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COVID-19 analysis from medical imaging is an important task that has been intensively studied in the last years due to the spread of the COVID-19 pandemic. In fact, medical imaging has often been used as a complementary or main tool to recognize the infected persons. On the other hand, medical imaging has the ability to provide more details about COVID-19 infection, including its severity and spread, which makes it possible to evaluate the infection and follow-up the patient's state. CT scans are the most informative tool for COVID-19 infection, where the evaluation of COVID-19 infection is usually performed through infection segmentation. However, segmentation is a tedious task that requires much effort and time from expert radiologists. To deal with this limitation, an efficient framework for estimating COVID-19 infection as a regression task is proposed. The goal of the Per-COVID-19 challenge is to test the efficiency of modern deep learning methods on COVID-19 infection percentage estimation (CIPE) from CT scans. Participants had to develop an efficient deep learning approach that can learn from noisy data. In addition, participants had to cope with many challenges, including those related to COVID-19 infection complexity and crossdataset scenarios. This paper provides an overview of the COVID-19 infection percentage estimation challenge (Per-COVID-19) held at MIA-COVID-2022. Details of the competition data, challenges, and evaluation metrics are presented. The best performing approaches and their results are described and discussed. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), which is a prevailing type of dementia, presents a significant global health concern. The current therapies do not meet clinical expectations. Amyloid-beta (Aβ) has been found to induce endogenous formaldehyde (FA) accumulation by inactivating FA dehydrogenase (FDH); in turn, excessive FA triggers Aβ aggregation that eventually leads to AD onset. Hence, scavenging FA by astaxanthin (ATX, a strong exogenous antioxidant) may be pursued as a promising disease-modifying approach. Here, we report that liposomal nanoparticles coupled with PEG (PEG-ATX@NPs) could enhance water-solubility of ATX and alleviate cognitive impairments by scavenging FA and reducing Aβ deposition. To enable drug delivery to the brain, liposomes were used to encapsulate ATX and then coupled with PEG, which produced liposomal nanoparticles (PEGATX@NPs) with a diameter of <100 nm. The PEG-ATX@NPs reduced Aβ neurotoxicity by both degrading FA and reducing FA-induced Aβ assembly in vitro. Intraperitoneal administration of PEG-ATX@NPs in APPswe/PS1dE9 mice (APP/PS1, a familial model of AD), not only decreased the levels of brain FA and malondialdehyde (MDA, a typical product of oxidative stress), but also attenuated both intracellular Aβ oligomerization and extracellular Aβ-related senile plaque (SP) formation. These pathological changes were accompanied by rescued ability of spatial learning and memory. Collectively, PEG-ATX@NPs improved the water-solubility, bioavailability, and effectiveness of ATX. Thus, it has the potential to be developed as a safe and effective strategy for treating AD. [Display omitted] • Liposomal NPs of ATX with PEG enhances its bioavailability and drug delivery. • Scavenging FA by PEG-ATX@NPs decreases Aβ oligomerization and deposition. • PEG-ATX@NPs more than ATX reduce Aβ neurotoxicity by scavenging FA. • PEG-ATX@NPs may be a promising strategy for treating Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Spintronics and condensed matter physics are in pursuit of materials that can serve as carriers for novel quantum devices. Antiferromagnetic rare earth orthoferrites (R FeO 3 , where R is rare earth or Y), are potential functional materials for magnetic information processing. They exhibit temperature-controlled spin reorientation transition (SRT) and magnetic field/temperature-induced spin switching (SSW) properties. As such, R FeO 3 is expected to be used in spintronic devices that can easily control the spin. With the advancement of research, the co-doping of rare earth ions has emerged as a prominent area of investigation in R FeO 3. In this work, we have grown a series of Tm 1- x Sm x FeO 3 (TSFO, x = 0, 0.2, 0.3, 0.4) single crystals via a four-mirror optical floating zone furnace. Crystal axes and single phase of these single crystals were determined using Laue back reflection camera and X-ray diffractometer. We observed that the doping of Sm ions can effectively regulate the spin reorientation temperature of the parent material TmFeO 3. Both type-I and type-II SSW have been observed when the doping rate x is 0.2 or 0.4, perfectly integrating the magnetic properties of TmFeO 3 and SmFeO 3 single crystals. Furthermore, the spin switching in TSFO (x = 0.2, 0.3, 0.4) can be manipulated by applying low magnetic fields with tens of Oe. On the other hand, when the doping rate x reaches 0.4, the magnetic compensation phenomenon and the Néer temperature of rare earth ions occurred. The super-exchange interaction between R 3+ and Fe3+ magnetic sublattices leads to these interesting phenomena. [ABSTRACT FROM AUTHOR]

Introduction: The synergistic impact of coexistent malnutrition and sarcopenia on morality in hospitalized patients with decompensated cirrhosis remains elusive. This prospective cohort study aimed to delineate the prevalence concerning coexistence of malnutrition and sarcopenia and the prognosticating role on long-term mortality among cirrhosis. Methods: Adult cirrhotic patients with decompensated episodes between 2019 and 2021 were consecutively enrolled. Malnutrition and sarcopenia were diagnosed according to the Global Leadership Initiative on Malnutrition (GLIM) criteria and the European Working Group on Sarcopenia in Older People (EWGSOP2) algorithm, respectively. The entire cohort was divided into three groups: non-malnutrition and non-sarcopenia (NN), malnutrition or sarcopenia, and coexistent malnutrition and sarcopenia (MS). Log-rank test and multivariate Cox regression model were utilized to evaluate survival status and independent risk factors for mortality, respectively. Results: Our findings indicated that malnutrition manifested in 44.6% of inpatients with decompensated cirrhosis, while sarcopenia presented in 16.4% of the entire cohort, indicative of a prevalence of 14.7% regarding coexistent malnutrition and sarcopenia. The Kaplan-Meier graphic demonstrated a significant difference regarding survival curves among the three groups, referring to the MS group presented with the lowest survival rate (log-rank test: p < 0.001). Moreover, coexistent malnutrition and sarcopenia were associated with nearly 4 times higher mortality risk (model 1: hazard ratio [HR] = 3.31, 95% confidence interval [CI]: 1.20–9.13, p = 0.020; model 2: HR = 4.34, 95% CI: 1.52–12.4, p = 0.006) in comparison with patients without any condition (NN group). Conclusions: Malnutrition and sarcopenia had superimposed negative impacts on inpatients with decompensated cirrhosis. It is imperative to identify this vulnerable subset to provide prompt therapeutic intervention for better prognosis. [ABSTRACT FROM AUTHOR]

High quality TmFeO 3 single crystal with the length of 50 mm has been prepared by using a four-mirror optical floating zone furnace. X-ray diffractometer and Laue back reflection camera are used to determine the quality and crystal orientations of TmFeO 3 single crystal. Here, the magnetic properties of TmFeO 3 single crystal in low magnetic fields are studied systematically. A typical spin reorientation transition from Γ 4 (G x , A y , F z) configuration to Γ 2 (F x , C y , G z) configuration is observed in TmFeO 3 single crystal with the temperature between 82 K and 95 K. Temperature-induced type-II spin switching in both a -axis and c -axis are observed in field cooling and measuring while cooling (FCC) and field cooled and measuring while warming (FCW) modes, which has not been reported in previous researches on TmFeO 3 single crystal. This is an extremely rare occurrence within the R FeO 3 family. The results suggest that such spin switching is easily susceptible to very low external magnetic fields. Therefore, by adjusting the magnitude of the external magnetic fields, the triggering temperatures of spin switching can be controlled, which offers the possibility of the application for TmFeO 3 single crystal in future spintronic devices. [ABSTRACT FROM AUTHOR]

Cuticle wax chemicals are cultivar-dependent and contribute to storage quality. Few research reported on wax analysis between melting flesh-type (MF; 'Jinhuami 25') and nonmelting flesh-type (NMF; 'Xizhoumi 17' and 'Chougua') Hami melons. Chemicals and crystal structures of Hami melon cuticular wax, cell wall metabolism related to fruit melting, and fruit physiology were analyzed to observe wax functions. Results showed that Hami melon cuticle wax predominantly consists of esters, alkanes, alcohols, aldehydes, and terpenoids. MF-type has a lower alkane/terpenoid ratio, concomitant to its higher weight loss and cuticle permeability. Micromorphology of wax crystals appears as numerous platelets with irregular crystals, and the transformation of wax structure in NMF Hami melon is delayed. Waxy components affect cell wall metabolism and physiological quality, which results in the pulp texture difference between MF-type and NMF-type during storage. Results provide a reference for the regulation of wax synthesis in both types of melons. [Display omitted] • Changes in cuticular wax composition are related to softening of Hami melon fruit. • Weight loss and cuticle permeability is correlated with alkane/terpenoid ratio. • Changes in wax composition affect cell wall metabolism and physiological quality. • Wax composition causes differences in pulp texture between MF and NMF-type fruit. • The loss of flake crystals in 'Jinhuami 25' wax is due to increased ester content. [ABSTRACT FROM AUTHOR]

