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In this paper, we investigate the existence and uniqueness of the S-asymptotically ω -periodic mild solutions to a class of multi-term time-fractional measure differential equations with nonlocal conditions in an ordered Banach spaces. Firstly, we look for suitable concept of S-asymptotically ω -periodic mild solution to our concern problem, by means of Laplace transform and (β , γ k) -resolvent family { S β , γ k (t) } t ≥ 0 . Secondly, we construct monotone iterative method in the presence of the lower and upper solutions to the delayed fractional measure differential equations, and obtain the existence of maximal and minimal S-asymptotically ω -periodic mild solutions for the mentioned system. Finally, as the application of abstract results, an example is given to illustrate our main results. [ABSTRACT FROM AUTHOR]

An increased risk of target organ damage (TOD) has been reported in patients with primary aldosteronism (PA). However, there is relatively little related research on the correlation between the degree of TOD and those with and without PA in newly diagnosed hypertensive patients. The aim of this study was to assess the association between PA and TOD among patients with newly diagnosed hypertension. Newly diagnosed hypertensive patients were consecutively recruited from January 2015 to June 2020 at the University of Hong Kong‐Shenzhen Hospital. Patients were stratified into those with and without PA. Data for left ventricular mass index (LVMI), carotid intima‐media thickness (CIMT) and plaque, and microalbuminuria were systematically collected. A total of 1044 patients with newly diagnosed hypertension were recruited, 57 (5.5%) of whom were diagnosed with PA. Patients with PA had lower blood pressure, serum lipids, body mass index, and plasma renin activity and a higher incidence of hypokalemia than those without PA. In contrast, the prevalence of left ventricular hypertrophy, increased CIMT, and microalbuminuria was higher in patients with PA than in those without PA. Multivariable regression analysis demonstrated that PA was independently associated with increased LVMI, CIMT and microalbuminuria. Among patients with newly diagnosed hypertension, those with PA had more severe TOD, including a higher LVMI, CIMT and microalbuminuria, than those without PA. These findings emphasize the need for screening TOD in newly diagnosed hypertension due to underlying PA. [ABSTRACT FROM AUTHOR]

Background: Leptomeningeal metastasis (LM) of small cell lung cancer (SCLC) is a highly detrimental occurrence associated with severe neurological disorders, lacking effective treatment currently. Proteolysis-targeting chimeric molecules (PROTACs) may provide new therapeutic avenues for treatment of podophyllotoxin derivatives-resistant SCLC with LM, warranting further exploration. Methods: The SCLC cell line H128 expressing luciferase were mutated by MNNG to generate H128-Mut cell line. After subcutaneous inoculation of H128-Mut into nude mice, H128-LM and H128-BPM (brain parenchymal metastasis) cell lines were primarily cultured from LM and BPM tissues individually, and employed to in vitro drug testing. The SCLC-LM mouse model was established by inoculating H128-LM into nude mice via carotid artery and subjected to in vivo drug testing. RNA-seq and immunoblotting were conducted to uncover the molecular targets for LM. Results: The SCLC-LM mouse model was successfully established, confirmed by in vivo live imaging and histological examination. The upregulated genes included EZH2, SLC44A4, VEGFA, etc. in both BPM and LM cells, while SLC44A4 was particularly upregulated in LM cells. When combined with PROTAC EZH2 degrader-1, the drug sensitivity of cisplatin, etoposide (VP16), and teniposide (VM26) for H128-LM was significantly increased in vitro. The in vivo drug trials with SCLC-LM mouse model demonstrated that PROTAC EZH2 degrader-1 plus VM26 or cisplatin/ VP16 inhibited H128-LM tumour significantly compared to VM26 or cisplatin/ VP16 alone (P < 0.01). Conclusion: The SCLC-LM model effectively simulates the pathophysiological process of SCLC metastasis to the leptomeninges. PROTAC EZH2 degrader-1 overcomes chemoresistance in SCLC, suggesting its potential therapeutic value for SCLC LM. [ABSTRACT FROM AUTHOR]

The optimization of urban traffic efficiency and reduction of pollution through minimizing the number of taxis has become a topic of increasing interest. However, the problem of determining the minimum fleet that considers both time and distance efficiency has received limited attention. Furthermore, little research has been done on how this problem is influenced by factors such as city size and travel demand (i.e., the number of trips). This study extends the minimum fleet problem to the min-cost minimum fleet problem, and proposes a method to address the problem by constructing a "dispatch network" and finding the minimum weight and minimum path cover of it. A comparative analysis of the method is conducted with the taxi trajectory data of three cities, New York, Chengdu, and Chicago, and the results show a 60% reduction in the off-load travel time of vehicles compared to the previous method, while maintaining the same fleet size. With the introduction of an emissionsmodel and its combination with our methodology, emissions can also be minimized. Moreover, the relationship between min-cost minimum fleet and city size and travel demand (number of trips) is studied. Experimental results indicate that fleet size and idle time (distance) vary linearly with the number of trips. Meanwhile, city size also has an essential impact on the algorithm's performance. Furthermore, these results indicate that the min-cost minimum fleet will help small cities to achieve higher efficiency (smaller fleet and less connection time) than large cities. The acceleration of urbanization is driving changes in the transportation system.Our findings are expected to have significant implications for transport planning, resource conservation, and reducing pollution. [ABSTRACT FROM AUTHOR]

The basis of modern pharmacology is the human ability to exploit the production of specialized metabolites from medical plants, for example, terpenoids, alkaloids, and phenolic acids. However, in most cases, the availability of these valuable compounds is limited by cellular or organelle barriers or spatio‐temporal accumulation patterns within different plant tissues. Transcription factors (TFs) regulate biosynthesis of these specialized metabolites by tightly controlling the expression of biosynthetic genes. Cutting‐edge technologies and/or combining multiple strategies and approaches have been applied to elucidate the role of TFs. In this review, we focus on recent progress in the transcription regulation mechanism of representative high‐value products and describe the transcriptional regulatory network, and future perspectives are discussed, which will help develop high‐yield plant resources. [ABSTRACT FROM AUTHOR]

Rhodium-catalyzed cycloaddition reactions are a powerful tool for the construction of polycyclic compounds. Combined experimental and DFT studies were used to investigate the temperature-controlled chemoselectivity of cationic rhodium-catalyzed intramolecular cycloaddition reactions of ene-vinylidenecyclopropanes. After a series of mechanistic studies, it was found that trace amounts of water in the reaction system play an important role in generating the product with endo double bond located on a five-membered ring and revealed that trace amounts of water in the reaction system, including the rhodium catalyst, substrate and solvent, were sufficient to promote the formation of the product with endo double bond located on a five-membered ring, and additional water could not further accelerate the reaction. DFT calculation results show that the addition of water indeed significantly lowers the energy barrier of the proton transfer step, making the formation of the product with endo double bond located on a five-membered ring more likely to occur and confirming the rationality of water-assisted proton transfer occurring in the selective access to the product with endo double bond located on a five-membered ring. [ABSTRACT FROM AUTHOR]

Introduction: Frailty has an important impact on the health outcomes of older patients, and frailty screening is recommended as part of perioperative evaluation. The Hospital Frailty Risk Score (HFRS) is a validated tool that highlights frailty risk using 109 International Classification of Diseases, 10th revision (ICD-10) codes. In this study, we aim to compare HFRS to the Charlson Comorbidity Index (CCI) and validate HFRS as a predictor of adverse outcomes in Asian patients admitted to surgical services. Method: A retrospective study of electronic health records (EHR) was undertaken in patients aged 65 years and above who were discharged from surgical services between 1 April 2022 to 31 July 2022. Patients were stratified into low (HFRS <5), intermediate (HFRS 5--15) and high (HFRS >15) risk of frailty. Results: Those at high risk of frailty were older and more likely to be men. They were also likely to have more comorbidities and a higher CCI than those at low risk of frailty. High HFRS scores were associated with an increased risk of adverse outcomes, such as mortality, hospital length of stay (LOS) and 30-day readmission. When used in combination with CCI, there was better prediction of mortality at 90 and 270 days, and 30-day readmission. Conclusion: To our knowledge, this is the first validation of HFRS in Singapore in surgical patients and confirms that high-risk HFRS predicts long LOS (≥7days), increased unplanned hospital readmissions (both 30-day and 270-day) and increased mortality (inpatient, 10-day, 30-day, 90-day, 270-day) compared with those at low risk of frailty. [ABSTRACT FROM AUTHOR]

