOR]

Aim: Ergostatrien‐3β‐ol (EK100) is a bioactive compound found in the fruiting bodies and mycelia of Antrodia cinnamomea and has anti‐inflammatory and immunomodulatory properties. This study aims to evaluate the potential of EK100 as a treatment for Sjögren's syndrome (SS). Methods: We employed a spontaneous SS model in non‐obese diabetic (NOD)/Ltj mice to assess the therapeutic potential of EK100. The effects of EK100 were evaluated based on stimulated salivary flow rates, sialadenitis, expression of inflammatory cytokines in salivary glands, and profiles of T cell subsets in the spleen. Additionally, in vitro experiments were conducted to assess the impact of EK100 on Th17 cell differentiation and dendritic cell (DC) maturation. Results: EK100 treatment significantly increased salivary flow rates, suppressed lymphocyte infiltration, and decreased the concentrations of anti‐SSA/Ro and anti‐SSB/La autoantibodies. EK100 also downregulated the expression of various inflammatory cytokines in the salivary glands and reduced the populations of Th1 and Th17 cells in the spleens of NOD/Ltj mice. In vitro experiments confirmed that EK100 inhibited the differentiation of Th17 cells and the maturation of DCs. Conclusion: Our findings suggest that EK100 may offer a promising therapeutic avenue for the treatment of SS by modulating the interaction between Th17 cells and DCs. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions. METHODS: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial. Immediate postpolypectomy bleeding (IPPB), defined as the perioperative use of a clip for bleeding, was evaluated through polyp-level analysis. Delayed postpolypectomy bleeding (DPPB), defined as bleeding occurring within 2 weeks postoperatively, was assessed at the patient-level among patients whose polyps were all ≤10 mm, including at least one 0-Ip polyp. RESULTS: A total of 647 0-Ip polyps (CSP: 306; HSP: 341) were included for IPPB analysis and 386 patients (CSP: 192; HSP: 194) for DPPB analysis. CSP was associated with a higher incidence of IPPB (10.8% vs 3.2%, P < 0.001) but no adverse clinical events. The procedure time of all polypectomies was shorter for CSP than for HSP (123.0 ± 117.8 vs 166.0 ± 237.7 seconds, P = 0.003), while the procedure time of polypectomies with IPPB were similar (249.8 ± 140.2 vs 227.4 ± 125.9 seconds, P = 0.64). DPPB was observed in 3 patients (1.5%) in the HSP group, including one patient (0.5%) with severe bleeding, but not in the CSP group. DISCUSSION: Despite CSP being associated with more IPPB events, it could be timely treated without adverse outcomes. Notably, no delayed bleeding occurred in the CSP group. Our findings support the use of CSP for 0-Ip polyps ≤ 10 mm. [ABSTRACT FROM AUTHOR]

Background: Clinical trials have shown the kidney‐protective benefits of sodium‐glucose cotransporter 2 inhibitors (SGLT2i). However, their real‐world impact, particularly across varying levels of albuminuria, remains less well understood. This study aimed to evaluate the association of SGLT2i, compared with other oral glucose‐lowering drugs, with end‐stage kidney disease (ESKD) progression in patients with type 2 diabetes and chronic kidney disease (CKD) stratified by urine albumin‐to‐creatinine ratio (UACR) levels. Methods: Using data from a national database spanning from 2016 to 2021, the study included patients with type 2 diabetes and CKD with estimated glomerular filtration rates (eGFRs) below 60 mL/min/1.73 m2 and who started on SGLT2i or other oral glucose‐lowering drugs. Patients were stratified into groups by UACR ≥300 mg/g and <300 mg/g. Propensity score matching was used to minimize confounding, and progression to ESKD was evaluated using competing risks and Cox proportional‐hazards models. All‐cause mortality was also analyzed. Results: Following propensity score matching, 18,514 patients in the severely increased albuminuria group (UACR ≥300 mg/g) were tracked, with 2.6% progressing to ESKD over 3 years. In contrast, only 0.3% of the 26,946 patients with UACR <300 mg/g progressed to ESKD. SGLT2i use was associated with a 30% reduction in risk of ESKD progression, compared with the use of other oral glucose‐lowering drugs, in the severely increased albuminuria group (hazard ratio[HR]: 0.70, 95% confidence interval [CI]: 0.61–0.80). In the lower albuminuria group, no significant association was evident, though there was a nonsignificant trend toward protection over time. A consistent reduction in mortality risk was observed across all albuminuria levels. Conclusions: SGLT2i are associated with a reduction in the progression to ESKD among patients with severely increased albuminuria, with less pronounced effects observed in those with lower albuminuria levels, suggesting variability in renal outcomes based on albuminuria severity. The consistent survival benefit across all albuminuria levels supports the potential utility of SGLT2i in diabetes and CKD treatment strategies, emphasizing the need for more targeted research. [ABSTRACT FROM AUTHOR]