Introduction: Nonspecific chronic low back pain (NCLBP) is a leading contributor to disease burden worldwide, and the management of NCLBP has always been a problem. This study is designed to explore the feasibility and efficacy of m-health-based core stability exercise (CSE) combined with self-compassion training (SCT) and compare it with m-health-based CSE alone for the management of NCLBP. Methods: This study is a pilot, patient-blinded randomized controlled trial. Participants with NCLBP were randomized into an intervention group and a control group. All the participants received m-health-based CSE, but those in the intervention group also received SCT before CSE. The intervention took place weekly on Saturday or Sunday for 4 weeks in total. Patients self-assessed their outcomes by filling out electronic questionnaires at 4 and 16 weeks after the start of the study. The primary outcome metrics for these questionnaires were back pain disability (based on the Roland–Morris Disability Questionnaire, RMDQ) and Pain intensity (Numeric Rating Scale, NRS; current pain, worst pain, average pain). The secondary outcome metrics were anxiety (GAD-7,7-item Generalized Anxiety Disorder scale), Depression Symptoms (PHQ-9,Patient Health Questionnaire-9), pain catastrophizing (PCS, Pain Catastrophizing Scale) and Self-efficiency (PSEQ, Pain Self-Efficiency Questionnaire). Results: A total of 37 patients comprising 28 (75.7%) females completed the study, with 19 patients in the intervention group and 18 in the control group. The mean (SD) patient age was 35.2 (11.1) years. For all primary outcomes, although there were no significant differences between groups, we found that participants in the intervention group improved function and pain earlier. The RMDQ score changed by − 1.771 points (95% CI − 3.768 to 0.227) from baseline to 4 weeks in the control group and by − 4.822 points (95% CI − 6.752 to − 2.892) in the intervention group (difference between groups, − 3.052 [95% CI − 5.836 to − 0.267]). Also, the RMDQ score changed by − 3.328 points (95% CI − 5.252 to − 1.403) from baseline to 16 weeks in the control group and by − 5.124 points (95% CI − 7.014 to − 3.233) in the intervention group (difference between groups − 1.796 [95% CI − 4.501 to 0.909]). A similar pattern was found in the NRS scores. For secondary outcomes, the intervention group was superior to the control group in for GAD-7 (intervention difference from CSE along at week 16, − 2.156 [95% CI − 4.434 to − 0.122; P value for group effect was 0.030]). At the end of treatment, the improvement in PCS in the intervention group was significant (difference in PCS score at week 4, − 6.718 [95% CI − 11.872 to − 1.564]). We also found significant changes in PCS in the control group (− 6.326 [95% CI, − 11.250 to − 1.401]) at the 16-week follow-up. As for PSEQ, there were no apparent differences between the two groups. There were no adverse events relented to study participation. Conclusions: The pilot study is feasible to deliver, and our results indicate that participants in the group of m-health-based CSE combined with SCT may experience faster relief from pain intensity and back disability than those in the group of m-health-based CSE alone. Trial Registration: ChiCTR2100042810. Plain Language Summary: The impact of chronic low back pain on people's life quality and social economy is increasing year by year. Helping patients self-manage low back pain through a biological-psycho-social model seems to be an effective management approach, but the lack of connectivity between disciplines limits the development of multidisciplinary collaboration. Mindfulness-related therapy (self-compassion training) has been proven to be effective in chronic pain, and exercise therapy is widely used in rehabilitation medicine. In this study, these two programs were combined. We also used mobile health technology in the study, which brings a lot of convenience for research. The results of the study showed that the efficacy of the combined group seemed to be more obvious and worthy of further study. [ABSTRACT FROM AUTHOR]

Oil-based emulsions are commonly formulations in agricultural spraying but their spray break-up behaviour and droplet characteristics differ from those when water is sprayed. In this paper, the effect of spray structure on the droplet characteristics, droplet size distribution and droplet velocity, were investigated using the high-speed photomicrography and image processing. Formation of the typical spray structure and the effect of emulsion concentration and spray pressure on the spray structure and droplets characteristics were analysed. Results show that the use of oil-based emulsion decreases the liquid sheet area and the flapping form of break-up when compared to water sprays and it is this change that is responsible for the increase of droplet size. Thus, oil-based emulsion sprays have a narrower droplet size distribution due to the limited amount of liquid sheet flapping and the subsequent changes break-up structure. The decrease of flapping increases the velocity of the droplets in oil-based emulsion spray by 43% compared with the water spray. Emulsion sprays typically have both flapping and perforating break-up mechanisms when the emulsion concentration is low and the spray pressure is high. The results in this paper indicate that the perforating break-up mechanism can dominate the flapping mechanism when spray pressure is < 0.3 MPa and the emulsion concentration >0.1%. • Quantitative information of liquid sheet is obtained via image processing methods. • The effects of break-up structure on the droplet characteristics are investigated. • A hypothesis on the formation of spray structure of emulsion and water is proposed. • A competition arises between flapping and perforation mechanisms in emulsion spray. • The competition is influenced by the spray pressure and the emulsion concentration. [ABSTRACT FROM AUTHOR]

• NFTS had the best effect on storage quality compared to low and room temperatures. • Near-freezing temperature storage (NFTS) delayed senescence in P. domestica fruit. • NFTS reduced ROS accumulation and enhanced antioxidant enzymes activity. • NFTS is effective for maintaining P. domestica fruit quality during storage. P. domestica fruit are highly perishable due to its intense metabolic activity. To increase the storage time while preserving the quality, the effects of postharvest storage at near-freezing temperature (NFTS) (−1 to −1.5 °C) on the physiological indexes and antioxidant enzyme activities of P. domestica fruit were investigated. The results showed that the weight loss rate (4.04 %), soluble solid content (1.08 %), color difference (18.27 %), respiration rate (23.90 %), anthocyanin content (41.13 %), malondialdehyde content (5.39 %), hydrogen peroxide content (13.32 %), and superoxide anion activity (13.97 %) of P. domestica fruit in the NFTS group were reduced, but the firmness (4.95 %), ascorbic acid content (31.71 %), total phenol content (2.54 %), and the activities of superoxide dismutase (SOD, 4.67 %), catalase (CAT, 168.92 %), ascorbate peroxidase (APX, 127.17 %), and peroxidase (POD, 34.54 %) were increased, compared with the room temperature (25 °C) group. Therefore, NFTS could effectively preserve the quality of harvested P. domestica fruit, improve the antioxidant properties, and delay the senescence. This study proposed that NFTS could be used as a promising storage technique to reduce postharvest oxidative stress. [ABSTRACT FROM AUTHOR]

• The proposed method improves the production efficiency of the machine. • The reliability and superiority of the proposed method are verified by simulation. • The proposed method in this paper is able to achieve the optimal solution. In an automated stereoscopic warehouse, the efficiency of the Rail Guided Vehicle (RGV) is the bottleneck. This paper proposes a foresight stepping model to optimize the intelligent RGV scheduling scheme. We incorporate the chaotic particle swarm optimization algorithm into the model and design the mechanism of multi-step processing. The machine optimization is used to compare the optimal alignment effect of the Back Propagation (BP) network algorithm and GradientBoostingDecisionTree (GBDT) algorithm. The real-life system test is performed by simulation. The simulation results show that the GBDT-foresight stepping model is superior to the traditional models in terms of complexity, reliability and accuracy. Image, graphical abstract The problem addressed in this paper is the work optimization problem in a workshop. [ABSTRACT FROM AUTHOR]