Objectives: Histological transformation to small cell lung cancer (SCLC) has been identified as a mechanism of TKIs resistance in EGFR-mutant non-small cell lung cancer (NSCLC). We aim to explore the prevalence of transformation in EGFR-wildtype NSCLC and the mechanism of SCLC transformation, which are rarely understood. Methods: We reviewed 1474 NSCLC patients to investigate the NSCLC-to-SCLC transformed cases and the basic clinical characteristics, driver gene status and disease course of them. To explore the potential functional genes in SCLC transformation, we obtained pre- and post-transformation specimens and subjected them to a multigene NGS panel involving 416 cancer-related genes. To validate the putative gene function, we established knocked-out models by CRISPR-Cas 9 in HCC827 and A549-TP53-/- cells and investigated the effects on tumor growth, drug sensitivity and neuroendocrine phenotype in vitro and in vivo. We also detected the expression level of protein and mRNA to explore the molecular mechanism involved. Results: We firstly reported an incidence rate of 9.73% (11/113) of SCLC transformation in EGFR-wildtype NSCLC and demonstrated that SCLC transformation is irrespective of EGFR mutation status (P = 0.16). We sequenced 8 paired tumors and identified a series of mutant genes specially in transformed SCLC such as SMAD4, RICTOR and RET. We firstly demonstrated that SMAD4 deficiency can accelerate SCLC transition by inducing neuroendocrine phenotype regardless of RB1 status in TP53-deficient NSCLC cells. Further mechanical experiments identified the SMAD4 can regulate ASCL1 transcription competitively with Myc in NSCLC cells and Myc inhibitor acts as a potential subsequent treatment agent. Conclusions: Transformation to SCLC is irrespective of EFGR status and can be accelerated by SMAD4 in non-small cell lung cancer. Myc inhibitor acts as a potential therapeutic drug for SMAD4-mediated resistant lung cancer. 9vNWjpNbo9djtsBQF6k7BH Video Abstract [ABSTRACT FROM AUTHOR]

Background: Recent case studies indicate that the 2014-2016 Ebola outbreak, one of the worst pre-2020 global biological catastrophes in modern history, helped some nations to better prepared their responses for the COVID-19 pandemic. While such national case studies explore how specific nations applied EVD-related policies in their domestic battle against the COVID-19 pandemic, there is no known study that assesses how many WHO nations learned from the West African crisis and to what scale. Objective: Applying the policy legacies analytical framework and a systematized literature review, this research examines how prior policy experiences with the 2014-16 EVD crisis as a large-scale emergent outbreak helped to inform and to condition WHO nations to proactively prepare their national policies and health systems for future threats, including ultimately COVID-19. Methods: A systematized literature review of 803 evaluated sources assesses to what extent Ebola-affected and non-affected nations directly modified governmental health systems in relation to this warning. The study further evaluates how nations with documented Ebola-related changes fared during COVID-19 compared to nations that did not. We present a categorical theoretical framework that allows for classifying different types of national response activities (termed conditioned learning). Results: Ten (90.9%) of 11 nations that were affected by 2014-16 Ebola crisis have documented evidence of repurposing their EVD-related policies to fight COVID-19. 164 (70.0%) of 234 non-EVD-affected nations had documented evidence of specifically adapting national systems to incorporate policy recommendations developed from the 2014-16 crisis, which informed their COVID-19 responses in 2020. Conclusions: The shock of 2014-16 EVD outbreak affected most nations around the world, whether they experienced Ebola cases. We further develop a categorical framework that helps characterised nations previous experiences with this biological catastrophe, providing a means to analyse to what extent that individual nations learned and how these EVD-related changes helped inform their COVID-19 response. Nations that demonstrated EVD-related conditioned learning nations tended to have more stringent COVID-19 responses before April 2020 and utilized documented response mechanisms developed out of the West African crisis. [ABSTRACT FROM AUTHOR]

Introduction: Mycotic subclavian artery aneurysms (SAAs) are a very rare disorder. Aim: To provide an overview of current knowledge on clinical features, management strategies and outcome evaluations of mycotic SAAs. Material and methods: The study materials were based on comprehensive literature retrieval of publications of mycotic SAAs published between 2000 and 2023. Results: Contaminated mechanical injuries and abscess erosions of the arterial walls are mechanisms of mycotic SAAs. The diagnosis relies on detection of pathogenic microorganisms by cultures or microbiological investigations of blood, other fluids and infected tissues as well as medical imaging visualization. The indications for an interventional therapy were poor general condition, high surgical risk, and rescue exclusion for a ruptured pseudoaneurysm. Three (9.1%) pre-treatment deaths were a result of sudden rupture of the mycotic SAAs and thus they lost the opportunity of treatment. All post-treatment deaths occurred in the interventional patient group, whereas the causes of death seemed to be unrelated to mycotic SAAs per se or to treatments of choice. Patient outcome evaluations revealed no significant difference between different treatments of choice. No significant predictive risk factors were responsible for patient outcomes. Conclusions: Once a diagnosis of mycotic SAA is made, sensitive antibacterial drugs are applied immediately to control the infection and control aneurysmal progression. Early treatment is conducted as soon as possible to avoid aneurysmal rupture. A decision on treatment of choice is made based on the patient’s specific condition. Antibacterial drug use is continued for about 6 weeks after surgical or interventional therapy [ABSTRACT FROM AUTHOR]

This paper employs an MHD-PIC method to perform numerical simulations of magnetic-reconnection-driven turbulence and turbulent reconnection acceleration of particles. Focusing on the dynamics of the magnetic reconnection, the properties of self-driven turbulence, and the behavior of particle acceleration, we find the following: (1) When reaching a statistically steady state of the self-driven turbulence, the magnetic energy is almost released by 50%, while the kinetic energy of the fluid increases by no more than 15%. (2) The properties of reconnection-driven turbulence are more complex than the traditional turbulence driven by an external force. (3) The strong magnetic field tends to enhance the turbulent reconnection efficiency to accelerate particles more efficiently, resulting in a hard spectral energy distribution. Our study provides a particular perspective on understanding turbulence properties and turbulent-reconnection-accelerated particles. [ABSTRACT FROM AUTHOR]

Introduction: Transcatheter aortic valve implantation (TAVI) is the treatment of choice for patients with symptomatic severe aortic stenosis. Aim: To evaluate the neurological event and mortality rates of TAVI in comparison with those of surgical aortic valve replacement (SAVR). Material and methods: A systematic literature search identified pertinent full-text journal articles published from 2000 to 2022 that were taken as the study materials. Results: Patients were at the age of 79.3 ±2.8 years and 79.9 ±2.9 years at the time of intervention/open surgery in the TAVI and SAVR groups, respectively. Patients' age and preoperative comorbidity rates were similar in both groups. A self-expanding valve prosthesis and a percutaneous transfemoral route were the most commonly used in patients receiving TAVI. The duration of the procedure and the hospital stay were much shorter, and the number of transfused blood units was much lower in the TAVI group than in the SAVR group. No significant intergroup difference was found in the prevalence of postoperative stroke, 1-month all-cause mortality, and 1-month and 1-year cardiovascular mortality rates. However, 1-year all-cause mortality was much lower in the TAVI than the SAVR group. The subgroups of risk stratification showed better outcomes for non-high-risk patients compared with high-risk patients. Conclusions: Irrespective of other postoperative complications of TAVI, this study emphasizes the postoperative major neurological events and mortality. TAVI appears to be superior to SAVR with regard to 1-year all-cause mortality. TAVI is thus recommended for elderly patients with symptomatic severe aortic stenosis at very high surgical risk contraindicated for SAVR. [ABSTRACT FROM AUTHOR]