Introduction: The comparison between the cementless taper wedge stem and fit-and-fill stem in total hip arthroplasty (THA) for various proximal femoral morphological types has not been thoroughly assessed. This study aimed to compare the risk of leg length discrepancy (LLD) ≥ 10 mm between these two stem types in Dorr type A, B, and C femurs. Materials and methods: From April 2015 through April 2021, we analyzed 1178 unilateral primary cementless THA procedures. We categorized all procedures into three groups: Dorr type A (N = 220, 18.7%), B (N = 875, 74.3%), and C (N = 83, 7.0%). Within each Dorr type, we compared the incidence and risk of postoperative LLD ≥ 10 mm between the two stem types. The factors considered in the multivariate regression analyses included stem type, age, sex, body mass index, diagnosis, canal flare index, femoral cortical index and stem alignment. Results: The taper wedge stem group had a higher overall incidence of LLD ≥ 10 mm (12.8% vs. 7.4%, P = 0.012) and in Dorr type A femurs (22.2% vs. 7.6%, P = 0.014), compared with the fit-and-fill stem group. In multivariate analysis, the taper wedge stem exhibited an increased risk of LLD ≥ 10 mm only in Dorr type A femurs (aOR: 3.449, 95% CI: 1.325–8.794). The incidence and risk of LLD ≥ 10 mm were not different between the two stems in Dorr type B and C femurs. Conclusions: The taper wedge stem demonstrated an elevated risk of LLD ≥ 10 mm in Dorr type A femurs compared with the fit-and-fill stem, necessitating meticulous preoperative templating and intraoperative femoral canal preparation. [ABSTRACT FROM AUTHOR]

Branched-chain amino acids (BCAAs) are essential for muscle protein synthesis and are widely acknowledged for mitigating sarcopenia. Oligonol® (Olg), a low-molecular-weight polyphenol from Litchi chinensis, has also been found to attenuate sarcopenia by improving mitochondrial quality and positive protein turnover. This study aims to investigate the effect of Olg on BCAA-stimulated protein synthesis in sarcopenia. In sarcopenic C57BL/6 mice and senescence-accelerated mouse-prone 8 (SAMP8) mice, BCAAs were significantly decreased in skeletal muscle but increased in blood serum. Furthermore, the expressions of membrane L-type amino acid transporter 1 (LAT1) and branched-chain amino acid transaminase 2 (BCAT2) in skeletal muscle were lower in aged mice than in young mice. The administration of Olg for 8 weeks significantly increased the expressions of membrane LAT1 and BCAT2 in the skeletal muscle when compared with non-treated SAMP8 mice. We further found that BCAA deprivation via LAT1-siRNA in C2C12 myotubes inhibited the signaling of protein synthesis and facilitated ubiquitination degradation of BCAT2. In C2C12 cells mimicking sarcopenia, Olg combined with BCAA supplementation enhanced mTOR/p70S6K activity more than BCAA alone. However, blocked LAT1 by JPH203 reversed the synergistic effect of the combination of Olg and BCAAs. Taken together, changes in LAT1 and BCAT2 during aging profoundly alter BCAA availability and nutrient signaling in aged mice. Olg increases BCAA-stimulated protein synthesis via modulating BCAA transportation and BCAA catabolism. Combining Olg and BCAAs may be a useful nutritional strategy for alleviating sarcopenia. [ABSTRACT FROM AUTHOR]

Major Depressive Disorder (MDD) is a prevalent mental health condition with a complex pathophysiology involving neuroinflammation, neurodegeneration, and disruptions in neuronal and glial cell function. Microglia, the innate immune cells of the central nervous system, release inflammatory cytokines in response to pathological changes associated with MDD. Damage-associated molecular patterns (DAMPs) act as alarms, triggering microglial activation and subsequent inflammatory cytokine release. This review examines the cellular mechanisms underlying MDD pathophysiology, focusing on the lipid-mediated modulation of neuroinflammation. We explore the intricate roles of microglia and astrocytes in propagating inflammatory cascades and discuss how these processes affect neuronal integrity at the cellular level. Central to our analysis are three key molecules: High Mobility Group Box 1 (HMGB1) and S100 Calcium Binding Protein β (S100β) as alarmins, and Neuron-Specific Enolase (NSE) as an indicator of neuronal stress. We present evidence from in vitro and ex vivo studies demonstrating how these molecules reflect and contribute to the neuroinflammatory milieu characteristic of MDD. The review then explores the potential of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) as neuroinflammation modulators, examining their effects on microglial activation, cytokine production, and neuronal resilience in cellular models of depression. We critically analyze experimental data on how ω-3 PUFA supplementation influences the expression and release of HMGB1, S100β, and NSE in neuronal and glial cultures. By integrating findings from lipidomic and cellular neurobiology, this review aims to elucidate the mechanisms by which ω-3 PUFAs may exert their antidepressant effects through modulation of neuroinflammatory markers. These insights contribute to our understanding of lipid-mediated neuroprotection in MDD and may inform the development of targeted, lipid-based therapies for both depression and neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Catheter ablation for tachyarrhythmia via superior approach has been used in patients without possible inferior vena cava access such as in cases of venous occlusion or complex anomaly. Difficulty in catheter manipulation, instability, number of required vascular access, and radiation exposure of operator had been described in the procedure. Application of three‐dimensional (3‐D) mapping system in catheter ablation via superior approach could navigate the guiding catheter and provide more precise ablation. We reported four cases receiving catheter ablation due to atrioventricular nodal reentry tachycardia, atrial fibrillation, and right ventricular arrhythmia via superior approach facilitated by 3‐D mapping system with fewer vascular access and catheters. [ABSTRACT FROM AUTHOR]

Janus metasurfaces, offering versatile light manipulation contingent on incident direction, are explored across microwave to mid‐infrared spectra. Nonetheless, prior designs often resort to spatial multiplexing or vertical stacking, entailing complex fabrication. Metallic Janus metasurfaces, owing to material properties, suffer notable Ohmic losses in the visible spectrum. In this study, Single‐layer TiO2‐based Janus metasurfaces with arbitrary polarization control is experimentally demonstrated, exhibiting directionally asymmetric functionalities in spin and orbital angular momentum (OAM). A novel Jones matrix formulation tailored for Janus metasurfaces is presented, enabling efficient generation of two asymmetric, high‐purity OAM states of vortex beams at wavelength of 532 nm, contingent on incidence direction. This innovation facilitates compact and versatile phase manipulation, encompassing applications such as lasers and optical combiners, thereby expanding its utility across diverse domains. [ABSTRACT FROM AUTHOR]