Radio-immunotherapy has offered emerging opportunities to treat invasive melanoma due to its immunostimulatory performances to activate antitumor immune responses. However, the immunosuppressive microenvironment and insufficient response rate significantly limit the practical efficacy. This study presents an autologous cell-derived exosomes (Exo)-engineered nanoagonist (MnExo@cGAMP) containing with metalloimmunotherapeutic agent (Mn 2+ ions) and nucleotidyltransferase (2',3'-cGAMP, a STING agonist) for boosting melanoma-targeted radio-immunotherapy by cascade cGAS-STING pathway activation. The MnExo@cGAMP can efficiently accumulate in tumor cells due to the autologous targeting performance. Once internalized by tumor cells, the released Mn 2+ ions will enhance stimulator of interferon gene (STING) binding and sensitize cyclic GMP-AMP (cGAS) to radiotherapy-induced double-straned DNA (dsNDA), resulting in amplification of cGAS-STING pathway activation together with X-ray irradiation. Meanwhile, loaded 2',3'-cGAMP can directly augment pathway activity acting as a secondary messenger. These cascade activations of cGAS-STING pathway trigger the overexpression of type I interferon, promote dendritic cells (DCs) maturation, antigen presentation, and increase CD8 + T cell activation, resulting effective radio-immunotherapeutic outcome by overcoming immune-suppression in melanoma. This study demonstrates a targeted therapeutic modality involving metalloimmunotherapy and agonist for efficient melanoma radio-immunotherapy by cascade cGAS-STING pathway activation., (© 2024 Wiley‐VCH GmbH.)

Background: The protein p53, encoded by the most frequently mutated gene TP53 in human cancers, has diverse functions in tumor suppression. As a best known transcription factor, p53 can regulate various fundamental cellular responses, ranging from the cell-cycle arrest, DNA repair, senescence to the programmed cell death (PCD), which includes autophagy, apoptosis, ferroptosis, cuproptosis, pyroptosis and disulfidoptosis. Accumulating evidence has indicated that the tumor microenvironment (TME), N 6 -methyladenosine (m 6 A) modification and diverse PCD are important for the progression, proliferation and metastases of cancers., Aim of Review: This paper aims to systematically and comprehensively summarize the multiple roles of p53 in the development of cancers from the regulation of TME, m 6 A Modification and diverse PCD., Key Scientific Concepts of Review: TME, a crucial local homeostasis environment, influences every step of tumorigenesis and metastasis. m 6 A, the most prevalent and abundant endogenous modification in eukaryotic RNAs, plays an essential role in various biological processes, containing the progression of cancers. Additionally, PCD is an evolutionarily conserved mechanism of cell suicide and a common process in living organisms. Some forms of PCD contribute to the occurrence and development of cancer. However, the complex roles of p53 within the TME, m 6 A modification and diverse PCD mechanisms are still not completely understood. Presently, the function roles of p53 including the wild-type and mutant p53 in different context are summarized. Additionally, the interaction between the cancer immunity, cancer cell death and RNA m 6 A methylation and the p53 regulation during the development and progress of cancers were discussed. Moreover, the key molecular mechanisms by which p53 participates in the regulation of TME, m 6 A and diverse PCD are also explored. All the findings will facilitate the development of novel therapeutic approaches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Exogenous gaseous formaldehyde (FA) is recognized as a significant indoor air pollutant due to its chemical reactivity and documented mutagenic and carcinogenic properties, particularly in its capacity to damage DNA and impact human health. Despite increasing attention on the adverse effects of exogenous FA on human health, the potential detrimental effects of endogenous FA in the brain have been largely neglected in current research. Endogenous FA have been observed to accumulate in the aging brain due to dysregulation in the expression and activity of enzymes involved in FA metabolism. Surprisingly, excessive FA have been implicated in the development of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and brain cancers. Notably, FA has the ability to not only initiate DNA double strand breaks but also induce the formation of crosslinks of DNA-DNA, DNA-RNA, and DNA-protein, which further exacerbate the progression of these brain diseases. However, recent research has identified that FA-resistant gene exonuclease-1 (EXO1) and FA scavengers can potentially mitigate FA toxicity, offering a promising strategy for mitigating or repairing FA-induced DNA damage. The present review offers novel insights into the impact of FA metabolism on brain ageing and the contribution of FA-damaged DNA to the progression of neurological disorders., (© 2024. The Author(s).)

The postharvest quality of winter jujubes is prone to deterioration, including inevitable pericarp reddening and rapid nutrient loss from the flesh, significantly impacting its edible quality and commercial value. As a crucial metabolic pathway in plants, phenylpropane metabolism not only regulates plant stress resistance but also closely relates to various coloration effects. In this study, we investigated the effects of luteolin solutions on postharvest color changes and phenylpropanoid metabolism in winter jujube. The results indicated that compared to the control group, winter jujube fruit treated with 200 mg L -1 luteolin exhibited improved quality indexes, increased antioxidant capacity (capability of eliminating ABTS and DPPH radicals), and higher activities of antioxidant enzymes(superoxide dismutase (SOD), and catalase (CAT)). This led to a reduction in the oxidation of phenolic substances in winter jujube. Furthermore, luteolin treatment inhibited phenylpropanoid metabolism by suppressing the activities of 4-Coumarate: coenzyme A ligase (4CL), phenylalanine ammonilyase (PAL), and cinnamate 4 hydroxylase (C4H), as well as the expression of ZjUFGT, ZjDFT, and ZjPAL genes. Consequently, anthocyanin and quercetin synthesis were limited while the degradation rate of chlorophyll and carotenoid synthesis were slowed down after luteolin treatment. This resulted in delayed reddening of winter jujube following luteolin treatment. In conclusion, luteolin exhibits potential application prospects as a preservative for inhibiting reddening and browning in winter jujubes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background/objectives: Malnutrition coexisting with abdominal adipose tissue accumulation bring a double burden on prognosis. More recently, the Global Leadership Initiative on Malnutrition (GLIM) has reached a novel consensus concerning the diagnostic criteria, that is, a two-step modality combining nutritional risk screening and subsequent phenotypic/etiologic parameters for comprehensive evaluation in hopes of harmonizing the malnutrition diagnosis. We aimed to elucidate their synergistic impact among inpatients with decompensated cirrhosis concerning long-term mortality., Subjects/methods: Malnutrition, visceral obesity, and visceral adiposity were defined by the Global Leadership Initiative on Malnutrition (GLIM), visceral fat area (VFA), and visceral to subcutaneous adipose tissue area ratio (VSR) on computed tomography, respectively. Accordingly, the patients were categorized into different groups given their nutritional status and visceral obesity/adiposity. Multivariate Cox regression was performed to identify independent risk factors associated with 1-year all-cause mortality. Kaplan-Meier curves with log-rank tests were compared among distinct groups., Results: Totally, 295 patients were recruited. GLIM, VFA, and VSR identified 131 (44.4%), 158 (53.6%), and 59 (20%) patients with malnutrition, visceral obesity and visceral adiposity, respectively. Malnutrition coexisted with visceral obesity in 55 (MO group) relative to visceral adiposity in 40 patients (MA group). Multivariate Cox analysis showed that MA (hazard ratio: 2.48; 95% confidence interval: 1.06, 5.79; P = 0.036) was independently associated with dire outcome rather than MO. Moreover, patients with cirrhosis in the MA group had the worst survival status when compared with other groups (log-rank test: P < 0.001)., Conclusions: The current study indicated that coexisting GLIM-defined malnutrition and VSR-defined visceral adiposity were in relation to worse long-term mortality among inpatients. It is imperative to delicately manage nutritional status and provide personalized treatment in this vulnerable subgroup for achieving better prognosis., (© 2024. The Author(s).)

We sought to develop and validate a machine learning (ML) model for predicting multidimensional frailty based on clinical and laboratory data. Moreover, an explainable ML model utilizing SHapley Additive exPlanations (SHAP) was constructed. This study enrolled 622 patients hospitalized due to decompensating episodes at a tertiary hospital. The cohort data were randomly divided into training and test sets. External validation was carried out using 131 patients from other tertiary hospitals. The frail phenotype was defined according to a self-reported questionnaire (Frailty Index). The area under the receiver operating characteristics curve was adopted to compare the performance of five ML models. The importance of the features and interpretation of the ML models were determined using the SHAP method. The proportions of cirrhotic patients with nonfrail and frail phenotypes in combined training and test sets were 87.8% and 12.2%, respectively, while they were 88.5% and 11.5% in the external validation dataset. Five ML algorithms were used, and the random forest (RF) model exhibited substantially predictive performance. Regarding the external validation, the RF algorithm outperformed other ML models. Moreover, the SHAP method demonstrated that neutrophil-to-lymphocyte ratio, age, lymphocyte-to-monocyte ratio, ascites, and albumin served as the most important predictors for frailty. At the patient level, the SHAP force plot and decision plot exhibited a clinically meaningful explanation of the RF algorithm. We constructed an ML model (RF) providing accurate prediction of frail phenotype in decompensated cirrhosis. The explainability and generalizability may foster clinicians to understand contributors to this physiologically vulnerable situation and tailor interventions., (© The Author(s) 2024. Published by Oxford University Press.)