Background: Hepatic masses are relatively common findings, and the diagnostic approach often begins by identifying patient and mass characteristics that are risk factors for malignancy. Chronic immunosuppression is a known risk factor for various malignancies, and azathioprine in particular has been reported in association with solid and hematologic malignancies, including diffuse large B-cell lymphoma. Case presentation: A 46-year-old white woman presented to clinic with several weeks of gastrointestinal symptoms and was found to have a hepatic mass on imaging. Her history was notable for neuromyelitis optica spectrum disorder on chronic immunosuppression with azathioprine. It was initially thought to be an inflammatory adenoma. On 6-month follow-up imaging, the mass had grown rapidly in size and was surgically resected. Further workup determined the mass to be an iatrogenic immunodeficiency-associated Epstein–Barr virus-positive diffuse large B-cell lymphoma confined to the liver. Azathioprine was discontinued and the patient underwent treatment with rituximab with no evidence of recurrence 2 years after the initiation of treatment. Conclusions: This case report describes the first time hepatic Epstein–Barr virus-positive diffuse large B-cell lymphoma has been reported with azathioprine, which highlights the unique sequelae of chronic immunosuppression, including atypical hematologic malignancies, and the importance of considering chronic immunosuppression in the diagnostic evaluation of a hepatic mass. [ABSTRACT FROM AUTHOR]

In this work, TiO2-MXene/poly (3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) composite was utilized as an electrode material for the sensitive electrochemical detection of baicalein. The in-situ growth of TiO2 nanoparticles on the surface of MXene nanosheets can effectively prevent their aggregation, thus presenting a significantly large specific surface area and abundant active sites. However, the partial oxidation of MXene after calcination could reduce its conductivity. To address this issue, herein, PEDOT:PSS films were introduced to disperse the TiO2-MXene materials. The uniform and dense films of PEDOT:PSS not only improved the conductivity and dispersion of TiO2-MXene but also enhanced its stability and electrocatalytic activity. With the advantages of a composite material, TiO2-MXene/PEDOT:PSS as an electrode material demonstrated excellent electrochemical sensing ability for baicalein determination, with a wide linear response ranging from 0.007 to 10.0 μM and a lower limit of detection of 2.33 nM. Furthermore, the prepared sensor displayed good repeatability, reproducibility, stability and selectivity, and presented satisfactory results for the determination of baicalein in human urine sample analysis. [ABSTRACT FROM AUTHOR]

High utility sequential pattern (HUSP) mining aims to mine actionable patterns with high utilities, widely applied in real-world learning scenarios such as market basket analysis, scenic route planning and click-stream analysis. The existing HUSP mining algorithms mainly attempt to improve computation efficiency while maintaining the algorithm stability in the setting of large-scale data. Although these methods have made some progress, they ignore the relationship between additional items and underlying sequences, which directly leads to the generation of redundant sequential patterns sharing the same underlying sequence. Hence, the mined patterns' actionability is limited, which significantly compromises the performance of patterns in real-world applications. To address this problem, we present a new method named Combined Utility-Association Sequential Pattern Mining (CUASPM) by incorporating item/sequence relations, which can effectively remove redundant patterns and extract high discriminative and strongly associated sequential pattern combinations with high utilities. Specifically, we introduce the concept of actionable combined mining into HUSP mining for the first time and develop a novel tree structure to select discriminative high utility sequential patterns (HUSPs) for downstream tasks. Furthermore, two efficient strategies (i.e., global and local strategies) are presented to facilitate mining HUSPs while guaranteeing utility growth and high levels of association. Last, two parameters are introduced to evaluate the interestingness of patterns to choose the most useful actionable combined HUSPs (ACHUSPs). Extensive experimental results demonstrate that the proposed CUASPM outperforms the baselines in terms of execution time, memory usage, mining high discriminative and strongly associated HUSPs. [ABSTRACT FROM AUTHOR]

Directed differentiation of human pluripotent stem cells (hPSCs) into functional ureteric and collecting duct (CD) epithelia is essential to kidney regenerative medicine. Here we describe highly efficient, serum-free differentiation of hPSCs into ureteric bud (UB) organoids and functional CD cells. The hPSCs are first induced into pronephric progenitor cells at 90% efficiency and then aggregated into spheres with a molecular signature similar to the nephric duct. In a three-dimensional matrix, the spheres form UB organoids that exhibit branching morphogenesis similar to the fetal UB and correct distal tip localization of RET expression. Organoid-derived cells incorporate into the UB tips of the progenitor niche in chimeric fetal kidney explant culture. At later stages, the UB organoids differentiate into CD organoids, which contain >95% CD cell types as estimated by single-cell RNA sequencing. The CD epithelia demonstrate renal electrophysiologic functions, with ENaC-mediated vectorial sodium transport by principal cells and V-type ATPase proton pump activity by FOXI1-induced intercalated cells. Kidney collecting duct cells with physiologic functions are generated from human pluripotent stem cells. [ABSTRACT FROM AUTHOR]

The oxidative state of intestinal tracts of healthy animals were investigated after short-term intake of half-fin anchovy hydrolysates (HAHp) and their thermal or Maillard reaction products (MRPs). After one month of continuous oral gavage of HAHp, HAHp-heated products (HAHp-H), the MRPs of HAHp with 3% of glucose (HAHp-3%G MRPs), and the MRPs of HAHp with 3% of fructose (HAHp-3%F MRPs) at a dose of 1.0 g/kg of body weight per day into healthy ICR male mice, the concentrations of serum low-density and high-density lipoprotein cholesterol did not significantly change compared to the control group (CK, gavage with saline). Similar results were found for the interleukin-6 concentrations of all groups. By comparison, HAHp-H, HAHp-3%G MRPs, and HAHp-3%F MRPs administration decreased serum tumor necrosis factor-α concentration as compared to the CK group (p < 0.05). No histological damage was observed in the jejunum, ileum, and colonic tissues of all groups. However, HAHp-H treatment induced higher upregulation of Kelch-like ECH-associated protein 1, transcription factors Nrf-2, associated protective phase-II enzymes of NAD(P)H: quinine oxidoreductase-1, and hemoxygenase-1 in colon tissue, as well as higher upregulation of endogenous antioxidant enzymes, including copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, and glutathione peroxidase 2 than other groups (p < 0.05). Additionally, increases in Nε-carboxymethyllysine expression in the colonic tissues of all groups were consistent with their increased oligopeptide transporter 1 expressions. Our results suggest that the thermal products of HAHp might have a broad application prospect in improving antioxidant defense in vivo in healthy animals. [ABSTRACT FROM AUTHOR]

In Situ microfibrillation is an easy and economical processing method, which has drawn wide concern in recent years. In Situ special-shaped microfibrillar composites, which with poly(lactic acid)/polyamide 6 (PA6/PLA) together formed special-shaped microfibrils in polyolefin elastomer (POE) matrix, were successfully prepared by using multistage stretching extrusion technology. Four types of PA6 with different viscosity were utilized to investigate the effect of viscosity ratio of PA6 to PLA on the structure evolution of special-shaped microfibrils and the mechanical properties of POE/(PA6/PLA) composites. The morphological observation showed that the viscosity ratio was closely associated to the size and shape of PA6 and greatly affected the microfibrillar morphology of PLA/PA6. When the viscosity ratio of PA6 to PLA was less than 2.2, the "gourd-skewers-like" structure microfibrils were obtained. When the viscosity ratio of PA6/PLA to 14.2 was further increased, the "trepang" structure microfibrils were dominant. The "gourd skewers" structure microfibrils were favorable to improvement the tensile strength, Young's modulus, and viscoelastic properties of POE/(PA6/PLA) blends compared to the "trepang" structure microfibrils. In addition, the morphology of microfibrils exhibited a negligible effect on the melting and crystallization temperature and crystallization degree of PLA and POE matrix. This work provides a new strategy for designing the in situ special-shaped microfibrillar composites with improved mechanical properties. [ABSTRACT FROM AUTHOR]

C13-norisoprenoids are of particular importance to grapes and wines, as these molecules influence wine aroma and have been shown to significantly contribute to the distinct character of various wine varieties. Blumenol B is a putative precursor to a number of important wine aroma compounds, including the well-known compounds theaspirone and vitispirane. The enantioselective synthesis of (R,R)-blumenol B from commercially available 4-oxoisophorone was achieved using a short and easily scaleable route, which was then successfully applied to the synthesis of poly-deuterated d9-blumenol B. [ABSTRACT FROM AUTHOR]

