Real-time predictive model of extrauterine growth retardation in preterm infants with gestational age less than 32 weeks.

The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0-95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.

Mixotrophic denitrification of waste activated sludge fermentation liquid as an alternative carbon source for nitrogen removal: Reducing N2O emissions and costs.

Heterotrophic-sulfur autotrophic denitrification (HAD) has been proposed to be a prospective nitrogen removal process. In this work, the potential of fermentation liquid (FL) from waste-activated sludge (WAS) as the electron donor for denitrification in the HAD system was explored and compared with other conventional carbon sources. Results showed that when FL was used as a carbon source, over 99% of NO3--N was removed and its removal rate exceeded 14.00 mg N/g MLSS/h, which was significantly higher than that of methanol and propionic acid. The produced sulfate was below the limit value and the emission of N2O was low (1.38% of the NO3--N). Microbial community analysis showed that autotrophic denitrifiers were predominated in the HAD system, in which Thiobacillus (16.4%) was the dominant genus. The economic analysis showed the cost of the FL was 0.062 €/m3, which was 30% lower than that in the group dosed with methanol. Our results demonstrated the FL was a promising carbon source for the HAD system, which could reduce carbon emission and cost, and offer a creative approach for waste-activated sludge resource reuse.

Aptamer-based assembly systems for SARS-CoV-2 detection and therapeutics.

Nucleic acid aptamers are oligonucleotide chains with molecular recognition properties. Compared with antibodies, aptamers show advantages given that they are readily produced via chemical synthesis and elicit minimal immunogenicity in biomedicine applications. Notably, aptamer-encoded nucleic acid assemblies further improve the binding affinity of aptamers with the targets due to their multivalent synergistic interactions. Specially, aptamers can be engineered with special topological arrangements in nucleic acid assemblies, which demonstrate spatial and valence matching towards antigens on viruses, thus showing potential in the detection and therapeutic applications of viruses. This review presents the recent progress on the aptamers explored for SARS-CoV-2 detection and infection treatment, wherein applications of aptamer-based assembly systems are introduced in detail. Screening methods and chemical modification strategies for aptamers are comprehensively summarized, and the types of aptamers employed against different target domains of SARS-CoV-2 are illustrated. The evolution of aptamer-based assembly systems for the detection and neutralization of SARS-CoV-2, as well as the construction principle and characteristics of aptamer-based DNA assemblies are demonstrated. The typically representative works are presented to demonstrate how to assemble aptamers rationally and elaborately for specific applications in SARS-CoV-2 diagnosis and neutralization. Finally, we provide deep insights into the current challenges and future perspectives towards aptamer-based nucleic acid assemblies for virus detection and neutralization in nanomedicine.

Thermostability-assisted limited proteolysis-coupled mass spectrometry for capturing drug target proteins and sites.

BACKGROUND: Identifying drug-binding targets and their corresponding sites is crucial for drug discovery and mechanism studies. Limited proteolysis-coupled mass spectrometry (LiP-MS) is a sophisticated method used for the detection of compound and protein interactions. However, in some cases, LiP-MS cannot identify the target proteins due to the small structure changes or the lack of enrichment of low-abundant protein. To overcome this drawback, we developed a thermostability-assisted limited proteolysis-coupled mass spectrometry (TALiP-MS) approach for efficient drug target discovery. RESULTS: We proved that the novel strategy, TALiP-MS, could efficiently identify target proteins of various ligands, including cyclosporin A (a calcineurin inhibitor), geldanamycin (an HSP90 inhibitor), and staurosporine (a kinase inhibitor), with accurately recognizing drug-binding domains. The TALiP protocol increased the number of target peptides detected in LiP-MS experiments by 2- to 8-fold. Meanwhile, the TALiP-MS approach can not only identify both ligand-binding stability and destabilization proteins but also shows high complementarity with the thermal proteome profiling (TPP) and machine learning-based limited proteolysis (LiP-Quant) methods. The developed TALiP-MS approach was applied to identify the target proteins of celastrol (CEL), a natural product known for its strong antioxidant and anti-cancer angiogenesis effect. Among them, four proteins, MTHFD1, UBA1, ACLY, and SND1 were further validated for their strong affinity to CEL by using cellular thermal shift assay. Additionally, the destabilized proteins induced by CEL such as TAGLN2 and CFL1 were also validated. SIGNIFICANCE: Collectively, these findings underscore the efficacy of the TALiP-MS method for identifying drug targets, elucidating binding sites, and even detecting drug-induced conformational changes in target proteins in complex proteomes.