Introduction: Comprehensive next-generation sequencing (NGS) of non-small-cell lung cancer specimens can identify oncogenic driver mutations and their corresponding targeted therapies. Plasma cell-free DNA (cfDNA) genotyping is easy to perform; however, false negatives cannot be overlooked. We explored malignant pleural effusion (MPE), a rich source of cfDNA, as a non-inferior alternative to tumor tissues for genotyping. Methods: We conducted a prospective trial including 39 patients with newly diagnosed stage IV lung adenocarcinoma who presented with MPE. Tissue tests matching hotspot variants, including EGFR, ALK, and ROS1, were compared with the AlphaLiquid100 of PE-cfDNA. Results: Among the 39 PE-cfDNA samples successfully sequenced, 32 (82.1%) had a PE cell-block tumor content of < 10%. Standard tissue or cell-block testing for EGFR, ALK, and ROS1 identified 20 mutations (51.3%), whereas PE cfDNA identified 25 mutations (64.1%). Five EGFR mutations were observed in PE cfDNA but not in Cobas EGFR owing to coverage or insufficient tumor content issues. The overall rate of oncogenic mutations identified in the PE cfDNA was 92.3%, and the mutation distribution was as follows: even with a very low cfDNA input, high detection rates could be achieved. Otherwise, most patients harbored co-mutations. Comparison of pleural fluid NGS with traditional testing revealed differences in accuracy. We also followed up with patients with EGFR-sensitizing mutations who had a treatment response rate of 97.2% after 3 months. Conclusions: Genotyping of MPE supernatant cfDNA is feasible in clinical practice, in addition to plasma and tumor testing, to improve diagnostic yield and extend patients' benefit from targeted therapies. [ABSTRACT FROM AUTHOR]

The SARS‐CoV‐2 main protease (Mpro) is an essential enzyme that promotes viral transcription and replication. Mpro conserved nature in different variants and its nonoverlapping nature with human proteases make it an attractive target for therapeutic intervention against SARS‐CoV‐2. In this work, the interaction mechanism between Mpro and diindolylmethane derivatives was investigated by molecular docking, enzymatic inhibition assay, UV–vis, fluorescence spectroscopy, and circular dichroism spectroscopy. Results of IC50 values show that 1p (9.87 μM) was the strongest inhibitor for Mpro in this work, which significantly inhibited the activity of Mpro. The binding constant (4.07 × 105 Lmol−1), the quenching constant (5.41 × 105 Lmol−1), and thermodynamic parameters indicated that the quenching mode of 1p was static quenching, and the main driving forces between 1p and Mpro are hydrogen bond and van der Waals force. The influence of molecular structure on the binding is investigated. Chlorine atoms and methoxy groups are favorable for the diindolylmethane derivative inhibitors of Mpro. This work confirms the changes in the microenvironment of Mpro by 1p, and provides clues for the design of potential inhibitors. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusions The objective of this study is to investigate the effect of collagen matrix with polydeoxyribonucleotide (PDRN) at two concentrations on keratinized tissue (KT) regeneration for buccally positioned implants in canines.Four implants were placed in the edentulous mandible of five dogs simultaneously with KT removal. The implants were positioned buccally with respect to the ridge crest. After 2 months, KT augmentation was performed applying the following treatment modalities:(1) free gingival graft (FGG), (2) xenogeneic collagen matrix (XCM), (3) XCM loaded with 2 mg/mL PDRN (PDRN2), and (4) XCM loaded with 4 mg/mL PDRN (PDRN4). All animals were sacrificed 3 months later. Outcomes included clinical (KT height) and histomorphometric measurements (KT height/length, level of the mucosa, mucosal thickness, supracrestal soft tissue height).Clinical and histomorphometric KT formation at 3 months was greatest in groups with FGG (4.70 ± 1.00/3.94 ± 0.93 mm) and PDRN2 (4.85 ± 1.43/3.95 ± 0.87 mm). Group PDRN2 (1.87 ± 1.50 mm) showed a higher marginal mucosal level with respect to the implant platform compared to other groups (range: 0.57 ± 0.97–0.69 ± 1.14 mm). All groups presented a soft tissue thickness of < 2 mm on the buccal aspect of the implants.Based on the limitations of this pilot preclinical study, XCM with 2 mg/mL of PDRN demonstrated a potential for KT augmentation. [ABSTRACT FROM AUTHOR]