In humans, a family of 25 bitter taste receptors (TAS2Rs) mediates bitter taste perception. A common approach to characterize bitter causative agents involves expressing TAS2Rs and the appropriate signal transducers in heterologous cell systems, and monitoring changes in the intracellular free calcium levels upon ligand exposure using a fluorescence-based modality, which typically suffers from a low signal window, and is susceptible to interference by autofluorescence, therefore prohibiting its application to screening of plant or food extracts, which are likely to contain autofluorescent compounds. The aim of this study is to develop and validate a bioluminescence-based intracellular calcium release assay for TAS2Rs that has a better assay performance than a fluorescence-based assay. Furthermore, the bioluminescence-based assay enabled the evaluation of TAS2R agonists within an autofluorescent matrix, highlighting its potential utility in the assessment of the bitterness-inducing properties of plant or food fractions by the food industry. Additionally, improvement to the bioluminescence-based assay for some TAS2Rs was achieved by altering their N-terminal signal sequences, leading to signal window enhancement. Altogether, the bioluminescence-based TAS2R assay can be used to perform functional studies of TAS2Rs, evaluate TAS2R-modulating properties of autofluorescent samples, and facilitate the discovery of compounds that can function as promising bitter taste modulators. [ABSTRACT FROM AUTHOR]

In this work, a two-dimensional leaf-like framework-L embedded electrochemically reduced graphene oxide (ERGO@ZIF-L) was proposed as an outstanding electrode material for the sensitive electrochemical sensing of benomyl (BM). ZIF-L is surrounded by ERGO, which could effectively ensure the stability and dispersion of ZIF-L. With this unique combination, the prepared ERGO@ZIF-L displayed excellent synergistic characteristics with a large surface area, excellent conductivity, plentiful active sites, and high electrocatalytic properties, thus endowing it with high sensitivity for BM determination. The experimental parameters, such as solution pH, material volume, and accumulation time, were optimized. Under optimal conditions, the BM sensor showed a wide linear range (0.009–10.0 μM) and low-limit detection (3.0 nM). Moreover, the sensor displayed excellent stability, repeatability, and reproducibility, and good anti-interference capability. The method was successfully applied to detect BM in real-world samples. [ABSTRACT FROM AUTHOR]

Obesity is a leading global health problem contributing to various chronic diseases, including type II diabetes mellitus (T2DM). The aim of this study was to investigate whether blueberries, yoghurt, and their respective bioactive components, Cyanidin-3-O-β-glucoside (C3G) and peptides alone or in combinations, alter the expression of genes related to glucose metabolism in skeletal muscles from diet-induced obese mice. In extensor digitorum longus (EDL), yoghurt up-regulated the expression of activation of 5'adenosine monophosphate-activated protein kinase (AMPK), insulin receptor substrate-1 (IRS-1), phosphatidylinositol-3 kinase (PI3K) and glucose transporter 4 (GLUT4), and down-regulated the expression of angiotensin II receptor type 1 (AGTR-1). The combination of blueberries and yoghurt down-regulated the mRNA expression of AGTR-1 and Forkhead box protein O1 (FoxO1) in the EDL. Whereas the combination of C3G and peptides down-regulated AGTR-1 and up-regulated GLUT4 mRNA expression in the EDL. In the soleus, blueberries and yoghurt alone, and their combination down-regulated AGTR-1 and up-regulated GLUT4 mRNA expression. In summary blueberries and yoghurt, regulated multiple genes associated with glucose metabolism in skeletal muscles, and therefore may play a role in the management and prevention of T2DM. [ABSTRACT FROM AUTHOR]

This perceptual study focuses on developing artificial intelligence for elderly care design. It analyses and discusses the role of artificial intelligence in elderly care and its application to physiotherapy care. Artificial intelligence, as an emerging disruptive technology, is releasing the enormous energy accumulated in the technological and industrial revolutions, profoundly transforming how humans produce, live, and think about the world. Economic development and social progress are significantly impacted by it, and it has a great deal of practicality and broad application scope. Although there is a basic consensus in the 18 public understanding of AI, there is still some ambiguity and misunderstanding, knowing what is happening without understanding why. As a result, it is necessary to systematize and gain a comprehensive understanding of this concept and its associated practices. [ABSTRACT FROM AUTHOR]

The compositional similarity between high‐Mg andesite‐dacite from accretionary orogens and bulk continental crust (CC) provides an opportunity to unravel the CC formation paradox. Compositional data from a global compilation of Quaternary magmatic arcs indicate the presence of low‐Mg series (LMS) and high‐Mg series (HMS). The LMS show trends of crystal fractionation and can be subdivided into high Ba/Th and high La/Sm groups, which likely originate from fluid‐ and sediment melt‐modified mantle wedge, respectively. In contrast, the HMS have variably mixed compositions (e.g., high Mg#, Ba/Th, and La/Sm) and can be explained by partial melting of mélange diapirs rising into the mantle wedge, which are mixtures of subducted sediment, eroded arc crust or CC, buoyant oceanic crust, and peridotite. We, therefore, propose a two‐step process for creating CC involving extraction of LMS from the mantle followed by re‐melting of recycled LMS in the mantle to generate HMS and thus CC. Plain Language Summary: Continental crust (CC) is extracted from the mantle primarily by subduction‐related magmatism in accretionary orogens. However, igneous rocks sourced from the mantle have low SiO2 (basalt), whereas average CC has high SiO2 (andesite) and high MgO. To resolve this paradox, we analyzed Quaternary subduction‐related igneous rocks worldwide and find that they can be divided into low‐Mg series (LMS) and high‐Mg series (HMS). We compare existing compositional data for LMS and HMS and find that LMS are dominated by basalt whereas HMS are dominated by andesite and similar to the average CC. Petrogenetic analyses reveal that LMS likely originate from the mantle and represent primitive CC, whereas HMS likely originate from recycled crustal materials in the mantle and represent mature CC. We propose a two‐step process for creating CC, involving extraction of LMS from the mantle followed by re‐melting of recycled LMS to generate HMS and thus CC. Our results provide a new solution to the CC formation paradox. Key Points: Low‐Mg series (LMS) arc igneous rocks originate from fluid‐/sediment melt‐modified mantle wedge, followed by crystal fractionationHigh‐Mg series (HMS) arc igneous rocks likely originate from recycled crustal materials as mélange diapirs rising into the mantle wedgeContinental crust is formed by extracting LMS from the mantle followed by re‐melting of recycled LMS in the mantle wedge to generate HMS [ABSTRACT FROM AUTHOR]

We appreciate the interest by Drs. Hagiyama and coauthors in our work entitled "Calcar fracture gapping: a reliable predictor of anteromedial cortical support failure after cephalomedullary nailing for pertrochanteric femur fractures". They discussed several pertinent points and it is our pleasure to respond their concerns in order. Firstly, we agree that calcar fracture gap and anteromedial cortical support are different concepts, though both of them were used to evaluate the displacement of fracture reduction quality. Secondly, our primary outcome parameter was the threshold distance of calcar fracture gapping in anteroposterior and lateral fluoroscopies, which was calculated based on sensitivity and specificity by receiver operating characteristic curves. Thirdly, we took immediate post-operative fluoroscopic images in 3 views to describe the initial reduction quality as baseline to compare and calculate the changes with three-dimensional computed tomography, which was taken about one week after operation for confirming secondary stability after head-neck sliding and impaction. Lastly, the parameters selected in multivariable analysis. Future work with better study-design is needed to improve the prediction of patient outcomes. [ABSTRACT FROM AUTHOR]