Scoping review: Exploring the relationship between chrononutrition and glycemic responses in the adult population.

Chrononutrition, an emerging body of evidence on the relationship between biological rhythms and metabolism, has been established to be associated with glycemic responses. However, the available evidence is inconsistent, due to protocol variations. Therefore, this review aims to summarize the findings on chrononutrition characteristics and their association with glycemic responses among adults. Systematic searches were conducted across six databases (PubMed, EBSCO Host, ProQuest Central, MEDLINE & Ovid, Scopus and Web of Science) to identify all relevant studies published from January 2012. Two reviewers independently screened the abstracts and full-text articles based on the inclusion and exclusion criteria. Details about population characteristics, study methods and key findings were extracted following the PRISMA-ScR guideline. The quality of selected studies was evaluated using the mixed methods appraisal tool. The searchers identified 49 studies eligible for analysis. The results showed that meal timing, particularly night-time eating and snacking were associated with glycemic responses. Regarding meal regularity, skipping breakfast may affect glycemic responses, but no clear conclusion was drawn about its effect on insulin. The association between meal frequency and glycemic responses was inconclusive. Night fasting duration and restricted eating window are potentially associated with glycemic responses. The current review extensively investigates the association between chrononutrition factors and glycemic responses in adults. However, more prospective cohort and interventional studies are needed to better understand this causal-effect relationship.

Development and reproduction of Scirtothrips dorsalis (Thysanoptera: Thripidae) on six host plant species.

Host plants can strongly influence the population performance of insects. Here, we investigated the development, survival, and oviposition of Scirtothrips dorsalis Hood on 6 host plants-Camellia sinensis ( L.) Kuntze (Ericales: Theaceae), Rosa chinensis Jacq. (Rosales: Rosaceae), Capsicum annuum L. (Solanales: Solanaceae), Eustoma grandiflorum (Hook.) G.Don (Gentianales: Gentianaceae), Glycine max (L.) Merr. (Fabales: Fabaceae), and Cucumis sativus L. (Cucurbitales: Cucurbitaceae), and constructed life tables for S. dorsalis on each plant. Significant differences in S. dorsalis development on the host species were observed. The mean developmental period from egg to adult was 11.45 ±â€…0.12 days, 11.24 ±â€…0.13 days, 12.08 ±â€…0.15 days, 12.28 ±â€…0.12 days, 12.67 ±â€…0.10 days, and 13.03 ±â€…0.11 days on C. sinensis, R. chinensis, C. annuum, E. grandiflorum, G. max, and C. sativus, respectively. Significant differences in survival of S. dorsalis were observed, namely, C. sinensis ≈ R. chinensis > E. grandiflorum ≈ C. annuum > G. max > C. sativus. The highest and lowest fecundities of S. dorsalis were recorded on R. chinensis (60.44 ±â€…1.53) and C. sativus (28.64 ±â€…1.02), respectively. Both of the net reproductive rate (R0) and intrinsic rate of increase (rm) of S. dorsalis were the highest on R. chinensis, with the values of 27.63 ±â€…0.58 and 0.142 ±â€…0.002, respectively; while the lowest on C. sativus, with the values of 8.81 ±â€…0.12 and 0.092 ±â€…0.003, respectively. Thus, R. chinensis was found to be the most suitable host, but C. sativus was the least suitable, for population development of S. dorsalis. Our results provide important information for the key control of S. dorsalis among different host plants.

Altered nucleocytoplasmic export of adenosine-rich circRNAs by PABPC1 contributes to neuronal function.