Background: Normal cells express functional tumor suppressor WW domain-containing oxidoreductase (WWOX), designated WWOXf. UV irradiation induces WWOXf cells to undergo bubbling cell death (BCD) — an event due to the accumulation of nuclear nitric oxide (NO) gas that forcefully pushes the nuclear and cell membranes to form one or two bubbles at room temperature (22 °C) and below. In contrast, when WWOX-deficient or -dysfunctional (WWOXd) cells are exposed to UV and/or cold shock, the cells undergo nuclear pop-out explosion death (POD). We aimed to determine the morphological and biochemical changes in WWOXf cells during BCD versus apoptosis. Methods: WWOXf and WWOXd cells were exposed to UV followed by measuring BCD or POD by time-lapse microscopy and/or time-lapse holographic microscopy at 4, 22, or 37 °C to visualize morphological changes. Live cell stains were used to measure the kinetics of nitric oxide (NO) production and Ca2+ influx. Extent of cell death was measured by uptake of propidium iodide and by internucleosomal DNA fragmentation using agarose gel electrophoresis. Results: WWOXf cells were exposed to UV and then cold shock, or cold shock and then UV, and cultured at 4, 10, and 22 °C, respectively. Initially, UV induced calcium influx and NO production, which led to nuclear bubbling and final death. Cold shock pretreatment completely suppressed UV-mediated bubbling at 37 °C, so the UV/cold shock-treated cells underwent apoptosis. Without cold shock, UV only induced bubbling at all temperatures, whereas the efficiency of bubbling at 37 °C was reduced by greater than 50%. Morphologically, the WWOXf cell height or thickness was significantly increased during cell division or apoptosis, but the event did not occur in BCD. In comparison, when WWOXd cancer cells received UV or UV/cold shock, these cells underwent NO-independent POD. UV/cold shock effectively downregulated the expression of many proteins such as the housekeeping α-tubulin (> 70%) and β-actin (< 50%), and cortactin (> 70%) in WWOXf COS7 cells. UV/cold shock induced relocation of α-tubulin to the nucleus and nuclear bubbles in damaged cells. UV induced co-translocation of the WWOX/TRAF2 complex to the nuclei, in which the prosurvival TRAF2 blocked the proapoptotic WWOX via its zinc finger domain. Without WWOX, TRAF2 did not relocate to the nuclei. Cold shock caused the dissociation of the WWOX/TRAF2 complex in the nucleus needed for BCD. In contrast, the formation of the WWOX/TRAF2 complex, plus p53, was strengthened at 37 °C required for apoptosis. Conclusions: The temperature-sensitive nuclear WWOX/TRAF2 complex acts as a molecular switch, whose dissociation favors BCD at low temperatures, and the association supports apoptosis at 37 °C in UV-treated WWOXf cells. [ABSTRACT FROM AUTHOR]

This study proposed an improved full-scale aggregated MobileUNet (FA-MobileUNet) model to achieve more complete detection results of oil spill areas using synthetic aperture radar (SAR) images. The convolutional block attention module (CBAM) in the FA-MobileUNet was modified based on morphological concepts. By introducing the morphological attention module (MAM), the improved FA-MobileUNet model can reduce the fragments and holes in the detection results, providing complete oil spill areas which were more suitable for describing the location and scope of oil pollution incidents. In addition, to overcome the inherent category imbalance of the dataset, label smoothing was applied in model training to reduce the model's overconfidence in majority class samples while improving the model's generalization ability. The detection performance of the improved FA-MobileUNet model reached an mIoU (mean intersection over union) of 84.55%, which was 17.15% higher than that of the original U-Net model. The effectiveness of the proposed model was then verified using the oil pollution incidents that significantly impacted Taiwan's marine environment. Experimental results showed that the extent of the detected oil spill was consistent with the oil pollution area recorded in the incident reports. [ABSTRACT FROM AUTHOR]

Our previous study has found that monoclonal antibodies targeting a conserved epitope peptide spanning from residues 1144 to 1156 of SARS-CoV-2 spike (S) protein, namely S(1144–1156), can broadly neutralize all of the prevalent SARS-CoV-2 strains, including the wild type, Alpha, Epsilon, Delta, and Gamma variants. In the study, S(1144–1156) was conjugated with bovine serum albumin (BSA) and formulated with Montanide ISA 51 adjuvant for inoculation in BALB/c mice to study its potential as a vaccine candidate. Results showed that the titers of S protein-specific IgGs and the neutralizing antibodies in mouse sera against various SARS-CoV-2 variants, including the Omicron sublineages, were largely induced along with three doses of immunization. The significant release of IFN-γ and IL-2 was also observed by ELISpot assays through stimulating vaccinated mouse splenocytes with the S(1144–1156) peptide. Furthermore, the vaccination of the S(1143–1157)- and S(1142–1158)-EGFP fusion proteins can elicit more SARS-CoV-2 neutralizing antibodies in mouse sera than the S(1144–1156)-EGFP fusion protein. Interestingly, the antisera collected from mice inoculated with the S(1144–1156) peptide vaccine exhibited better efficacy for neutralizing Omicron BA.2.86 and JN.1 subvariants than Omicron BA.1, BA.2, and XBB subvariants. Since the amino acid sequences of the S(1144–1156) are highly conserved among various SARS-CoV-2 variants, the immunogen containing the S(1144–1156) core epitope can be designed as a broadly effective COVID-19 vaccine. Key points: • Inoculation of mice with the S(1144–1156) peptide vaccine can induce bnAbs against various SARS-CoV-2 variants. • The S(1144–1156) peptide stimulated significant release of IFN-γ and IL-2 in vaccinated mouse splenocytes. • The S(1143–1157) and S(1142–1158) peptide vaccines can elicit more SARS-CoV-2 nAbs in mice. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) have a high incidence of dyslipidemia comprising high triglyceride (TG) and low high-density lipoprotein (HDL)-cholesterol levels. An abnormal increase of TGs within cells can lead to intracellular lipid accumulation. In addition to dyslipidemia, hyperglycemia in diabetes may elicit ectopic lipid deposition in non-adipose tissues. Hyperglycemia increases intracellular levels of methylglyoxal (MG) leading to cellular dysfunction. A deficit of glyoxalase I (GLO1) contributes to dicarbonyl stress. Whether dicarbonyl stress induced by MG causes renal lipotoxicity through alteration of lipid metabolism signaling is still unknown. In this study, mice with high fat diet-induced diabetes were used to investigate the renal pathology induced by MG. NRK52E cells treated with MG were further used in vitro to delineate the involvement of lipogenic signaling. After treatment with MG for 12 weeks, plasma TG levels, renal fatty changes, and tubular injuries were aggravated in diabetic mice. In NRK52E cells, MG activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and sterol regulatory element-binding protein 1 (SREBP1), resulting in stimulation of fatty acid synthase. The intracellular accumulation of lipid droplets was mainly contributed by TGs, which increased the oxidative stress accompanied by high Nrf2 expression. In addition, MG time-dependently activated cyclin D, cyclin-dependent kinase 4 (CDK4), and cleaved caspase-3, evidencing that G0/G1 arrest was associated with apoptosis of NRK52E cells. In conclusion, our studies revealed the mechanism of lipotoxicity caused by MG. The target of such dicarbonyl stress may become a promising therapy for diabetic CKD. [ABSTRACT FROM AUTHOR]