We appreciate the interest by Drs. Hagiyama and coauthors in our work entitled "Calcar fracture gapping: a reliable predictor of anteromedial cortical support failure after cephalomedullary nailing for pertrochanteric femur fractures". They discussed several pertinent points and it is our pleasure to respond their concerns in order. Firstly, we agree that calcar fracture gap and anteromedial cortical support are different concepts, though both of them were used to evaluate the displacement of fracture reduction quality. Secondly, our primary outcome parameter was the threshold distance of calcar fracture gapping in anteroposterior and lateral fluoroscopies, which was calculated based on sensitivity and specificity by receiver operating characteristic curves. Thirdly, we took immediate post-operative fluoroscopic images in 3 views to describe the initial reduction quality as baseline to compare and calculate the changes with three-dimensional computed tomography, which was taken about one week after operation for confirming secondary stability after head-neck sliding and impaction. Lastly, the parameters selected in multivariable analysis. Future work with better study-design is needed to improve the prediction of patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Maintaining anteromedial cortical support is essential for controlling sliding and decreasing postoperative implant-related complications. However, adequate fracture reduction with cortical support in immediate postoperative fluoroscopy is not invariable in postoperative follow-ups. This study was conducted to investigate the risk factors leading to anteromedial cortical support failure in follow up for pertrochanteric femur fractures treated with cephalomedullary nails. Methods: This retrospective study enrolled 159 patients with pertrochanteric fractures (AO/OTA- 31A1 and 31A2) that fixed with cephalomedullary nails. All patients were evaluated as adequate fracture reduction in immediate postoperative fluoroscopy before leaving the operation theater. The patients were separated into two groups based on the condition of the anteromedial cortex in the postoperative 3D CT with full-range observation: those with calcar support maintained in Group 1 and those with calcar support lost in Group 2. Demographic information, fracture classification, TAD (tip-apex distance), Cal-TAD, Parker ratio, NSA (neck-shaft angle), reduction quality score, and calcar fracture gapping were collected and compared. Logistic regression analysis was conducted to explore the risk factors leading to anteromedial cortex change. Results: Anteromedial cortical support failure was noted in 46 cases (29%). There was no significant difference between the two groups concerning age, sex, side injury, TAD, Cal-TAD, Parker ratio, or NSA. There was a significant difference in the AO/OTA fracture classification in univariate analysis but no difference in the multivariable analysis. The reduction quality score, calcar fracture gapping in the AP (anteroposterior), and lateral views were significantly associated with anteromedial cortical support failure in follow-up after cephalomedullary nailing in the multivariable analysis. The threshold value of calcar fracture gapping for the risk of loss was 4.2 mm in the AP and 3.8 mm in the lateral fluoroscopies. Mechanical complications (lateral sliding and varus) were frequently observed in the negative anteromedial cortical support group. Conclusions: Good reduction quality was a protective factor, and larger calcar fracture gapping in the AP and lateral views were risk factors leading to the postoperative loss of anteromedial cortical support. Therefore, we should pay close attention to fracture reduction and minimize the calcar fracture gap during surgery. [ABSTRACT FROM AUTHOR]

Background: Maintaining anteromedial cortical support is essential for controlling sliding and decreasing postoperative implant-related complications. However, adequate fracture reduction with cortical support in immediate postoperative fluoroscopy is not invariable in postoperative follow-ups. This study was conducted to investigate the risk factors leading to anteromedial cortical support failure in follow up for pertrochanteric femur fractures treated with cephalomedullary nails. Methods: This retrospective study enrolled 159 patients with pertrochanteric fractures (AO/OTA- 31A1 and 31A2) that fixed with cephalomedullary nails. All patients were evaluated as adequate fracture reduction in immediate postoperative fluoroscopy before leaving the operation theater. The patients were separated into two groups based on the condition of the anteromedial cortex in the postoperative 3D CT with full-range observation: those with calcar support maintained in Group 1 and those with calcar support lost in Group 2. Demographic information, fracture classification, TAD (tip-apex distance), Cal-TAD, Parker ratio, NSA (neck-shaft angle), reduction quality score, and calcar fracture gapping were collected and compared. Logistic regression analysis was conducted to explore the risk factors leading to anteromedial cortex change. Results: Anteromedial cortical support failure was noted in 46 cases (29%). There was no significant difference between the two groups concerning age, sex, side injury, TAD, Cal-TAD, Parker ratio, or NSA. There was a significant difference in the AO/OTA fracture classification in univariate analysis but no difference in the multivariable analysis. The reduction quality score, calcar fracture gapping in the AP (anteroposterior), and lateral views were significantly associated with anteromedial cortical support failure in follow-up after cephalomedullary nailing in the multivariable analysis. The threshold value of calcar fracture gapping for the risk of loss was 4.2 mm in the AP and 3.8 mm in the lateral fluoroscopies. Mechanical complications (lateral sliding and varus) were frequently observed in the negative anteromedial cortical support group. Conclusions: Good reduction quality was a protective factor, and larger calcar fracture gapping in the AP and lateral views were risk factors leading to the postoperative loss of anteromedial cortical support. Therefore, we should pay close attention to fracture reduction and minimize the calcar fracture gap during surgery. [ABSTRACT FROM AUTHOR]

Introduction: Refractory arrhythmias during pregnancy pose challenges to physicians. Aim: To give an overview of catheter ablation for tachyarrhythmias during pregnancy, and to discuss the indications of the procedure and the outcomes of both mother and fetus. Material and methods: The study materials were based on comprehensive literature retrieval of the pertinent articles published since 2000. Results: The indications for catheter ablation were refractory arrhythmias unresponsive to drug therapy in most of the cases followed by requirement of cardioversion. Atrioventricular nodal reentrant tachycardia was the most common arrhythmia developed during pregnancy. Pregnancy complications were present in 2.4% of the cases. There was no mortality among the pregnant patients. Fetal adverse events occurred in 3.1% of the cases, more in the fluoroscopy than in the zero-fluoroscopy group. The patient cohort with a radiation dose of > 50 mGy in one-third of the cases had a 14.3% fetal adverse event rate. Fetal adverse events occurred only in the second trimester, not in the other two trimesters. Conclusions: Drug-refractory and poorly tolerated tachycardias in pregnant patients warrant catheter ablation. Zero-fluoroscopy technique under guidance with three-dimensional mapping systems is preferred and strict minimal fluoroscopy is only used in extreme necessity. As ablation in the second trimester was associated with a probable higher fetal adverse event rate, it is suggested that ablation is preferably performed in the third trimester. [ABSTRACT FROM AUTHOR]

In this work, carbon nanohorn (CNH)–decorated multi-walled carbon nanotube (MWCNT) (CNH@MWCNT) composite was prepared and used to modify glass carbon electrode (GCE) as sensitive electrochemical sensor for niclosamide (NA) determination. Herein, the decoration of CNHs induces higher dispersibility for MWCNTs, and endows the composite with better conductivity, larger surface area, and higher catalytic activity, which leads to significantly enhanced electrochemical behavior toward NA oxidation. The parameters such as mass ratios of CNHs and MWCHTs, the amount of composite materials, the accumulation time, and the solution pH are systematically optimized. Under optimized conditions, the developed electrochemical sensor exhibits a low detection limit of 2.0 nM with a wide linear range of 7.0 nM–10.0 µM and high anti-interference ability. In addition, the sensor displays good stability, repeatability, and reproducibility. The feasibility of the assay was verified by testing NA in brown rice and rice field water samples. [ABSTRACT FROM AUTHOR]

Novel Li 1.0 Nb 0.6 Ti 0.5 O 3 : Tb3+ ceramics with favorable luminescent and dielectric properties were prepared by solid-state reaction (SSR) method. The X-ray diffraction (XRD) results indicated that the Tb3+ ions were effectively dissolved into the "M-phase" matrix synthesized at 1000–1100°C. The ceramic with a dense microstructure could be obtained at 1050°C. The Li 1.0 Nb 0.6 Ti 0.5 O 3 : Tb3+ ceramics emitted green light at 550 nm and relatively strong red light at 660 nm under the excitation of 440 nm, which were located in the orange-red light region shown in the chromaticity diagram. The color coordinates were (0.5574, 0.4417) for the Li 1.0 Nb 0.6 Ti 0.5 O 3 : 2wt% Tb3+ ceramic sintered at 1050°C. The quantum efficiency of Li 1.0 Nb 0.6 Ti 0.5 O 3 : 2wt%Tb3+ ceramic was 19%, which was much higher than that of 9.6% for commercial red Y 2 O 3 : Eu3+ phosphors. Furthermore, for Li 1.0 Nb 0.6 Ti 0.5 O 3 : 2wt%Tb3+ ceramic synthesized at 1050°C, the ideal dielectric properties with ε r of 66.263 and Q*f of 5582 GHz were obtained, which might be used as a potentially multifunctional ceramic applied in the fields of LED packaging to improve the lack of red light for blue LEDs combined with yellow phosphors. [ABSTRACT FROM AUTHOR]