Circular RNAs (circRNAs) are upregulated during neurogenesis. Where and how circRNAs are localized and what roles they play during this process have remained elusive. Comparing the nuclear and cytoplasmic circRNAs between H9 cells and H9-derived forebrain (FB) neurons, we identify that a subset of adenosine (A)-rich circRNAs are restricted in H9 nuclei but exported to cytosols upon differentiation. Such a subcellular relocation of circRNAs is modulated by the poly(A)-binding protein PABPC1. In the H9 nucleus, newly produced (A)-rich circRNAs are bound by PABPC1 and trapped by the nuclear basket protein TPR to prevent their export. Modulating (A)-rich motifs in circRNAs alters their subcellular localization, and introducing (A)-rich circRNAs in H9 cytosols results in mRNA translation suppression. Moreover, decreased nuclear PABPC1 upon neuronal differentiation enables the export of (A)-rich circRNAs, including circRTN4(2,3), which is required for neurite outgrowth. These findings uncover subcellular localization features of circRNAs, linking their processing and function during neurogenesis.

Peer Facilitator Training for Diabetes Prevention in a Nigerian Drug Treatment Center.

INTRODUCTION AND BACKGROUND: Individuals with substance use disorders (SUDs) are at an increased risk of developing comorbid medical conditions, including Type 2 diabetes. Although the diabetes prevention program (DPP) is efficacious and cost-effective, there is no published evidence to support its implementation in Nigeria or within SUD treatment settings. In this first known DPP within an SUD treatment program, we implemented a multiphased, nurse-led DPP at a small outpatient drug treatment center in Nigeria. The aim of this article was to describe only the processes utilized for the initial peer facilitator (PF) training (Phase 1). METHODS: In Phase 1, a diabetes prevention master trainer delivered a virtual DPP training to the facility's lead nurse, who return-demonstrated the DPP workshop skills and competencies over four 4-hour sessions. The lead nurse then independently delivered four 8-hour training sessions to a small number of client volunteers (n = 4) who subsequently delivered the DPP lifestyle interventions to their peers in the outpatient treatment program. RESULTS: The client volunteers attended all PF workshop sessions and were observed to be proficient in all aspects of implementation. They indicated that the training objectives were easily achieved and expressed enthusiasm for delivering DPP content to their peers. The need to better contextualize the DPP curriculum specific to Nigerian food preferences was identified. CONCLUSION: The Phase 1 training process appears to be an appropriate and effective approach for preparing PFs to deliver health programs, like the DPP, in environments with limited resources for populations facing numerous challenges.

Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction.

BACKGROUND: Leukemia stem cells (LSCs) are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia (AML), as they are protected by the bone marrow microenvironment (BMM) against conventional therapies. Gossypol acetic acid (GAA), which is extracted from the seeds of cotton plants, exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2. AIM: To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism. METHODS: In this study, LSCs were magnetically sorted from AML cell lines and the CD34+CD38- population was obtained. The expression of leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) and forkhead box M1 (FOXM1) was evaluated in LSCs, and the effects of GAA on malignancies and mitochondrial function were measured. RESULTS: LRPPRC was found to be upregulated, and GAA inhibited cell proliferation by degrading LRPPRC. GAA induced LRPPRC degradation and inhibited the activation of interleukin 6 (IL-6)/janus kinase (JAK) 1/signal transducer and activator of transcription (STAT) 3 signaling, enhancing chemosensitivity in LSCs against conventional chemotherapies, including L-Asparaginase, Dexamethasone, and cytarabine. GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC. Furthermore, GAA induced reactive oxygen species accumulation, disturbed mitochondrial homeostasis, and caused mitochondrial dysfunction. By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC, GAA resulted in the elimination of LSCs. Meanwhile, GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage. CONCLUSION: Taken together, the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

High-integrity Pueraria montana var. lobata genome and population analysis revealed the genetic diversity of Pueraria genus.