Background: There is a paucity of data regarding sex-oriented analyses of connection between muscle quantity and quality and health-related quality of life (HRQoL), taking into account the pathophysiological differences of sarcopenia/myosteatosis in males versus females. We sought to investigate the associations between skeletal muscle index (SMI)-defined sarcopenia and intramuscular adipose tissue content (IMAC)-defined myosteatosis and EuroQol-5D (EQ-5D)-defined HRQoL in patients with decompensated cirrhosis concerning sex disparities., Methods: Totally, 382 patients were enrolled. The relationship between SMI/IMAC and HRQoL was evaluated with restricted cubic spline and Pearson correlation analyses. Furthermore, association between SMI or sarcopenia and EQ-5D utility index was determined by multiple linear regression, adjusted for age, BMI and concurrent disease severity., Results: The study population comprised evenly distributed male and female patients (190: 192), mean age 61.9 years. The prevalence of sarcopenia (40.5 versus 9.9%, P < 0.001) and SMI (48.8 versus 42.2 cm 2 /m 2 , P < 0.001) were significantly higher in males relative to females, with comparable myosteatosis prevalence (15.3 versus 16.7%, P = 0.708). Self-care, usual activities and pain within EQ-5D scale were more prevalent in the sarcopenia compared with non-sarcopenia groups across entire population and stratified by sex. The SMI values exhibited a significantly linear correlation with EQ-5D utility index in male but not female patients (P for non-linearity = 0.281). In multiple analysis, SMI or the presence of sarcopenia was both significantly associated with EQ-5D utility index. Subgroup analyses unveiled no discernible interactions between sarcopenia and EQ-5D utility index., Conclusions: Muscle quantity measured by SMI was associated with declined HRQoL in males rather than females, whereas no associations were found regarding muscle quality measured by IMAC in both sexes. It is tempting to manage sarcopenia by increasing SMI levels as high as possible in hopes of achieving better health consequence. Our findings represent the importance of connecting CT-demarcated body composition abnormalities to meaningful patient-centered outcomes. Future targeted studies with sizable multi-center populations are warranted to clarify this causality, and in consequence develop optimized intervention against sarcopenia/myosteatosis or key determinants concerning impaired HRQoL., (© 2024. The Author(s).)

The potential of salicylic acid (SA) in delaying postharvest fruit senescence has been extensively documented; nevertheless, its effect on antioxidant activity and quality of 'France' prune fruit is largely unknown. The study investigated the effects of SA (0.5 mM) on postharvest quality deterioration of 'France' prune fruit. Results indicated that SA impeded the increase in respiration rate and weight loss, and mitigated the decrease of soluble solids content (SSC), titratable acidity (TA) content, firmness, and hue angle. SA sustained the ascorbate-glutathione cycle by inducing the production of ascorbic acid (AsA) and glutathione (GSH) and attenuates flavonoids, total phenols, and anthocyanins degradation by inhibiting polyphenol oxidase (PPO) activity and PdPPO . Moreover, SA significantly improved superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), peroxidase (POD), and glutathione reductase (GR) activities and gene expression levels, sustained higher 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging capacity, ferric reducing antioxidant power (FRAP), and hydroxyl radical (·OH) inhibition capacity, and impeded the production of hydrogen peroxide (H 2 O 2 ) and superoxide anion (O 2 •- ). Overall, SA improved the antioxidant capacity by inducing the synthesis of defense response-related substances and promoting antioxidant enzyme activities to sustain the storage quality of 'France' prune fruit.

Rifaximin, derived from rifamycin, is a broad-spectrum antibiotic by inhibiting bacterial RNA synthesis. Rifaximin has a very low intestinal absorption and exerts its antimicrobial activity primarily in the intestinal tract. It regulates the gut microbiota with limited side effects systemically. Rifaximin has been recommended for the treatment of hepatic encephalopathy but some studies shed light on its medicinal effects in many other diseases. For instance, rifaximin may suppress the progression of liver fibrosis and its related complications, and ameliorate metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease, etc. Rifaximin can also mediate anti-inflammation, antiproliferation, and proapoptotic events by activating pregnane X receptor, which is efficious in cancers such as colon cancer. In addition, some investigations have shown rifaximin may play a therapeutic role in various autoimmune and neurological disorders. However, these findings still need more real-world practices and in-depth investigations to obtain more precise indications and fully elucidate the multifaceted potentials of rifaximin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Ultrasonic-assisted extraction using a natural deep eutectic solvent (UAE-NADES) is an efficient method for extracting grape seed polyphenols (GSPs). In this study, response surface methodology was used to optimize the extraction of GSPs with UAE-NADES, and the theoretical extraction rate of GSPs was 139.014 mg GAE/g, the actual extraction rate was 135.78 ± 1.3 mg GAE/g. A pseudo-second-order kinetic extraction fitting was established to simulate the extraction process and mechanism (R 2  > 0.99). Analysis of antioxidant capacity, Fourier-infrared spectroscopy and scanning electron microscopy revealed that UAE-NADES works synergetically to maintain the stability of extracted GSPs. The results of high-performance liquid chromatography showed that catechin (41.14 mg/g) is the main component of GSPs in the extract. The UAE-NADES extraction of GSPs can inhibit the growth of Alternaria alternata at 0.25 mg GAE/g, while the GSPs extracted by other methods can effectively inhibit the growth of Alternaria alternata at 0.35 mg GAE/g. Thus, this study demonstrates that UAE-NADES is a high-efficiency means of extracting GSPs and, in a wider sense, is a promising extraction technology for the green utilization of waste resources., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Magnetic refrigeration based on the magnetocaloric effect is gaining interest in orthogonal or hexagonal rare-earth manganite. However, a more comprehensive understanding of the underlying mechanism is still required. We grew a high-quality single crystal of Dy 0.5 Ho 0.5 MnO 3 using the optical floating zone method, since the parent crystals DyMnO 3 and HoMnO 3 have orthogonal and hexagonal structures, respectively. The magnetic and magnetocaloric properties and refrigeration mechanisms are thoroughly investigated. Doping modifies the magnetism according to the results obtained from the investigation of magnetic and dielectric properties and heat capacity. The spin reorientation transition shifts towards low temperature in comparison to HoMnO 3 . Near the Néel temperature of rare-earth sublattices (5 K), the highest changes in negative magnetic entropy under 0-70 kOe are 18 J kg -1 K -1 and 13 J kg -1 K -1 along the a - and c -axes, respectively. The low-temperature metamagnetic phase transition caused by the alterations in the magnetic symmetry of Ho 3+ contributes to an increased magnetocaloric effect in comparison to the parent crystals, rendering it a promising choice for magnetic refrigeration applications. Dy 0.5 Ho 0.5 MnO 3 exhibits a clear magnetocrystalline anisotropy with enhanced refrigeration capacity and negative magnetic entropy change along the a -axis. The adiabatic temperature change of Dy 0.5 Ho 0.5 MnO 3 is 8.5 K, larger than that of HoMnO 3 , rendering it a promising choice for low-temperature magnetic refrigeration applications.