Background: The direct anterior approach (DAA) for total hip arthroplasty (THA) has gained popularity due to perceived advantages in achieving better early outcomes. However, the theoretical benefits such as precise implant positioning and accurate leg length restoration are still inconsistent. In this study, we compared implant position and leg length discrepancy (LLD) of the DAA and posterolateral approach (PLA) conducted by a single surgeon who had mastered both approaches. Methods: This study retrospectively reviewed the medical records and radiographic images of 244 patients who underwent THA between 2012 and 2021 by a single experienced surgeon using either the DAA (n = 120) or PLA (n = 124). Postoperative pelvic anteroposterior radiographs at 6 months follow-up were used to assess acetabular component inclination and anteversion, as well as LLD. Mann-Whitney U tests and Chi-squared test were performed to compare outcomes between the two approaches. Results: No significant differences were observed in patient demographics between the two groups. The DAA group demonstrated significantly lower postoperative LLD (0.00 mm) compared to the PLA group (5.00 mm, p < 0.0001). No significant difference was observed in the Lewinnek zone for cup anteversion and inclination angles between the two groups. Conclusions: For experienced surgeons in other approaches, our findings suggest transferring to the DAA may not substantially improve cup positioning, but it might slightly enhance limb length measurement. For surgeons already proficient in other approaches and deciding to maintain those approaches, their primary concern for optimal THA outcome should be striving for leg length equivalence. [ABSTRACT FROM AUTHOR]

Background: Bone grafts are extensively used for repairing bone defects and voids in orthopedics and dentistry. Moldable bone grafts offer a promising solution for treating irregular bone defects, which are often difficult to fill with traditional rigid grafts. However, practical applications have been limited by insufficient mechanical strength and rapid degradation. Methods: This study developed a ceramic composite bone graft composed of calcium sulfate (CS), β-tricalcium phosphate (β-TCP) with/without graphene oxide (GO) nano-particles. The biomechanical properties, degradation rate, and in-vitro cellular responses were investigated. In addition, the graft was implanted in-vivo in a critical-sized calvarial defect model. Results: The results showed that the compressive strength significantly improved by 135% and the degradation rate slowed by 25.5% in comparison to the control model. The addition of GO nanoparticles also improved cell compatibility and promoted osteogenic differentiation in the in-vitro cell culture study and was found to be effective at promoting bone repair in the in-vivo animal model. Conclusions: The mixed ceramic composites presented in this study can be considered as a promising alternative for bone graft applications. [ABSTRACT FROM AUTHOR]

Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of unknown etiology that commonly affects adolescents, imposing significant socioeconomic burdens. Effective management necessitates a comprehensive approach that takes into account multiple factors, including growth potential and psychological issues. Despite significant advancements in AIS management, several questions regarding optimal treatment strategies persist. Recent technological advancements are transforming the treatment landscape, encompassing advancements in bracing, robotic-assisted deformity corrections, and other interventions. This review explores current issues debated in the literature concerning the treatment of AIS, focusing on contemporary high-level evidence (e.g., meta-analyses and randomized controlled trials). Furthermore, this review explores cutting-edge developments and future directions in AIS management, including the integration of artificial intelligence and augmented reality. [ABSTRACT FROM AUTHOR]

Artificial intelligence has garnered significant attention in recent years as a rapidly advancing field of computer technology. With the continual advancement of computer hardware, deep learning has made breakthrough developments within the realm of artificial intelligence. Over the past few years, applying deep learning architecture in medicine and industrial anomaly inspection has significantly contributed to solving numerous challenges related to efficiency and accuracy. For excellent results in radiological, pathological, endoscopic, ultrasonic, and biochemical examinations, this paper utilizes deep learning combined with image processing to identify spinal canal and vertebral foramen dimensions. In existing research, technologies such as corrosion and expansion in magnetic resonance image (MRI) processing have also strengthened the accuracy of results. Indicators such as area and Intersection over Union (IoU) are also provided for assessment. Among them, the mean Average Precision (mAP) for identifying intervertebral foramen (IVF) and intervertebral disc (IVD) through YOLOv4 is 95.6%. Resnet50 mixing U-Net was employed to identify the spinal canal and intervertebral foramen and achieved IoU scores of 79.11% and 80.89%. [ABSTRACT FROM AUTHOR]