Objective: Four and a half Lin-11, Isl-1, Mac-3 (LIM) protein 1 (FHL1) is one of the FHL protein family, which is regarded as a tumor suppressor in the multiple malignant tumors. In this study, we aimed to explore the regulatory effects and mechanisms of FHL1 on lung cancer cell invasion. Materials and Methods: In this experimental study, bioinformatics analysis of FHL1 transcripts in human lung adenocarcinomas of TCGA database was performed. Quantitative real-time polymerase chain reaction (PCR) was performed to detect FHL1 mRNA expression in 15 paired human lung cancer tissues and their adjacent normal lung tissues, or lung cancer cell lines (A549 and H1299) in comparison with human bronchial epithelial cell line (Beas2B). Moreover, western blot was used to analyze FHL1 and rho GDP-dissociation inhibitor beta (RhoGDIβ) protein expression in the indicated cell lines. Also, transwell assays were employed to measure the migrated, and invaded of indicated cell lines. Results: FHL1 transcripts were downregulated in the human lung adenocarcinoma. The impaired FHL1 transcripts were positively correlated with advanced tumor node metastasis (TNM) stage. Moreover, as compared to the adjacent normal lung tissues, FHL1 mRNA was low expressed in 15 paired human lung cancer tissues than their adjacent normal lung tissues. Besides, FHL1 mRNA and protein expression were also reduced in H1299 and A549 cell lines in comparison with Beas-2B cell line. Overexpressed FHL1 protein inhibited the invasive ability of H1299 and A549 cell lines. Mechanically, FHL1 protein overexpression increased the RhoGDIβ protein and mRNA abundance, while knockdown of RhoGDIβ protein, completely restored the invasion ability of A549 (Flag-FHL1) cell line. Conclusion: Our findings indicated that as a key FHL1 downstream regulator, RhoGDIβ is in charge of FHL1 inhibiting lung cancer cell invasion abilities, providing a critical insight into understanding the role of FHL1 for lung cancer development. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the association between autoimmune thyroiditis and Sudden Sensorineural Hearing Loss (SSNHL). Methods: Hundred and five patients with SSNHL were enrolled. Audiometric tests, serum thyroid autoantibodies (TPOAb, TgAb) were studied. Based on the thyroid autoantibody results, patients were divided into two groups: thyroid autoantibody‐positive and negative. The relationship between thyroid autoimmunity and audiological characteristics was analyzed. Results: Twenty‐six patients (24.8%) of the SSNHL had thyroid autoantibody elevated. The pure tone average (PTA) of patients with and without thyroid autoantibody is 60 ± 38.51 and 54.99 ± 33.87 dBHL, respectively. The PTA was significantly improved in both groups after treatment (p < 0.001), but the hearing gains were similar in both groups (p = 0.205). Hearing loss of 2000–8000 Hz was worse than 125–1000 Hz among thyroid autoantibody‐positive patients (p < 0.05), but the hearing improvement of both groups have no significant difference. The hearing improvement of 125–1000 Hz is significantly better than 2000–8000 Hz among patients with thyroid autoantibody negative (p < 0.05). Conclusions: We speculate that a potential association between thyroid autoimmunity and SSNHL. Thyroid autoimmunity may be a pathogenesis factor of SSNHL and associated with more severe hearing loss of high‐frequency hearing. [ABSTRACT FROM AUTHOR]

Alagille syndrome, caused by mutations in the gene encoding Jagged1 (JAG1), a ligand in the Notch signaling pathway, is an autosomal dominant disorder with developmental abnormalities affecting the liver, heart, eyes, face and skeleton. The aim of the present study is try to disclose the clinical features, management and outcomes of pulmonary artery stenosis associated with Alagille syndrome. By comprehensive literature retrieval, 38 articles involving 401 patients were recruited for this study. The pertinent variables closely related to pulmonary artery stenosis in patients with Alagille syndrome were comprehensively analyzed by following the PRISMA guidelines. The management of pulmonary artery pathologies, especially a severe type of pulmonary artery stenosis in Alagille syndrome, is a concerned matter. Publications of literature retrieval of recent 3 decades were the study material of this article. The pulmonary artery pathologies, especially the severe type of pulmonary artery stenosis in Alagille syndrome, warrant surgical or interventional treatments. After the procedures, the right ventricular to left ventricular pressure ratio was reduced by 25%. There were no intergroup differences in terms of recovery, reintervention and mortality rates between interventionally and surgically treated patients. Transcatheter treatment is preferable due to less trauma. Surgical treatment of pulmonary artery stenosis can be performed currently with intracardiac defect repair. [ABSTRACT FROM AUTHOR]

The aim of the present study is to describe the indications, treatment effects, and patient outcomes of percutaneous management of left ventricular pseudoaneurysm (LVPA). The study materials were based on comprehensive literature retrieval since 2004. The mechanisms of LVPA formation can be divided into surgical, percutaneous, and medial disease related. Of the surgical mechanisms, coronary artery bypass grafting prevailed. The formation time was the longest in medical disease-related LVPAs up to 44.4 months. The percutaneous procedures succeeded on the first try in 79 (84.9%) patients, whereas failures were encountered during the percutaneous manoeuvres in 14 (15.1%) patients. Percutaneous closure of LVPA was especially indicated for patients carrying a high surgical risk. The iatrogenic traumas, such as left ventricular venting, should be avoided to prevent this complication. The preliminary cut-off valves of oversize 3.3 mm and oversize ratio 1.6 should be followed for reference for device choice. [ABSTRACT FROM AUTHOR]

Background: Ophiorrhiza pumila (Rubiaceae) is capable of producing camptothecin (CPT), one monoterpene indole alkaloid extensively employed in the treatment of multiple cancers. Transcription factors (TFs) GATA are a group of transcription regulators involved in plant development and metabolism, and show the feature of binding to the GATA motif within the promoters of target genes. However, GATA TFs have not been characterized in O. pumila. Result: In this study, a total of 18 GATA genes classified into four subfamilies were identified, which randomly distributed on 11 chromosomes of O. pumila. Synteny analysis of GATA genes between O. pumila and other plant species such as Arabidopsis thaliana, Oryza sativa, Glycine max, Solanum lycopersicum, Vitis vinifera, and Catharanthus roseus genomes were analyzed. Tissue expression pattern revealed that OpGATA1 and OpGATA18 were found to be correlated with ASA, MK, CPR and GPPS, which were highly expressed in leaves. OpGATA7, showed high expression in roots as most of the CPT biosynthetic pathway genes did, suggesting that these OpGATAs may be potential candidates regulating CPT biosynthesis in O. pumila. Conclusions: In this study, we systematically analyzed the OpGATA TFs, and provided insights into the involvement of OpGATA TFs from O. pumila in CPT biosynthesis. [ABSTRACT FROM AUTHOR]

Background: Maintaining anteromedial cortical support is essential for controlling sliding and decreasing postoperative implant-related complications. However, adequate fracture reduction with cortical support in immediate postoperative fluoroscopy is not invariable in postoperative follow-ups. This study was conducted to investigate the risk factors leading to anteromedial cortical support failure in follow up for pertrochanteric femur fractures treated with cephalomedullary nails.Methods: This retrospective study enrolled 159 patients with pertrochanteric fractures (AO/OTA- 31A1 and 31A2) that fixed with cephalomedullary nails. All patients were evaluated as adequate fracture reduction in immediate postoperative fluoroscopy before leaving the operation theater. The patients were separated into two groups based on the condition of the anteromedial cortex in the postoperative 3D CT with full-range observation: those with calcar support maintained in Group 1 and those with calcar support lost in Group 2. Demographic information, fracture classification, TAD (tip-apex distance), Cal-TAD, Parker ratio, NSA (neck-shaft angle), reduction quality score, and calcar fracture gapping were collected and compared. Logistic regression analysis was conducted to explore the risk factors leading to anteromedial cortex change.Results: Anteromedial cortical support failure was noted in 46 cases (29%). There was no significant difference between the two groups concerning age, sex, side injury, TAD, Cal-TAD, Parker ratio, or NSA. There was a significant difference in the AO/OTA fracture classification in univariate analysis but no difference in the multivariable analysis. The reduction quality score, calcar fracture gapping in the AP (anteroposterior), and lateral views were significantly associated with anteromedial cortical support failure in follow-up after cephalomedullary nailing in the multivariable analysis. The threshold value of calcar fracture gapping for the risk of loss was 4.2 mm in the AP and 3.8 mm in the lateral fluoroscopies. Mechanical complications (lateral sliding and varus) were frequently observed in the negative anteromedial cortical support group.Conclusions: Good reduction quality was a protective factor, and larger calcar fracture gapping in the AP and lateral views were risk factors leading to the postoperative loss of anteromedial cortical support. Therefore, we should pay close attention to fracture reduction and minimize the calcar fracture gap during surgery. [ABSTRACT FROM AUTHOR]