Emerging evidence expands on a close connection between trace elements and muscular abnormalities, mostly focusing on sarcopenia. We hypothesized an association between concentrations of serum trace elements and myosteatosis, given that myosteatosis has a more pronounced clinical implication relative to sarcopenia, but there is a paucity of data in patients with cirrhosis. Consecutive patients were hospitalized for cirrhosis-associated complications. Serum trace elements (zinc, copper, manganese [Mn], magnesium, calcium, and iron) were measured by inductively coupled plasma mass spectrometry. The presence of myosteatosis was defined according to computed tomography-demarcated intramuscular adipose tissue content. In total, the 295 patients with cirrhosis analyzed had a median age of 63 years and 53.6% were male. Among them, 42 patients presented with myosteatosis (14.2%) and concomitant higher Model for End-stage Liver Disease-Sodium and triglyceride concentrations and lower neutrophil counts and serum Mn concentrations (all P < .05). No differences were found regarding other 5 trace elements in patients with versus without myosteatosis. The median serum Mn concentrations were 1.16 µg/L, and this population was categorized into high-Mn and low-Mn groups. The proportion of myosteatosis was significantly lower in high-Mn group than that in low-Mn group (8.1% vs 20.4%, P < .001). Univariable binary logistic regression indicated that low Mn was associated with myosteatosis (odds ratio, 2.906; 95% confidence interval, 1.424-5.932; P = .003) in the context of cirrhosis. This result was validated according to multivariable analysis by adjusting for confounding factors. In conclusion, low serum Mn can be predictive of myosteatosis, a novel muscular abnormality representing more clinical relevance and close relation to inferior outcomes among cirrhosis., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The current preoperative malignancy risk evaluation for thyroid nodules involves stepwise diagnostic modalities including ultrasonography, thyroid function serology and fine-needle aspiration (FNA) cytopathology, respectively. We aimed to substantiate the stepwise contributions of each diagnostic step and additionally investigate the diagnostic significance of quantitative chromogenic imprinted gene in-situ hybridization (QCIGISH)-an adjunctive molecular test based on epigenetic imprinting alterations., Methods: A total of 114 cytopathologically-diagnosed and histopathologically-confirmed thyroid nodules with complete ultrasonographic and serological examination records were evaluated using QCIGISH in the study. Logistic regression models for thyroid malignancy prediction were developed with the stepwise addition of each diagnostic modality and the contribution of each step evaluated in terms of discrimination performance and goodness-of-fit., Results: From the baseline model using ultrasonography [area under the receiver operating characteristics curve (AUROC): 0.79; 95% confidence interval (CI): 0.71-0.86], significant improvements in thyroid malignancy discrimination were observed with the stepwise addition of thyroid function serology (AUROC: 0.82; 95% CI: 0.74-0.90; P=0.23) and FNA cytopathology (AUROC: 0.88; 95% CI: 0.81-0.94; P=0.02), respectively. The inclusion of QCIGISH as an adjunctive molecular test further advanced the preceding model's diagnostic performance (AUROC: 0.95; 95% CI: 0.91-1.00, P=0.007)., Conclusions: Our study demonstrated the significant stepwise diagnostic contributions of standard clinical assessments in the malignancy risk stratification of thyroid nodules. However, the addition of molecular imprinting detection further enabled a more accurate and definitive preoperative evaluation especially for morphologically indeterminate thyroid nodules and cases with potentially discordant results among standard modalities.

Background and Objectives: There is limited evidence concerning the predictive value of health-related quality of life (HRQoL) on the presence of frailty in the context of cirrhosis. We aimed to elucidate the relationship between HRQoL and multidimensional frailty and to determine which HRQoL dimension independently impacted frail phenotype in our established cohort., Methods: This was a prospective observational study by consecutively enrolling 355 patients with cirrhotic with decompensated signs in China. The HRQoL and frail phenotype were evaluated by the EuroQol-5D (EQ-5D) Questionnaire and Frailty Index, respectively. The relationship between EQ-5D utility index, as well as respective EQ-5D dimension, and Frailty Index was analysed according to the multiple linear regression analyses., Results: More than half of the patients (56.3%) reported problems in any dimension of the EQ-5D, suggestive of impaired HRQoL. Moreover, the proportion of patients experiencing some/extreme problems significantly increased across all five dimensions (all p<0.001) in correspondence to transition from the robust to frail phenotype. Multiple linear regression analyses demonstrated that age, ascites and hepatic encephalopathy were positively associated with Frailty Index, while EQ-5D utility index (standardised β coefficient= -0.442, p<0.001) negatively associated with Frailty Index. Notably, usual activities, self-care and mobility were the most influencing predictors associated with frailty., Conclusions: Our results support a rapid HRQoL assessment via EQ-5D may assist in predicting multidimensional frailty, and usual activities, self-care and mobility tend to be remediable targets while taking their effect on frail phenotype into consideration among patients with cirrhosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To assess and compare the effectiveness of ultrasound-guided core needle biopsy (CNB) in comparison to repeat fine-needle aspiration(rFNA) for thyroid nodules that yield inconclusive results following the initial fine-needle aspiration (FNA)., Methods: A cohort of 471 patients who received an inconclusive cytological diagnosis following the initial FNA were included in this study. These patients subsequently underwent either CNB (n=242) or rFNA (n=229). The inconclusive FNA results encompassed categories I, III, and IV of The Bethesda System for Reporting Thyroid Cytopathology(TBSRTC), as well as the ultrasound images indicating malignancy despite FNA results falling under TBSRTC category II. This study assessed the sampling satisfaction rate, diagnostic efficacy, and complications associated with CNB compared to rFNA. Additionally, the impact of repeat puncture time and nodule size on diagnostic efficacy was analyzed., Results: Following repeat punctures, the satisfaction rate of the CNB sampling was found to be significantly higher than that of rFNA (83.9% vs 66.8%). The diagnostic rate in the CNB group was significantly greater compared to that of the rFNA group (70.7% vs 35.8%). In patients with nodule maximum diameters ranging from 5 mm to 20 mm, the diagnostic accuracy was significantly higher in the CNB group compared to that in the rFNA group. In patients with intervals less than 90 days, between 90 days and one year, the diagnostic rate in the CNB group was found to be higher compared to that in the rFNA group. In CNB, not immediately adjacent to the capsule was a risk factor for nodular puncture bleeding (37.0% vs 22.7%.)., Conclusion: CNB demonstrated higher rates of satisfaction and diagnosis compared to the rFNA. The diagnostic effectiveness of CNB was not influenced by the time interval or the size of the thyroid nodule. Therefore, in cases where the initial FNA diagnosis of thyroid nodules is inconclusive, CNB should be considered as a viable option for re-puncture., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Su, Yue, Yang and Ma.)