Simple Summary: Mouse models of disease are commonly used to generate compelling data which are the basis for biological conviction in drug discovery. Systemic lupus erythematosus (SLE) is a debilitating autoimmune disease which can often lead to kidney failure, and there are many mouse models that claim to mimic the disease, but none can completely reproduce all aspects of human SLE. To effectively utilize these models for drug development, we must understand which biological similarities they share with human SLE patients. Here, we compared a select number of lupus mouse models to see how well immune pathways in kidney samples mimic human disease in kidney samples from lupus patients. The mouse models vary in the type and intensity of immune responses that were observed. Each mouse model shares various aspects of immune response with human SLE patients and should be utilized based on drug targets and shared biological pathways. Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease which can present with mixed organ involvement. Kidney involvement in lupus nephritis (LN) is a severe complication and major cause of mortality in SLE patients, second only to cardiovascular disease. While mouse models have helped uncover some molecular pathways involved in SLE/LN, we need a better understanding of the connection of these pathways and the immune cells involved in disease pathogenesis to develop new and effective therapies. Furthermore, models used for studying SLE/LN in mice have a heterogeneous immune response and may not always represent disease manifestations observed in patients. Identifying models that have shared pathways with human disease would allow for better translation for developing effective SLE/LN therapies. The molecular pathways of five different SLE/LN models (MRL/lpr, poly (I:C)-induced, interferon-α-induced, bm12 GvHD, and spontaneous NZB/W F1) were compared to characterize the immune response in mouse kidneys. These models demonstrated varied magnitudes in immune responses and proportions of innate vs. adaptive cell involvement. These findings were compared to human molecular pathways and cell types from public databases, including the Accelerating Medicine Partnership–Systemic Lupus Erythematosus Program (AMP-SLE), to help corelate mechanisms involved in mouse models to human disease. [ABSTRACT FROM AUTHOR]

Prosocial behavior is fundamental for healthcare students, shaped by their traits and the external environment. Online information seeking is the most commonly used way for healthcare students to access pandemics; however, it is unclear whether the willingness of healthcare students to help others will be affected by pandemic information via the Internet environment. The current study takes the COVID-19 pandemic as an example, investigating how 81 healthcare students with varying prosocial tendencies behaved helpfully after being exposed to pandemic-related pictures online. Study 1 measured the influence of emotional contagion (positive emotion/negative emotion) from online information on students' prosocial behavior; Study 2 examined online information's influence on prosocial behavior by controlling individuals' epistemic motivation (goal-directed task/no-goal-directed task) to gain pandemic information. The results indicated that negative pandemic information was more likely to influence students with low prosocial tendencies, which would then lead to a decrease in prosocial actions (F = 7.842, p = 0.005). Further, students with low prosocial tendencies were more likely to engage in prosocial behavior when they did not aim goal-directed attention to the pandemic-related information, compared to those with goal-directed attention (F = 9.159, p = 0.003). Participants with high prosocial tendencies did not differ much in helping others (p > 0.05). The results indicated that only healthcare students with limited prosocial tendencies were less inclined to assist others after receiving negative information about the pandemic. Thus, reducing their deliberate approach to online information related to the pandemic will increase their chances of taking prosocial behavior. [ABSTRACT FROM AUTHOR]

Low back pain is a common clinical symptom of intervertebral disc degeneration (IVDD), which seriously affects the quality of life of the patients. The abnormal apoptosis and senescence of nucleus pulposus cells (NPCs) play important roles in the pathogenesis of IVDD. PHLDA2 is an imprinted gene related to cell apoptosis and tumour progression. However, its role in NPC degeneration is not yet clear. Therefore, this study was set to explore the effects of PHLDA2 on NPC senescence and apoptosis and the underlying mechanisms. The expression of PHLDA2 was examined in human nucleus pulposus (NP) tissues and NPCs. Immunohistochemical staining, magnetic resonance imaging imaging and western blot were performed to evaluate the phenotypes of intervertebral discs. Senescence and apoptosis of NPCs were assessed by SA‐β‐galactosidase, flow cytometry and western blot. Mitochondrial function was investigated by JC‐1 staining and transmission electron microscopy. It was found that the expression level of PHLDA2 was abnormally elevated in degenerated human NP tissues and NPCs. Furthermore, knockdown of PHLDA2 can significantly inhibit senescence and apoptosis of NPCs, whereas overexpression of PHLDA2 can reverse senescence and apoptosis of NPCs in vitro. In vivo experiment further confirmed that PHLDA2 knockdown could alleviate IVDD in rats. Knockdown of PHLDA2 could also reverse senescence and apoptosis in IL‐1β‐treated NPCs. JC‐1 staining indicated PHLDA2's knockdown impaired disruption of the mitochondrial membrane potential and also ameliorated superstructural destruction of NPCs as showed by transmission electron microscopy. Finally, we found the PHLDA2 knockdown promoted Collagen‐II expression and suppressed MMP3 expression in NPCs by repressing wnt/β‐catenin pathway. In conclusion, the results of the present study showed that PHLDA2 promotes IL‐1β‐induced apoptosis and senescence of NP cells via mitochondrial route by activating the Wnt/β‐catenin pathway, and suggested that therapy targeting PHLDA2 may provide valuable insights into possible IVDD therapies. [ABSTRACT FROM AUTHOR]