Motivation Epistasis may play an etiologic role in complex diseases, but research has been hindered because identification of interactions among sets of single nucleotide polymorphisms (SNPs) requires exploration of immense search spaces. Current approaches using nuclear families accommodate at most several hundred candidate SNPs. Results GADGETS detects epistatic SNP-sets by applying a genetic algorithm to case-parent or case-sibling data. To allow for multiple epistatic sets, island subpopulations of SNP-sets evolve separately under selection for evident joint relevance to disease risk. The software evaluates the identified SNP-sets via permutation testing and provides graphical visualization. GADGETS correctly identified epistatic SNP-sets in realistically simulated case-parent triads with 10 000 candidate SNPs, far more SNPs than competitors can handle, and it outperformed competitors in simulations with many fewer SNPs. Applying GADGETS to family-based oral-clefting data from dbGaP identified SNP-sets with possible epistatic effects on risk. Availability and implementation GADGETS is part of the epistasisGA package at https://github.com/mnodzenski/epistasisGA. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Background: Freezing stress inhibits plant development and causes significant damage to plants. Plants therefore have evolved a large amount of sophisticated mechanisms to counteract freezing stress by adjusting their growth and development correspondingly. Plant ontogenetic defense against drought, high salt, and heat stresses, has been extensively studied. However, whether the freezing tolerance is associated with ontogenetic development and how the freezing signals are delivered remain unclear. Results: In this study, we found that the freezing tolerance was increased with plant age at the vegetative stage. The expressions of microRNA156 (miR156) and SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 9 (SPL9), playing roles in regulation of ontogenetic development, were induced by cold stress. Overexpression of SPL9 (rSPL9) promoted the expression of C-REPEAT BINDING FACTOR 2 (CBF2) and hereafter enhanced the freezing tolerance. Genetic analysis indicated that the effect of rSPL9 on freezing tolerance is partially restored by cbf2 mutant. Further analysis confirmed that SPL9 directly binds to the promoter of CBF2 to activate the expression of CBF2, and thereafter increased the freezing tolerance. Conclusions: Therefore, our study uncovers a new role of SPL9 in fine-tuning CBF2 expression and thus mediating freezing tolerance in plants, and implies a role of miR156-SPL pathway in balancing the vegetative development and freezing response in Arabidopsis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the molecular characteristics in tumor immune microenvironment that affect long-term survival of patients with pancreatic adenocarcinoma (PAAD). Methods: The tumor related genetic features of a female PAAD patient (over 13-year survival) who suffered from multiple recurrences and metastases, and six operations over one decade were investigated deeply. Genomic features and immune microenvironment signatures of her primary lesion as well as six metastatic tumors at different time-points were characterized. Results: High-frequency clonal neoantigenic mutations identified in these specimens revealed the significant associations between clonal neoantigens with her prognosis after each surgery. Meanwhile, the TCGA and ICGC databases were employed to analyse the function of KRAS G12V in pancreatic cancer. Conclusions: The genomic analysis of clonal neoantigens combined with tumor immune microenvironment could promote the understandings of personalized prognostic evaluation and the stratification of resected PAAD individuals with better outcome. [ABSTRACT FROM AUTHOR]

Background: Freezing stress inhibits plant development and causes significant damage to plants. Plants therefore have evolved a large amount of sophisticated mechanisms to counteract freezing stress by adjusting their growth and development correspondingly. Plant ontogenetic defense against drought, high salt, and heat stresses, has been extensively studied. However, whether the freezing tolerance is associated with ontogenetic development and how the freezing signals are delivered remain unclear. Results: In this study, we found that the freezing tolerance was increased with plant age at the vegetative stage. The expressions of microRNA156 (miR156) and SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 9 (SPL9), playing roles in regulation of ontogenetic development, were induced by cold stress. Overexpression of SPL9 (rSPL9) promoted the expression of C-REPEAT BINDING FACTOR 2 (CBF2) and hereafter enhanced the freezing tolerance. Genetic analysis indicated that the effect of rSPL9 on freezing tolerance is partially restored by cbf2 mutant. Further analysis confirmed that SPL9 directly binds to the promoter of CBF2 to activate the expression of CBF2, and thereafter increased the freezing tolerance. Conclusions: Therefore, our study uncovers a new role of SPL9 in fine-tuning CBF2 expression and thus mediating freezing tolerance in plants, and implies a role of miR156-SPL pathway in balancing the vegetative development and freezing response in Arabidopsis. [ABSTRACT FROM AUTHOR]

Background: Anteromedial cortical support apposition (positive and/or neutral cortical relations) is crucial for surgical stability reconstruction in the treatment of trochanteric femur fractures. However, the loss of fracture reduction is frequent in follow-ups after cephalomedullary nail fixation. This paper aimed to investigate the possible predictive risk factors for postoperative loss of anteromedial cortex buttress after nail fixation. Methods: A retrospective analysis of 122 patients with AO/OTA 31A1 and A2 trochanteric femur fractures treated with cephalomedullary nails between January 2017 and December 2019 was performed. The patients were classified into two groups according to the postoperative status of the anteromedial cortical apposition in 3D CT images: Group 1 with contact "yes" (positive or anatomic) and Group 2 with contact "No" (negative, loss of contact). The fracture reduction quality score, tip-apex distance (TAD), calcar-referenced TAD (Cal-TAD), Parker ratio, neck-shaft angle (NSA), and the filling ratio of the distal nail segment to medullary canal diameter in anteroposterior (AP) and lateral fluoroscopies (taken immediately after the operation) were examined in univariate and multivariate analyses. Mechanical complications were measured and compared in follow-up radiographs. Results: According to the postoperative 3D CT, 84 individuals (69%) were categorized into Group 1, and 38 individuals (31%) were classified as Group 2. The multivariate logistic regression analysis showed that the poor fracture reduction quality score (P < 0.001) and decreasing filling ratio in the lateral view (P < 0.001) were significant risk factors for the loss of anteromedial cortical contact. The threshold value for the distal nail filling ratio in lateral fluoroscopy predicting fracture reduction re-displacement was found to be 53%, with 89.3% sensitivity and 78.9% specificity. The mechanical complication (varus and over lateral sliding) rate was higher in Group 2. Conclusions: The fracture reduction quality score and the decreasing filling ratio of the distal nail to the medullary canal in the lateral view (a novel parameter causing pendulum-like movement of the nail) were possible risk factors for postoperative loss of anteromedial cortical support. [ABSTRACT FROM AUTHOR]

The single Bi 4-x Eu x Ti 3 O 12 and Ni 1-x Cu x Fe 2 O 4 films were prepared via spin-coating method. The composite films of the Bi 3.4 Eu 0.6 Ti 3 O 12 /Ni 0.7 Cu 0.3 Fe 2 O 4 , annealed under N 2 , air and O 2 , were also prepared via the same method. Compared with the films of Bi 4 Ti 3 O 12 , the films of the Eu-doped Bi 4 Ti 3 O 12 (Bi 4-x Eu x Ti 3 O 12) exhibit enhanced ferroelectricity. And when x is equal to 0.6, the films of Bi 4-x Eu x Ti 3 O 12 show optimal ferroelectricity. Compared with the undoped NiFe 2 O 4 film, in the films of Ni 1-x Cu x Fe 2 O 4 , the doping of Cu2+ enhances ferromagnetism. And when x is equal to 0.3, the Ni 1-x Cu x Fe 2 O 4 films exhibit optimal ferromagnetism. For the composite films of Bi 3.4 Eu 0.6 Ti 3 O 12 /Ni 0.7 Cu 0.3 Fe 2 O 4 , annealing atmosphere has a significant impact on the magnetoelectric properties. In comparison with the composite films annealed under N 2 and air, the composite films annealed under O 2 exhibit optimum ferroelectricity (saturation polarization being 26.3 μC·cm−2), ferromagnetism (saturation magnetization being 385.6 emu·cm−3) and enhanced magnetoelectric coupling effect (magnetoelectric voltage coefficient being 86.4 mV·(cm·Oe)−1). This is beneficial for the applications in magnetoelectric functional devices. [ABSTRACT FROM AUTHOR]