Background: The role of quantitative contrast-enhanced ultrasound (CEUS) in the evaluation of thyroid nodules with Hashimoto's thyroiditis (HT) has received little attention., Methods: This was a retrospective cohort study. We consecutively enrolled 242 patients (49 males, 193 females, average age 52 years) with a combined total of 248 thyroid nodules coexisting with HT who underwent biopsy/resection-proven pathology from December 2016 to June 2021. All patients underwent preoperative ultrasound (US) and CEUS examinations performed by 2 radiologists independently. Quantitative analysis of CEUS using time-intensity curves (TIC) was measured by an expert radiologist from the thyroid intra-nodule and the surrounding parenchyma and their ratios. Receiver operating characteristic (ROC) analysis was performed to evaluate their diagnostic performance., Results: The patients were divided into the nodular HT (NHT) group (n=42), the papillary thyroid carcinoma (PTC) group (n=154), and the primary thyroid lymphoma (PTL) group (n=52) according to their pathological results. TIC parameters revealed that PTC and PTL showed faster time to peak (TTP) (P=0.044, P=0.049), lower peak intensity (PI) (both P<0.001), and smaller areas under the curve (both P<0.001) than those of NHT. The intra nodule of PTL showed an obviously slower perfusion (ratio =0.90, P<0.001) and lower PI (ratio =0.84, P<0.001) compared with the thyroid parenchyma. TIC improved performance in distinguishing PTL from NHT [area under the curve (AUC): 0.947, 95% confidence interval (CI): 0.903-0.991], but inferior performance in differentiating PTC and NHT (AUC: 0.838, 95% CI: 0.759-0.917)., Conclusions: CEUS quantitative analysis could be valuable in differentiating thyroid malignancies in patients with HT., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-601/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Histone chaperone FACT (facilitates chromatin transcription) is well known to promote chromatin recovery during transcription. However, the mechanism how FACT regulates genome-wide chromatin accessibility and transcription factor binding has not been fully elucidated. Through loss-of-function studies, we show here that FACT component Ssrp1 is required for DNA replication and DNA damage repair and is also essential for progression of cell phase transition and cell proliferation in mouse embryonic fibroblast cells. On the molecular level, absence of the Ssrp1 leads to increased chromatin accessibility, enhanced CTCF binding, and a remarkable change in dynamic range of gene expression. Our study thus unequivocally uncovers a unique mechanism by which FACT complex regulates transcription by coordinating genome-wide chromatin accessibility and CTCF binding., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Myosteatosis indicates pathological fat infiltration in muscles and is regarded as a distinct disease from sarcopenia. This muscular condition exhibits a link to muscle fiber disarrangement coinciding with disrupted muscle contractility and weakened mechanical action, mirrored as decreased muscle quality. However, the relationship between handgrip strength (HGS) and computed tomography-defined myosteatosis among cirrhosis is unclear. We aimed to investigate the association between HGS and myosteatosis and determine gender-specific cutoffs regarding HGS to identify myosteatotic subjects., Methods: We prospectively recruited 221 cirrhotic patients. The presence of myosteatosis was determined according to intramuscular adipose tissue content. The relationship between HGS and myosteatosis was evaluated according to Spearman correlation coefficient, area under the ROC curve, and multivariate logistic regression analysis. Moreover, a model based on the classification and regression tree method was generated., Results: Our results showed that HGS exhibits modestly negative correlation with intramuscular adipose tissue content in the entire cohort (rs = -0.269, P < .001) and across diverse subgroups precluding extremely deteriorating conditions. After controlling for multiple clinical features and biochemical parameters, HGS (odds ratio = 0.921, P = .010) was independently associated with myosteatosis in addition to age and body mass index. On applying the Japan Society of Hepatology-recommended cutoffs, an area under the ROC curve of HGS was 0.627 with a sensitivity of 77.4% and a specificity of 47.9%. The decision tree including body mass index and low HGS correctly classified ~85% of the cases in development and validation sets., Conclusions: HGS was in close relation to myosteatosis among inpatients with cirrhosis., (© The Author(s) 2023. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Agricultural chemicals are commonly used to control pests and weeds, but cause pesticide waste problems. Oil-based emulsions are often used as pesticide formulations to improve pesticide utilization. In this study, the spray visualization experiment of the water and oil-based emulsion butachlor is carried out using an ST flat fan nozzle at 0.1-0.5 MPa pressure. The dimensionless method is used to analyze the difference in liquid sheet fragmentation morphology and disintegration process and the influence of different fragmentation methods on droplet size. It is found that the hydrophobic components in pesticide have a significant effect on the morphology and process of atomization fragmentation. When spray liquid is water, the liquid sheet breaks up into liquid ligaments due to the Rayleigh instability, then the ligaments break up into droplets. The side view of a liquid sheet is a large-amplitude wave disturbance. When the spray liquid is the emulsion butachlor, holes are generated on the liquid sheet, then the holes break up into droplets. The fragmentation method of emulsion spray is the perforation mechanism. Compared with water spray, the presence of the pesticide butachlor increases the droplet size and spray angle and improves the uniformity of droplet size distribution but reduces the breakup length. The spray angle shows a power law dependence of the Weber number with a power of 0.17 for all conditions tested here. At 0.3 MPa, DV50 increases 25%, and span decreases from 1.187 to 1.172. This study could provide reference for the addition of agricultural additives, the improvement of spray operation efficiency, and the establishment of spray fragmentation mechanism., Competing Interests: Author TZ is employed by the company Chinese Academy of Agriculture Mechanization Sciences Group Co., Ltd., Beijing, China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Zhong, Jia, Ou, Dong, Zhang, Ding, Jiang and Wang.)

The purpose of this research is to reveal the internal relationship among community green space, space perception, and activity behavior response to supplement the lack of research results on the binary relationship between green space and behavior. Nine residential community green spaces and 398 residents were selected as the research objects. Thematic clustering and factor identification were used to determine the spatial dimensions of community green space that residents were concerned about. The analysis of the green exposure index, spatial perception evaluation, and activity behavior survey were combined to determine the influence of the green exposure index on spatial perception and activity behavior and its internal correlation path. According to research data, the community green view index (GVI) and normalized difference vegetation index (NDVI) negatively affected the perception factor, while the perception factor positively affected the activity frequency. The SEM model shows that the green exposure index stimulated activity behavior through the intermediate effect of the internal perception path of perceived landscape quality, perceived workability, and perceived accessibility. Spatial perception as the basis of the instantaneous emotional reaction process may affect people's choices for activities but be unable to extend the duration of the activities. The internal association among community green space, spatial perception, and physical activity behavior develops on the basis of spatial patterns at certain scales. This study provides a theoretical basis for understanding the spatial experience and residents' behavioral needs, evaluating the quality of urban green space scientifically, and promoting the optimization of community green space structure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zheng, Zhao, Duan, Yang, Wang and Su.)

In the case of specific immunotherapy regimens and access to pre-treatment CT scans, developing reliable, interpretable intelligent image biomarkers to predict efficacy is essential for physician decision-making and patient treatment selection. However, varying levels of prognosis show a similar appearance on CT scans. It becomes challenging to stratify patients by a single pre-treatment CT scan when presenting subtle differences in images for experienced experts and existing prognostic classification methods. In addition, the pattern of peri-tumoural radiological structures also determines the patient's response to ICIs. Therefore, it is essential to develop a method that focuses on the clinical priori features of the tumour edges but also makes full use of the rich information within the 3D tumour. This paper proposes a priori-guided multilevel graph transformer fusion network (PMSG-Net). Specifically, a graph convolutional network is first used to obtain a feature representation of the tumour edge, and complementary information from that detailed representation is used to enhance the global representation. In the tumour global representation branch (MSGNet), we designed the cascaded scale-enhanced swin transformer to obtain attributes of graph nodes, and efficiently learn and model spatial dependencies and semantic connections at different scales through multi-hop context-aware attention (MCA), yielding a richer global semantic representation. To our knowledge, this is the first attempt to use graph neural networks to predict the efficacy of immunotherapy, and the experimental results show that this method outperforms the current mainstream methods., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

As a critical indicator of how easily the human immune system recognizes tumour cells, tumour mutational burden (TMB) is widely used to identify the potential effectiveness of immune checkpoint inhibitor therapy. However, the difficulties associated with the whole exome sequencing (WES) process, such as high tissue sampling requirements, high costs, and long turnaround times, have hindered the widespread clinical use of WES. Furthermore, the mutation landscape varies across cancer types, and the distribution of TMBs varies across cancer subtypes. Therefore, there is an urgent clinical need to develop a small cancer-specific panel to estimate TMB accurately, predict immunotherapy response cost-effectively and assist physicians in precise decision-making. This paper uses a graph neural network framework (Graph-ETMB) to address the cancer specificity problem in TMB. The correlation and tractability between mutated genes are described through message-passing and aggregation algorithms between graph networks. Then the graph neural network is trained in the lung adenocarcinoma data through a semi-supervised approach, resulting in a mutation panel containing 20 genes with a length of only 0.16 Mb. The number of genes to be detected is smaller than most commercial panels currently in clinical use. In addition, the efficacy of the designed panel in predicting immunotherapy response was further determined in an independent validation dataset, exploring the association between TMB and immunotherapy efficacy., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The associations of circulating trace elements with sleep health have attracted increasing attention given their potential link. However, there is scant data on the relationship between serum trace elements and abnormal sleep duration patterns in cirrhosis. We aimed to investigate these associations with the purpose of identifying modifiable risk factors. The blood samples were collected from inpatients with cirrhosis, and serum levels of several trace elements were assessed by inductively coupled plasma mass spectrometry. Self-reported sleep duration was categorized to short- (< 7 h/night), optimal (7-8 h/night), and long-sleep duration (> 8 h/night). The dose-response trends and associations of trace elements levels with sleep duration were determined by restricted cubic splines (RCS) and logistic regression, respectively. Cirrhotic patients with optimal sleep duration experienced the highest levels of serum Zinc (Zn) and the lowest values of copper to zinc ratio (CZr). RCS model corroborated non-linear associations of serum Zn and CZr against sleep duration. Multiple regression analysis showed that both CZr (short vs optimal sleep duration: OR 4.785, P < 0.001; long vs optimal sleep duration: OR 4.150, P = 0.019) and serum Zn levels (short vs optimal sleep duration: OR 0.985, P = 0.040; long vs optimal sleep duration: OR 0.956, P = 0.008) serve as independent risk factors for sleep duration abnormalities. In conclusion, our findings unraveled a close relationship of serum Zn and CZr with sleep duration in cirrhosis. Further trace element-based therapy such as Zn supplementation may be novel approach to reverse this sleep problem., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Gastric cancer (GC) is a fatal illness, and its mortality rate is very high all over the world. At present, it is a serious health problem for any country. It is a multifactorial disease due to the rising drug resistance and the increasing global cancer burden, the treatment of GC still faces many obstacles and problems. In recent years, research on GC is being carried out continuously, and we hope to address the new targets of GC treatment through this review. At the same time, we also hope to discover new ways to fight GC and create more gospel for clinical patients. First, we discuss the descriptive tumor microenvironment (TME), N6-methyladenosine (m6A), pyroptosis, autophagy, ferroptosis, and cuproptosis. Finally, we expounded on the new or potential targets of GC treatment., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled “Novel Targets for the Treatment of Gastric Cancer”., (Copyright © 2023. Published by Elsevier Masson SAS.)