Gut microbiota dysbiosis has been implicated in rheumatoid arthritis (RA) and influences disease progression. Although molecular and culture‐independent studies revealed RA patients harbored a core microbiome and had characteristic bacterial species, the lack of cultured bacterial strains had limited investigations on their functions. This study aimed to establish an RA‐originated gut microbial biobank (RAGMB) that covers and further to correlates and validates core microbial species on clinically used and diagnostic inflammation and immune indices. We obtained 3200 bacterial isolates from fecal samples of 20 RA patients with seven improved and 11 traditional bacterial cultivation methods. These isolates were phylogenetically identified and selected for RAGMB. The RAGMB harbored 601 bacterial strains that represented 280 species (including 43 novel species) of seven bacterial phyla. The RAGMB covered 93.2% at species level of medium‐ and high‐abundant (relative abundances ≥0.2%) RA gut microbes, and included four rare species of the phylum Synergistota. The RA core gut microbiome was defined and composed of 20 bacterial species. Among these, Mediterraneibacter tenuis and Eubacterium rectale were two species that statistically and significantly correlated with clinically used diagnostic indices such as erythrocyte sedimentation rate (ESR) and IL‐10. Thus, M. tenuis and E. rectale were selected for experimental validation using DSS‐treated and not DSS‐treated mice model. Results demonstrated both M. tenuis and E. rectale exacerbated host inflammatory responses, including shortened colon length and increased spleen weight, decreased IL‐10 and increased IL‐17A levels in plasma. Overall, we established the RAGMB, defined the RA core microbiome, correlated and demonstrated core microbial species effected on host inflammatory and immune responses. This work provides diverse gut microbial resources for future studies on RA etiology and potential new targets for new biomedical practices. Highlights: An rheumatoid arthritis (RA)‐originated gut microbial biobank (RAGMB) was established, comprising 601 bacterial strains representing 280 species (including 43 novel species) across seven bacterial phyla.RAGMB covers 93.2% of medium‐ and high‐abundant RA gut microbe species from isolated samples.The RA core microbiome consists of 20 bacterial species, with Mediterraneibacter tenuis and Eubacterium rectale showing significant correlations with clinical indices such as ESR and IL‐10.RA core species Mediterraneibacter tenuis and Eubacterium rectale exacerbate inflammatory responses, including shortened colon length, enlarged spleen and altered plasma cytokine levels. [ABSTRACT FROM AUTHOR]

Papillary thyroid cancer (PTC) is one of the most treatable forms of cancer, with many cases being fully curable. However, resistance to anticancer drugs often leads to metastasis or recurrence, contributing to the failure of cancer therapy and, ultimately, patient mortality. The mechanisms underlying molecular differences in patients with metastatic or recurrent PTC, particularly those resistant to anticancer drugs through epigenetic reprogramming, remain poorly understood. Consequently, refractory PTC presents a critical challenge, and effective therapeutic strategies are urgently needed. Therefore, this study aimed to identify small-molecule inhibitors to enhance treatment efficacy in lenvatinib-resistant PTC. We observed an increase in sarco/endoplasmic reticulum calcium ATPase (SERCA) levels in patient-derived lenvatinib-resistant PTC cells compared with lenvatinib-sensitive ones, highlighting its potential as a therapeutic target. We subsequently identified two SERCA inhibitors [candidates 40 (isoflurane) and 42 (ethacrynic acid)] through in silico screening. These candidates demonstrated significant tumor shrinkage in a xenograft tumor model and reduced cell viability in patient-derived lenvatinib-resistant PTC cells when used in combination with lenvatinib. Our findings have potential clinical value for the development of new combination therapies to effectively target highly malignant, anticancer drug-resistant cancers. [ABSTRACT FROM AUTHOR]

Pasteurella spp. can cause fatal zoonotic infections in humans. We performed a multicenter study to investigate the prevalence and clinical features of Pasteurella infections in South Korea during 2018‒2022. We also conducted a collaborative systematic review and metaanalysis of the global burden of Pasteurella bacteremia. The study included 283 cases and found an increasing trend in Pasteurella infections. Blood cultures were positive in 8/35 (22.9%) cases sampled, for an overall bacteremia-associated rate of 2.8% (8/283). Aging was a significant risk factor for bacteremia (odds ratio 1.05 [95% CI 1.01–1.10]), according to multivariate analyses. For the meta-analysis, we included a total of 2,012 cases from 10 studies. The pooled prevalence of bacteremia was 12.4% (95% CI 7.3%–18.6%) and of mortality 8.4% (95% CI 2.7%–16.5%). Our findings reflect the need for greater understanding of the increase in Pasteurella infections and the global burden of Pasteurella bacteremia to determine appropriate case management. [ABSTRACT FROM AUTHOR]

This article discusses the use of a non-invasive scanning technique called cellular resolution full-field optical coherence tomography (CRFF-OCT) to analyze the features of melasma, a skin condition associated with photoaging. The study found that melasma lesions had significantly higher numbers and activities of activated melanocytes, resulting in spinous hyperpigmentation and increased vascularity compared to nearby perilesions. However, there were no significant differences in basal hyperpigmentation, basement membrane disruption, melanophages, inflammatory cells, or collagen degradation between the two. The findings suggest that photodamage is present in the facial skin of patients with melasma, and treatment should focus on rejuvenating the entire dermis. [Extracted from the article]

With the increasing popularity of watching baseball videos, there is a growing desire among fans to enjoy the highlights of these videos. However, the extraction of the highlights from lengthy baseball videos faces a significant challenge due to its time-consuming and labor-intensive nature. To address this challenge, this paper proposes a novel mechanism, called Hierarchical Multimodal Transformer for Video query (HMTV). The proposed HMTV incorporates a two-phase involving Coarse-Grained clipping for candidate videos and Fine-Grained identification for highlights. In the Coarse-Grained phase, a pitching detection model is employed to extract relevant candidate videos from baseball videos, encompassing the features of pitch deliveries and pitching. In the Fine-Grained phase, Transformer encoder and pre-trained Bidirectional Encoder Representations from Transformers (BERT) are utilized to capture relationship features between frames of candidate videos and words from users’ questions, respectively. These relationship features are then fed into the Video Query (VideoQ) model, implemented by the Text Video Attention (TVA). The VideoQ model identifies the start and end positions of the highlights mentioned in the query within the candidate videos. Simulation results demonstrate that the proposed HMTV significantly improves accuracy of highlights identification in terms of precision, recall, and F1-score. [ABSTRACT FROM AUTHOR]