Pueraria montana var. lobata (P. lobata) is a traditional medicinal plant belonging to the Pueraria genus of Fabaceae family. Pueraria montana var. thomsonii (P. thomsonii) and Pueraria montana var. montana (P. montana) are its related species. However, evolutionary history of the Pueraria genus is still largely unknown. Here, a high-integrity, chromosome-level genome of P. lobata and an improved genome of P. thomsonii were reported. It found evidence for an ancient whole-genome triplication and a recent whole-genome duplication shared with Fabaceae in three Pueraria species. Population genomics of 121 Pueraria accessions demonstrated that P. lobata populations had substantially higher genetic diversity, and P. thomsonii was probably derived from P. lobata by domestication as a subspecies. Selection sweep analysis identified candidate genes in P. thomsonii populations associated with the synthesis of auxin and gibberellin, which potentially play a role in the expansion and starch accumulation of tubers in P. thomsonii. Overall, the findings provide new insights into the evolutionary and domestication history of the Pueraria genome and offer a valuable genomic resource for the genetic improvement of these species.

Hyperbaric Lidocaine Aggravates Diabetic Neuropathic Pain by Targeting p38 MAPK/ERK and PINK1/Parkin-Mediated Mitophagy Signaling Pathway.

BACKGROUND: Diabetic neuropathic pain (DNP) is a complication of diabetes mellitus (DM). Hyperbaric lidocaine (HL), a local anesthetics drug, has neurotoxicity. The present study aims to study the effect and molecular mechanisms of HL on spinal nerve injury in DNP. METHODS: The DNP rat model was established through a high-fat-glucose diet in combination with Streptozotocin (STZ) administration. SB203580 and PD98059 were utilized to inhibit p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated kinase (ERK). The mechanical paw withdrawal threshold (PWT) and the thermal paw withdrawal latency (PWL) were tested to evaluate rats' mechanical allodynia and thermal hyperalgesia. Hematoxylin-eosin (H&E) and terminal deoxynucleotidyltransferase-mediated dUTP nick-end Labeling (TUNEL) staining were performed to evaluate the pathological changes and neuron apoptosis in spinal cord tissues of L4-5. Western blotting analysis and reverse transcription-polymerase chain reaction (RT-qPCR) assay were used to measure the levels of proteins and mRNAs, respectively. RESULTS: PWT and PWL were decreased in DNP rats with serious spinal nerve injury. HL administration downregulated the PWT and PWL and aggravated spinal nerve injury in DNP rats, but isobaric lidocaine had no effects on these changes. Meanwhile, p38 MAPK/ERK signaling and PTEN-induced kinase 1 (PINK1)-mediated mitophagy were activated in DNP, which was enhanced by HL but not isobaric lidocaine. Blocking p38 MAPK/ERK signaling could effectively attenuate HL-induced spinal nerve injury and inhibit mitophagy. CONCLUSION: In summary, HL can aggravate spinal cord tissue damage in DNP rats by inducing PINK1-mediated mitophagy via activating p38 MAPK/ERK signaling. Our data provide a novel insight that supports the potential role of p38 MAPK/ERK signaling in acting as a therapeutic target for HL-induced neurotoxicity.

Predicting Driving Cessation Among Cognitively Normal Older Drivers: The Role of Alzheimer Disease Biomarkers and Clinical Assessments.