Background and Aims: Emerging evidence has demonstrated that abnormal body composition may potentiate the development of frailty, whereas little work focuses on the role of divergent adipose tissue. Therefore, we aimed to determine the potential contribution of adipose tissue distribution to multidimensional frailty in decompensated cirrhosis., Methods: We conducted a retrospective cohort study. Divergent adipose tissues were assessed by computed tomography-derived subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI) and total adipose tissue index (TATI), respectively. Frailty was identified by our validated self-reported Frailty Index. Multiple binary logistic models incorporating different covariates were established to assess the relationship between adipose tissue distribution and frailty., Results: The study cohort comprised 245 cirrhotic patients with 45.3% being male. The median Frailty Index, body mass index (BMI) and model for end-stage liver disease (MELD) score were 0.11, 24.3 kg/m 2 and 8.9 points, respectively. In both men and women, patients who were frail exhibited lower levels of SATI in comparison with nonfrail patients. SATI inversely correlated with Frailty Index in the entire cohort (r s =-0.1361, p =0.0332). Furthermore, SATI or TATI was independently associated with frail phenotype in several multiple logistic regression models adjusting for age, BMI, presence of ascites, sodium, Child-Pugh class or MELD score in isolation., Conclusions: In the context of decompensated cirrhosis, low SATI and concomitant TATI were associated with higher risk of being frail. These findings highlight the importance to further apply tissue-specific tools of body composition in place of crude metric like BMI., Competing Interests: CS has been an editorial board member of Journal of Clinical and Translational Hepatology since 2020. The other authors have no conflict of interests related to this publication., (© 2023 Authors.)

Objectives: Malnutrition is prevalent and negatively affects patients with cirrhosis, but a generally accepted consensus pertaining to its diagnosis is lacking. Recently, a framework called the Global Leadership Initiative on Malnutrition (GLIM) has been proposed to diagnose malnutrition, but there is scant evidence regarding its validity. We aimed to investigate associations of malnutrition according to the GLIM criteria, as well as its individual indicator with in-hospital adverse outcomes., Methods: This was a prospective, observational study of consecutively hospitalized patients with cirrhosis. The malnutrition diagnosis was built on a stepwise GLIM process with initial screening, followed by fulfillment of at least one phenotypic and one etiologic criterion. Patients were followed up for a combined endpoint of in-hospital mortality and prolonged length of stay (LOS). Covariates compromise malnutrition according to the GLIM criteria and its indicators in separation. Logistic regression analyses were implemented to determine predictive validity., Results: A total of 387 cirrhotic patients were assessed. Malnutrition was diagnosed in 28.7% of patients according to the GLIM criteria, and increased the risk of in-hospital mortality and prolonged LOS by 2.166 and 1.767 times, respectively, adjusting for age, sex, biochemical parameters, and clinical scores of disease severity. When analyzing separate criteria, all constituents were independently associated with in-hospital adverse outcomes, adjusting for model for end-stage liver disease sodium score., Conclusions: Malnutrition according to the GLIM criteria was considerably prevalent among hospitalized patients with cirrhosis, and associated with approximately two times greater probability of in-hospital mortality and prolonged LOS. These diagnostic criteria may be implemented and disseminated during daily practice considering their predictive validity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study investigated the effects of exogenous salicylic acid (SA) treatment (0, control; 3 mmol L -1 ) on the antioxidant and hormone levels of winter jujube during shelf life (20 d) at 4 °C. The results showed that 3 mmol L -1 SA treatment preferably maintained firmness, color, titratable acidity, and total soluble solids, and effectively reduced the respiratory intensity and TSS/TA value (13.08%) of the fruit. Compared with the control group, the SA group had a higher content of sucrose (14.03%) and malic acid (29.13%). Meanwhile, SA reduced the accumulation of H 2 O 2 (27.73%) and O 2 - (45.44%) by enhancing the activity of antioxidant enzymes (superoxide dismutase, peroxidase, catalase, ascorbate peroxidase) and the content of antioxidant substances (ascorbic acid, total phenols, total flavonoids, and glutathione) in the fruit. In addition, 3 mmol L -1 SA treatment led to higher levels of endogenous abscisic acid (18.49%) and SA (20.47%) in fruit, and lower concentration of jasmonic acid (42.68%), but had a weak effect on indole acetic acid levels., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Self-compassion is beneficial for individuals' emotional health, but debates regarding its conceptualization are increasing. The present study aimed to explore the neural basis of self-compassion and its compassionate and uncompassionate dimensions and the indirect path from neural basis to emotional health. Structural MRI and Resting-state fMRI data were used to measure the gray matter volume (GMV) and the amplitude of low-frequency fluctuation (ALFF) in 88 healthy college students. We found that individuals with higher self-compassion had decreased GMV in the prefrontal cortex, cerebellum as well as lower ALFF in the occipital lobe. The compassionate and uncompassionate dimensions of self-compassion shared some similarities (e.g., common correlation with GMV in the medial prefrontal cortex, ALFF in the occipital lobe) but also had some differences (e.g., only uncompassionate dimensions correlated with GMV in the lateral prefrontal cortex, ALFF in medial temporal lobe/striatum). The indirect path analyses revealed that corresponding brain characteristics could have associations with emotional health through self-compassion, as well as its uncompassionate dimension, but not compassionate dimension. This exploratory whole-brain study showed some preliminary findings that compassionate and uncompassionate dimensions of self-compassion were related to distinct brain regions, which are both important to the current conceptualization of self-compassion and intervention study., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We have clarified that malnutrition risk evaluated by the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) is prevalent in patients with cirrhosis. Mineral elements (zinc, iron, magnesium, copper, manganese, and calcium) are micronutrients essential for versatile physiological processes and cellular bioactivities. However, the association between these trace elements and integral nutritional status is unclear in decompensated cirrhotics. We collected blood samples from hospitalized patients with cirrhosis, and serum trace element concentrations were examined by inductively coupled plasma mass spectrometry. Association of trace element levels with high malnutrition risk was determined by multivariate logistic regression model. Sera from 141 patients with decompensated cirrhosis were analyzed for a total of six trace element concentrations. No significant differences were observed between high and low/moderate RFH-NPT malnutrition risk groups with the exception of zinc. The serum zinc concentrations were significantly decreased in patients at high malnutrition risk when compared to low/moderate subjects (57.9 vs 68.1 μg/dL, P = 0.006). In terms of receiver operating characteristics curve, zinc < 64 μg/dL represented best discriminative capability with an area of 0.635 (95% CI: 0.542, 0.728). Patients in the group with zinc < 64 μg/dL had elevated RFH-NPT and MELD score, higher proportion of Child-Pugh class C and ascites, higher CRP, lower albumin and sodium than in the group with zinc ≥ 64 μg/dL. Zinc < 64 μg/dL was an independent risk factor for high malnutrition risk. Low levels of serum zinc referring to less than 64 μg/dL were associated with poor integral nutritional status in cirrhosis., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Accurate prediction of the tumor's future imaging features can provide its complete growth evolution and more detailed clinical parameters. The existing longitudinal models tend to lose detailed growth information and make it difficult to model the complete tumor development process. In this paper, we propose the Static-Dynamic coordinated Transformer for Tumor Longitudinal Growth Prediction (SDC-Transformer). To extract the static high-level features of tumors in each period, and to further explore the dynamic growth associations and expansion trend of tumors between different periods. Aiming at the insensitivity to local pixel information of the Transformer, we propose the Local Adaptive Transformer Module to facilitate a strongly coupled status of feature images, which ensures the characterization of tumor complex growth trends. Faced with the dynamic changes brought about by tumor growth, we introduce the Dynamic Growth Estimation Module to predict the future growth trend of the tumor. As a core part of SDC-Transformer, we design the Enhanced Deformable Convolution to enrich the sampling space of tumor growth pixels. And a novel Cascade Self-Attention is performed under multi-growth imaging to obtain dynamic growth relationships between periods and use dual cascade operations to predict the tumor's future expansion trajectories and growth contours. Our SDC-Transformer is rigorously trained and tested on longitudinal tumor data composed of the National Lung Screening Trial (NLST) and collaborative Shanxi Provincial People's Hospital. The RMSE, Dice, Recall, and Specificity of the longitudinal prediction results reach 11.32, 89.31%, 90.57%, and 89.64%, respectively. This result shows that our proposed SDC-Transformer model can achieve accurate longitudinal prediction of tumors, which will help physicians to establish specific treatment plans and accurately diagnose lung cancer. The code will be released soon., (Copyright © 2022. Published by Elsevier Ltd.)