With the increasing popularity of watching baseball videos, there is a growing desire among fans to enjoy the highlights of these videos. However, the extraction of the highlights from lengthy baseball videos faces a significant challenge due to its time-consuming and labor-intensive nature. To address this challenge, this paper proposes a novel mechanism, called Hierarchical Multimodal Transformer for Video query (HMTV). The proposed HMTV incorporates a two-phase involving Coarse-Grained clipping for candidate videos and Fine-Grained identification for highlights. In the Coarse-Grained phase, a pitching detection model is employed to extract relevant candidate videos from baseball videos, encompassing the features of pitch deliveries and pitching. In the Fine-Grained phase, Transformer encoder and pre-trained Bidirectional Encoder Representations from Transformers (BERT) are utilized to capture relationship features between frames of candidate videos and words from users’ questions, respectively. These relationship features are then fed into the Video Query (VideoQ) model, implemented by the Text Video Attention (TVA). The VideoQ model identifies the start and end positions of the highlights mentioned in the query within the candidate videos. Simulation results demonstrate that the proposed HMTV significantly improves accuracy of highlights identification in terms of precision, recall, and F1-score. [ABSTRACT FROM AUTHOR]

The food industry is still dependent on plastics for packaging materials, primarily due to their effectiveness in safeguarding products from external factors, such as moisture, light, and gas. However, traditional plastic packaging lacks the ability to actively preserve the quality and extend the shelf life of food. To address this challenge, various methods are currently being developed through surface modifications and the incorporation of active compounds. In most cases, studies on the modification of active film using low-pressure plasma (LPP) use different parameters, including time, pressure, and power, without a systematic optimization process. Therefore, this study aims to determine the optimum parameters for the combination of LPP treatment and Pickering emulsion (PE) of nutmeg essential oil (NEO) using Taguchi's orthogonal assay design (OAD) to produce LDPE-active film. The results showed that the optimum conditions were 15 W LPP power, 30 s LPP duration time, and 1.5% PE-NEO concentration. These results showed a 50% improvement in power and time efficiency. LDPE film–loaded PE-NEO was then applied to tilapia fillets in cold storage. The results showed that the TBARS and TBVN values of the samples after the treatment were lower than those of the control by 12.11% and 16.74%, respectively. [ABSTRACT FROM AUTHOR]

Hyperglycemia in type 2 diabetes leads to diabetic peripheral neuropathy (DPN) and neuropathic pain, yet the association between glycemic variability and painful DPN remains insufficiently evidenced. To address this, we conducted a prospective longitudinal cohort study involving adult type 2 diabetes patients at a medical center. DPN was identified using the Michigan Neuropathy Screening Instrument (MNSI), and neuropathic pain was assessed with the Taiwan version of the Douleur Neuropathique 4 (DN4-T) questionnaire. At baseline in 2013, all participants were free of DPN and were re-evaluated in 2019 for the development of painful DPN. We measured visit-to-visit glycemic fluctuations using the coefficient of variation (CV) of fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c). Patients were stratified into tertiles according to their FPG-CV and HbA1c-CV. Among the 622 participants, 267 developed DPN during the six-year follow-up. Following matching of age and sex, 210 patients without DPN and 210 with DPN (including 26 with neuropathic pain) were identified. Our findings revealed a significant association between high FPG-CV and painful DPN, with the highest tertile showing an adjusted odds ratio of 2.82 (95% confidence interval 1.04–7.64) compared to the lowest tertile. On the contrary, HbA1c-CV did not show a significant association with the risk of painful DPN. Our study indicates that higher FPG-CV is associated with an increased risk of painful DPN, supporting the role of glycemic variability in the development of painful DPN. [ABSTRACT FROM AUTHOR]

The development of efficient methodologies for the controlled manufacture of specific stereoisomers bearing quaternary stereocenters has prompted advances in a variety of scientific disciplines including pharmaceutical chemistry, materials science, and chemical biology. However, complete control of the absolute and relative stereochemical configurations of alkyne derivatives remains an unmet synthetic challenge. Herein, a Ni/Cu dual‐catalyzed asymmetric propargylic substitution reaction is presented to produce propargylated products with all‐carbon quaternary stereocenters in high yields with significant diastereo‐ and enantioselectivities (up to >20:1 dr, >99% ee). The synthesis of all stereochemical variants of methohexital, a widely used sedative‐hypnotic drug, exemplifies the efficacy of dual‐catalyzed stereodivergent propargylation. [ABSTRACT FROM AUTHOR]

Background/Objectives: Geriatric hip fracture patients have an increased risk of malnutrition. Proper nutritional supply in the perioperative period is very important for their recovery. Oral nutritional supplements (ONSs) are recommended in geriatric hip fracture patients to improve dietary intake and prevent complications. This study aimed to evaluate the efficacy of postoperative ONSs after total hip arthroplasty in geriatric hip fracture patients. Methods: A retrospective study of elderly patients who underwent total hip arthroplasty for hip fracture was conducted. Data from patients who received ONSs postoperatively until hospital discharge (ONS group, n = 69) were compared with patients who did not receive ONSs (control group, n = 168). Laboratory test results, including serum protein and albumin levels, length of hospital stay, and the incidence of postoperative medical complications of the two groups, were analyzed. Results: Preoperative serum protein and albumin levels were significantly higher in the control group (p = 0.002 and p = 0.010, respectively). However, the degree of decline for both protein and albumin levels was significantly less in the ONS group (p < 0.001 for both). Serum albumin levels were significantly higher in the ONS group at postoperative two-week follow-up (p = 0.006). The length of hospital stay was shorter in the ONS group (p < 0.001). The incidence of postoperative delirium was significantly higher in the control group (p = 0.007). Conclusions: In geriatric hip fracture patients, postoperative ONSs can improve postoperative nutritional status, shorten the length of hospital stay, and reduce the incidence of postoperative delirium. [ABSTRACT FROM AUTHOR]