BACKGROUND AND OBJECTIVES: With the aging US population and increasing incidence of Alzheimer disease (AD), understanding factors contributing to driving cessation among older adults is crucial for clinicians. Driving is integral for maintaining independence and functional mobility, but the risk factors for driving cessation, particularly in the context of normal aging and preclinical AD, are not well understood. We studied a well-characterized community cohort to examine factors associated with driving cessation. METHODS: This prospective, longitudinal observation study enrolled participants from the Knight Alzheimer Disease Research Center and The DRIVES Project. Participants were enrolled if they were aged 65 years or older, drove weekly, and were cognitively normal (Clinical Dementia Rating [CDR] = 0) at baseline. Participants underwent annual clinical, neurologic, and neuropsychological assessments, including ß-amyloid PET imaging and CSF (Aß42, total tau [t-Tau], and phosphorylated tau [p-Tau]) collection every 2-3 years. The primary outcome was time from baseline visit to driving cessation, accounting for death as a competing risk. The cumulative incidence function of driving cessation was estimated for each biomarker. The Fine and Gray subdistribution hazard model was used to examine the association between time to driving cessation and biomarkers adjusting for clinical and demographic covariates. RESULTS: Among the 283 participants included in this study, there was a mean follow-up of 5.62 years. Driving cessation (8%) was associated with older age, female sex, progression to symptomatic AD (CDR ≥0.5), and poorer performance on a preclinical Alzheimer cognitive composite (PACC) score. Aß PET imaging did not independently predict driving cessation, whereas CSF biomarkers, specifically t-Tau/Aß42 (hazard ratio [HR] 2.82, 95% CI 1.23-6.44, p = 0.014) and p-Tau/Aß42 (HR 2.91, 95% CI 1.28-6.59, p = 0.012) ratios, were independent predictors in the simple model adjusting for age, education, and sex. However, in the full model, progression to cognitive impairment based on the CDR and PACC score across each model was associated with a higher risk of driving cessation, whereas AD biomarkers were not statistically significant. DISCUSSION: Female sex, CDR progression, and neuropsychological measures of cognitive functioning obtained in the clinic were strongly associated with future driving cessation. The results emphasize the need for early planning and conversations about driving retirement in the context of cognitive decline and the immense value of clinical measures in determining functional outcomes.

Automatic 3D left atrial strain extraction framework on cardiac computed tomography.

BACKGROUND AND OBJECTIVE: Strain analysis provides insights into myocardial function and cardiac condition evaluation. However, the anatomical characteristics of left atrium (LA) inherently limit LA strain analysis when using echocardiography. Cardiac computed tomography (CT) with its superior spatial resolution, has become critical for in-depth evaluation of LA function. Recent studies have explored the feasibility of CT-derived strain; however, they relied on manually selected regions of interest (ROIs) and mainly focused on left ventricle (LV). This study aimed to propose a first-of-its-kind fully automatic deep learning (DL)-based framework for three-dimensional (3D) LA strain extraction on cardiac CT. METHODS: A total of 111 patients undergoing ECG-gated contrast-enhanced CT for evaluating subclinical atrial fibrillation (AF) were enrolled in this study. We developed a 3D strain extraction framework on cardiac CT images, containing a 2.5D GN-U-Net network for LA segmentation, axis-oriented 3D view extraction, and LA strain measure. The segmentation accuracy was evaluated using Dice similarity coefficient (DSC). The model-extracted LA volumes and emptying fraction (EF) were compared with ground-truth measurements using intraclass correlation coefficient (ICC), correlation coefficient (r), and Bland-Altman plot (B-A). The automatically extracted LA strains were evaluated against the LA strains measured from 2D echocardiograms. We utilized this framework to gauge the effect of AF burden on LA strain, employing the atrial high rate episode (AHRE) burden as the measurement parameter. RESULTS: The GN-U-Net LA segmentation network achieved a DSC score of 0.9603 on the test set. The framework-extracted LA estimates demonstrated excellent ICCs of 0.949 (95 % CI: 0.93-0.97) for minimal LA volume, 0.904 (95 % CI: 0.86-0.93) for maximal LA volume, and 0.902 (95 % CI: 0.86-0.93) for EF, compared with expert measurements. The framework-extracted LA strains demonstrated moderate agreement with the LA strains based on 2D echocardiography (ICCs >0.703). Patients with AHRE > 6 min had significantly lower global strain and LAEF, as extracted by the framework than those with AHRE ≤ 6 min. CONCLUSION: The promising results highlighted the feasibility and clinical usefulness of automatically extracting 3D LA strain from CT images using a DL-based framework. This tool could provide a 3D-based alternative to echocardiography for assessing LA function.

Operando Building of a Superior Interface Hybrid Film Enables Chemomechanically Durable Co-Free Ni-Rich Cathodes.