In this paper, a phase-field model of Si-doped hafnium oxide-based ferroelectric thin films is established. And then, the synergistic effect of Si concentration and distribution on ferroelectric properties optimization of Si:HfO 2 ferroelectric thin films is studied with the proposed model. It is found that no matter how Si dopant is distributed in the film, the volume fraction of the ferroelectric phase in the film increases first and then decreases with the increase of Si concentration. However, compared with the uniform distribution, the layered distribution is more likely to great improve ferrelectric properties. When Si dopant is uniformly distributed in the film, the highest remanent polarization value that the film can obtain via Si concentration modulation is 38.7 μ C cm -2 , and the corresponding Si concentration is 3.8 cat%, which is consistent with the experimental results. When Si dopant is layered in the film, and the concentration difference between the Si-rich and Si-poor layers is 7.6%, in the Si concentration range of 3.6 cat%-3.8 cat%, the residual polarization of the film reaches 46.4-46.8 μ C cm -2 , which is 20% higher than that when Si dopant are evenly distributed in the film. The above results show that selecting the Si layered distribution mode and controlling the concentration difference between Si-rich and Si-poor layers in an appropriate range can greatly improve the films' ferroelectric properties and broaden the Si concentration optimization range of the ferroelectric properties of the films. The result provides further theoretical guidance on using Si doping to adjust the ferroelectric properties of hafnium oxide-based films., (© 2022 IOP Publishing Ltd.)

This study aimed to explore the mediation process from maternal mindful parenting to adolescent internalizing and externalizing problems through mother-child communication and adolescent self-disclosure. A total of 496 mother-adolescent dyads participated in the current study. Mother-reported mindful parenting and mother-child communication and adolescent-reported self-disclosure and behavior problems were collected. Path analysis results showed that mothers' mindful parenting was indirectly associated with adolescent internalizing and externalizing behaviors through mother-child communication and adolescent self-disclosure. In addition, the specific components of mindful parenting were examined in detail. The component of interacting with full attention showed unique patterns, while components of compassion and acceptance and emotion awareness of children showed similar pattern with the total score. These findings contribute to the knowledge of the mechanism underlying how mindful parenting benefit adolescent internalizing and externalizing behaviors, and have implications for clinical interventions., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Medical imaging data of lung cancer in different stages contain a large amount of time information related to its evolution (emergence, development, or extinction). We try to explore the evolution process of lung images in time dimension to improve the prediction of lung cancer survival by using longitudinal CT images and clinical data jointly., Methods: In this paper, we propose an innovative multi-branch spatiotemporal residual network (MS-ResNet) for disease-specific survival (DSS) prediction by integrating the longitudinal computed tomography (CT) images at different times and clinical data. Specifically, we first extract the deep features from the multi-period CT images by an improved residual network. Then, the feature selection algorithm is used to select the most relevant feature subset from the clinical data. Finally, we integrate the deep features and feature subsets to take full advantage of the complementarity between the two types of data to generate the final prediction results., Results: The experimental results demonstrate that our MS-ResNet model is superior to other methods, achieving a promising 86.78% accuracy in the classification of short-survivor, med-survivor, and long-survivor., Conclusion: In computer-aided prognostic analysis of cancer, the time dimension features of the course of disease and the integration of patient clinical data and CT data can effectively improve the prediction accuracy., (© 2022. CARS.)

Background: Dynamic changes of histone posttranslational modifications are important contexts of epigenetic reprograming after fertilization in pre-implantation embryos. Recently, lactylation has been reported as a novel epigenetic modification that regulates various cellular processes, but its role during early embryogenesis has not been elucidated., Results: We examined nuclear accumulation of H3K23la, H3K18la and pan histone lactylation in mouse oocytes and pre-implantation embryos by immunofluorescence with specific antibodies. All of the three modifications were abundant in GV stage oocytes, and both H3K23la and pan histone lactylation could be detected on the condensed chromosomes of the MII oocytes, while H3K18la were not detected. After fertilization, the nuclear staining of H3K23la, H3K18la and pan histone lactylation was faint in zygotes but homogeneously stained both of the parental pronuclei. The signal remained weak in the early cleavage stage embryos and increased remarkably in the blastocyst stage embryos. Comparison of the embryos cultured in four different conditions with varying concentrations of oxygen found that H3K23la, H3K18la and pan histone lactylation showed similar and comparable staining pattern in embryos cultured in atmospheric oxygen concentration (20% O 2 ), gradient oxygen concentration (5% O 2 to 2% O 2 ) and embryos obtained from in vivo, but the modifications were greatly reduced in embryos cultured in hypoxic condition (2% O 2 ). In contrast, nuclear accumulation of H3K18ac or H3K23ac was not significantly affected under hypoxic condition. Moreover, the developmental rate of in vitro cultured embryo was significantly reduced by low oxygen concentration and small molecule inhibition of LDHA activity led to decreased lactate production, as well as reduced histone lactylation and compromised developmental rate., Conclusions: We provided for the first time the dynamic landscape of H3K23la, H3K18la and pan histone lactylation in oocytes and pre-implantation embryos in mice. Our data suggested that histone lactylation is subjected to oxygen concentration in the culture environment and hypoxic in vitro culture reduces histone lactylation, which in turn compromises developmental potential of pre-implantation embryos in mice., (© 2021. The Author(s).)

Wake-up effect and fatigue in HfO 2 -based ferroelectric films are closely related to the phase transition dynamics of the film subjected to ultrafast electric pulses. Here, we establish a multiphase coexistence phase field dynamics model for HfO 2 -based ferroelectric films in the ultrafast time scale and study the effects of the amplitude, width and frequency of the electric pulse on the phase transition dynamics. Based on the simulation results, we obtain the analytical equation of the volume fraction of switched c -domains under low fields as a function of pulse duration. And we found that monoclinic phase can transform into ferroelectric c -domains under high amplitude electric field ( E ⩾ 2.8 MV cm -1 ). The electric pulse duration affects the film's retention properties. When the duration of the electric pulse is less than 1.2 ns or longer than 1.8 ns, the ferroelectric c -domains will respectively invert into other phases or increase cumulatively after removing the electric field. The frequency of cyclic pulse is related to the degree of wake up effect. The lower the pulse frequency is, the more obvious the 'wake up' effect is., (© 2021 IOP Publishing Ltd.)

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder in women, which is characterized by androgen excess, ovulation dysfunction, and polycystic ovary. Although the etiology of PCOS is largely unknown, many studies suggest that aberrant DNA methylation is an important contributing factor for its pathological changes. In this study, we investigated DNA methylation characteristics and their impact on gene expression in granulosa cells obtained from PCOS patients. Transcriptome analysis found that differentially expressed genes were mainly enriched in pathways of insulin resistance, fat cell differentiation, and steroid metabolism in PCOS. Overall DNA methylation level in granulosa cells was reduced in PCOS, and the first introns were found to be the major genomic regions that were hypomethylated in PCOS. Integrated analysis of transcriptome, DNA methylation, and miRNAs in ovarian granulosa cells revealed a DNA methylation and miRNA coregulated network and identified key candidate genes for pathogenesis of PCOS, including BMP4, ETS1, and IRS1. Our study shed more light on epigenetic mechanism of PCOS and provided valuable reference for its diagnosis and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cao, Yang, Wang, Li and Nashun.)