Internet users' comments in online spaces have attracted researchers' attention in recent years. Although this data is typically publicly available, its use requires careful consideration so as to not cause harm to the users, while complying with the terms and conditions (Ts & Cs) of the online spaces. However, the Ts & Cs and researchers' ethical considerations may sometimes be in conflict. I faced such a conflict when I conducted discourse analysis of online discussions that were sourced from a public online learning platform owned by a private company. In this article, I reflect on how I navigated the Ts & Cs and copyright law, taking users' likely expectations into consideration when deciding whether to seek informed consent and anonymize content. I employed an 'attribution with anonymization' method to acknowledge users for their comments while safeguarding their confidentiality. Given the variety of online spaces and research methods, ethical decision-making must be a contextualized process that requires researchers to consider the nature of the online platform and the potential experience of the users, rather than simply following guidelines or Ts & Cs. [ABSTRACT FROM AUTHOR]

Background: In this study, we tried to access the efficacy and safety of oxaliplatin plus S-1 with intraperitoneal paclitaxel (PTX) for the treatment of Chinese advanced gastric cancer with peritoneal metastases.Patients and Methods: Thirty patients diagnosed with advanced gastric cancer underwent laparoscopic exploration and were enrolled when macroscopic disseminated metastases (P1) were confirmed. PTX was diluted in 1 l of normal saline and IP administered through peritoneal port at an initial dose of 40 mg/m2 over 1 h on day1,8, respectively. Oxaliplatin was administered intravenously at an initial dose of 100 mg/m2 on day1, and S-1 was administered orally at an initial dose of 80 mg/m2 for 14 days followed by 7 days rest, repeated by every 3 weeks.Results: Of all these 30 patients, the median number of cycles was 6 (range 2-16) due to the limitation of hematotoxicity and peripheral neuropathy by oxaliplatin. There were 11 (36.7%) patients received conversion surgery. The median progression free survival (PFS) was 6.6 months (95% CI = 4.7-8.5 months) and the median overall survival (OS) was 15.1 months (95% CI = 12.4-17.8 months). The grade 3-4 hematological toxicities were leucopenia (23.3%), neutropenia (23.3%), anemia (16.7%), and thrombocytopenia (20%), respectively. The grade 3-4 non-hematological toxicities were tolerated, most of which were peripheral sensory neuropathy (40%) due to oxaliplatin, diarrhea (20%), nausea and vomiting (26.7%).Conclusions: SOX+ip PTX regimen was effective in advanced gastric cancer with peritoneal metastasis. Survival time was significantly prolonged by conversion surgery. Grade 3-4 toxicities were uncommon. Large scale clinical trial is necessary to get more evidence to identify its efficacy.Trail Registration: ChiCTR, ChiCTR-IIR-16009802 . Registered 9 November 2016. [ABSTRACT FROM AUTHOR]

Background: We examined for the first time the imaging characteristics of Holmes tremor (HT) through multimodal 3D medical imaging.Case Presentation: Three patients with Holmes tremor who visited the Affiliated Hospital of Chengdu University of TCM from August 2018 to April 2021 were retrospectively investigated to summarize their clinical and imaging data.Results: Holmes tremor in two of the three patients was caused by hypertensive cerebral hemorrhage and in the third patient induced by hemorrhage due to ruptured brain arteriovenous malformations. HT occurred 1 to 24 months after the primary disease onset and manifested as a tremor in the contralateral limb, mostly in the upper portion. Cranial MRI showed that the lesions involved the thalamus in all three patients. The damaged thalamic nuclei included the ventral anterior nucleus, ventral lateral nucleus and ventromedial lateral nucleus, and the damaged nerve fibers included left thalamocortical tracts in one patient. In the other two patients, the damaged thalamic nuclei included the centromedian and dorsomedial nucleus, and the damaged nerve fibers included left cerebellothalamic and thalamocortical tracts. One patient showed significant improvement after treatment with pramipexole while the other two patients exhibited a poor response, one of whom had no response to the treatment with pramipexole and was only significantly relieved by clonazepam.Conclusion: We used multimodal 3D medical imaging for the first time to analyze the pathogenesis of HT and found that multiple thalamic nuclei were damaged. The damaged nuclei and nerve fiber tracts of two patients were different from those of the third patient, with different clinical manifestations and therapeutic effects. Therefore, it is speculated that there may be multiple pathogeneses for HT. [ABSTRACT FROM AUTHOR]

RNAi is an effective tool for gene function analysis and a promising strategy to provide environmentally friendly control approaches for pathogens and pests. Recent studies support the utility of bacterium-mediated RNAi as a cost-effective method for gene function study and a suitable externally applied delivery mechanism for pest control. Here, we developed a bacterium-mediated RNAi system in Spodoptera frugiperda based on four target genes, specifically, Chitinase (Sf -CHI), Chitin synthase B (Sf -CHSB), Sugar transporter SWEET1 (Sf -ST), and Hemolin (Sf -HEM). RNAi conducted by feeding larvae with bacteria expressing dsRNAs of target genes or injecting pupae and adults with bacterially synthesized dsRNA induced silencing of target genes and resulted in significant negative effects on growth and survival of S. frugiperda. However, RNAi efficiency and effects were variable among different target genes and dsRNA delivery methods. Injection of pupae with dsCHI and dsCHSB induced a significant increase in wing malformation in adults, suggesting that precise regulation of chitin digestion and synthesis is crucial during wing formation. Injection of female moths with dsHEM resulted in lower mating, fecundity, and egg hatching, signifying a critical role of Sf -HEM in the process of egg production and/or embryo development. Our collective results demonstrate that bacterium-mediated RNAi presents an alternative technique for gene function study in S. frugiperda and a potentially effective strategy for control of this pest, and that Sf -CHI, Sf -CHSB, Sf -ST, and Sf -HEM encoding genes can be potent targets. [ABSTRACT FROM AUTHOR]

A fractional-order model is proposed to describe the dynamic behaviors of the velocity of blood flow in cerebral aneurysm at the circle of Willis. The fractional-order derivative is used to model the blood flow damping term that features the viscoelasticity of the blood flow behaving between viscosity and elasticity, unlike the existing fractional models that use fractional-order derivatives to replace the integer-order derivatives as mathematical/logical generalization. A numerical analysis of the nonlinear dynamic behaviors of the model is carried out, and the influence of the damping term and the external power supply on the nonlinear dynamics of the model is investigated. It shows that not only chaos via period-doubling bifurcation is observed, but also two additional small period-doubling-bifurcation-like diagrams isolated from the big one are observed, a phenomenon that needs further investigation. [ABSTRACT FROM AUTHOR]

Sleep is the most important physiological process related to human health. The development of society has accelerated the pace of people's lives and has also increased people's life pressure. As a result, more and more people suffer from reduced sleep quality, and the resulting diseases are also increasing. In response to this problem, this study proposes a sleep quality detection and management method based on electroencephalogram (EEG). The detection of sleep quality is mainly achieved by staging sleep EEG signals. First, wavelet packet decomposition (WPD) preprocesses the collected original EEG to extract the four rhythm waves of EEG. Second, the relative energy characteristics and nonlinear characteristics of each rhythm wave are extracted. The multisample entropy (MSE) values of different scales are calculated as the main features, and the rest are auxiliary features. Finally, the long short-term memory (LSTM) model is applied to classify the extracted sleep features, and the final result is obtained. Experiments were conducted in the MIT-BIH public database. The experimental results show that the method used in this article has a high accuracy rate for sleep quality detection. For the detected sleep quality data, the data are managed in combination with the mobile terminal software. Management is mainly embodied in two aspects. One is to query and display historical sleep quality data. The second is that when there are periodic abnormalities in the detected sleep quality data, the user will be reminded so that the user can respond in time to ensure physical fitness. [ABSTRACT FROM AUTHOR]