The Co-free Ni-rich layered cathodes become pivotal to reduce cost and increase benefit toward next-generation Li-ion batteries yet raise a major challenge for their extremely fragile cathode-electrolyte interface (CEI) film. Herein, we report the in situ construction of the Si/B-enriched organic-inorganic hybrid CEI films on LiNi0.9Mn0.1O2 (NM91) with the assistance of tris(trimethylsilyl) borate (TMSB) additive. The hybrid film exhibits superior Young's modulus, mechanical strength, and ductility, which greatly dissipate the microstrain of Co-free Ni-rich cathodes under various states of charge with high structural integrity. Furthermore, the surface oxygen anions have been significantly stabilized by bonding with the Si and B ions of TMSB with high safety. These merits enable a durable Co-free Ni-rich layered cathode with 96.9% and 87.7% capacity retentions (versus 72.7% and 70.2% of NM91) at a high rate of 5C and a high-temperature of 55 °C after 100 cycles. In a pouch-type full cell, 88.8% of initial capacity is still maintained after cycling at 1C for 500 times, greatly expediting the development and application of Co-free Ni-rich layered cathodes.

[Control status and follow-up of acute attacks in children with bronchial asthma with normal pulmonary ventilation function]. / è‚ºé€šæ°”åŠŸèƒ½æ­£å¸¸çš„å„¿ç«¥æ”¯æ°”ç®¡å“®å–˜æŽ§åˆ¶æƒ å†µåŠæ€¥æ€§å‘ä½œéšè®¿çš„ç ”ç©¶.

OBJECTIVES: To investigate the control status of bronchial asthma (referred to as "asthma") in school-age children with normal pulmonary ventilation function and the occurrence of acute attacks within 1 year of follow-up. METHODS: A retrospective analysis was conducted on clinical data of 327 children aged 6-14 years with bronchial asthma and normal pulmonary ventilation function from April to September 2021. Based on the measured value of one second rate (FEV1/FVC), the children were divided into the ≥80% group (267 cases) and the <80% group (60 cases). The pulmonary ventilation function, asthma control level, and occurrence of acute attacks within 1 year were compared between the two groups. RESULTS: The baseline pulmonary ventilation function in the <80% group was lower than that in the ≥80% group, and the proportion of small airway dysfunction was higher than that in the ≥80% group (P<0.05). After standardized treatment for 1 year, the small airway function indices in the <80% group improved but remained lower than those in the ≥80% group (P<0.05). The rate of incomplete asthma control at baseline was 34.6% (113/327), and the asthma control level in the <80% group was lower than that in the ≥80% group (P<0.05). After standardized treatment for 1 year, the asthma control level in the <80% group remained lower than that in the ≥80% group, and the proportion of acute asthma attacks was higher than that in the ≥80% group (P<0.05). CONCLUSIONS: Approximately one-third of school-age children with asthma still have incomplete asthma control when their pulmonary ventilation function is normal. Among them, children with measured FEV1/FVC<80% have an increased risk of acute asthma attacks and require close follow-up and strengthened asthma management.

Use of computed tomography to identify muscle quality subgroups, spatial mapping, and preliminary relationships to function in those with diabetic peripheral neuropathy.

BACKGROUND: Decreased muscle volume and increased muscle-associated adipose tissue (MAAT, sum of intra and inter-muscular adipose tissue) of the foot intrinsic muscle compartment are associated with deformity, decreased function, and increased risk of ulceration and amputation in those with diabetic peripheral neuropathy (DPN). RESEARCH QUESTION: What is the muscle quality (normal, abnormal muscle, and adipose volumes) of the DPN foot intrinsic compartment, how does it change over time, and is muscle quality related to gait and foot function? METHODS: Computed tomography was performed on the intrinsic foot muscle compartment of 45 subjects with DPN (mean age: 67.2 ± 6.4 years) at baseline and 3.6 years. Images were processed to obtain volumes of MAAT, highly abnormal, mildly abnormal, and normal muscle. For each category, annual rates of change were calculated. Paired t-tests compared baseline and follow-up. Foot function during gait was assessed using 3D motion analysis and the Foot and Ankle Ability Measure. Correlations between muscle compartment and foot function during gait were analyzed using Pearson's correlations. RESULTS: Total muscle volume decreased, driven by a loss of normal muscle and mildly abnormal muscle (p<0.05). MAAT and the adipose-muscle ratio increased. At baseline, 51.5% of the compartment was abnormal muscle or MAAT, increasing to 55.0% at follow-up. Decreased total muscle volume correlated with greater midfoot collapse during gait (r = -0.40, p = 0.02). Greater volumes of highly abnormal muscle correlated with a lower FAAM score (r = -0.33, p = 0.03). SIGNIFICANCE: Muscle volume loss may progress in parallel with MAAT accumulation, impacting contractile performance in individuals with DPN. Only 48.5% of the DPN intrinsic foot muscle compartment consists of normal muscle and greater abnormal muscle is associated with worse foot function. These changes identify an important target for rehabilitative intervention to slow or prevent muscle deterioration and poor foot outcomes.

A radiomics-based nomogram may be useful for predicting telomerase reverse transcriptase promoter mutation status in adult glioblastoma.

BACKGROUND AND PURPOSE: As a crucial diagnostic and prognostic biomarker, telomerase reverse transcriptase (TERT) promoter mutation holds immense significance for personalized treatment of patients with glioblastoma (GBM). In this study, we developed a radiomics nomogram to determine the TERT promoter mutation status and assessed its prognostic efficacy in GBM patients. METHODS: The study retrospectively included 145 GBM patients. A comprehensive set of 3736 radiomics features was extracted from preoperative magnetic resonance imaging, including T2-weighted imaging, T1-weighted imaging (T1WI), contrast-enhanced T1WI, and fluid-attenuated inversion recovery. The construction of the radiomics model was based on integrating the radiomics signature (rad-score)with clinical features. Receiver-operating characteristic curve analysis was employed to evaluate the discriminative ability of the prediction model, and the risk score was used to stratify patient outcomes. RESULTS: The least absolute shrinkage and selection operator classifier identified 10 robust features for constructing the prediction model, and the radiomics nomogram exhibited excellent performance in predicting TERT promoter mutation status, with area under the curve values of.906 (95% confidence interval [CI]:.850-.963) and.899 (95% CI:.708-.966) in the training and validation sets, respectively. The clinical utility of the radiomics nomogram is further supported by calibration curve and decision curve analyses. Additionally, the radiomics nomogram effectively stratified GBM patients with significantly different prognoses (HR = 1.767, p = .019). CONCLUSION: The radiomics nomogram holds promise as a modality for evaluating TERT promoter mutations and prognostic outcomes in patients with GBM.

Tirzepatide protects against doxorubicin-induced cardiotoxicity by inhibiting oxidative stress and inflammation via PI3K/Akt signaling.

BACKGROUND: Doxorubicin (DOX) is a highly effective and widely used cytotoxic agent with application for various malignancies, but it's clinically limited due to its cardiotoxicity Oxidative stress and inflammation were reported to take part in DOX-induced cardiotoxicity. Tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist has been approved to treat type 2 diabetes. However, its role in DOX-induced cardiotoxicity and the underlying mechanisms has not been explored. METHODS: The cardioprotective properties of Tirzepatide against DOX-induced cardiotoxicity are examined in this work both in vivo and in vitro. For four weeks, an intraperitoneal injection of 4 mg/kg DOX was used to cause cardiotoxicity in C57BL/6 mice. To ascertain the cardioprotective function and underlying mechanisms of Tirzepatide against DOX-induced cardiotoxicity, mice and H9c2 cells were treated with and without Tirzepatide. RESULTS: Tirzepatide treatment significantly inhibited DOX-induced oxidative stress, inflammation and cardiac injury. Mechanistically, PI3K/Akt signaling pathway contributes to the protective effect of Tirzepatide against DOX-induced cardiotoxicity and inhibited PI3K/Akt signaling pathway with LY294002 almost blocked its therapeutic effect. CONCLUSIONS: Collectively, Tirzepatide could alleviate DOX-induced oxidative stress, inflammation and cardiac injury via activating PI3K/Akt signaling pathway and Tirzepatide may be a novel therapeutic target for DOX-induced cardiotoxicity.

Relationships between body image, dyadic coping and post-traumatic growth in breast cancer patients: a cross-sectional study.

Background: The diagnosis and treatment of cancer triggers not only a negative psychological response for the patient, but also a positive psychological outcome. Positive dyadic coping, as a form of coping for mental health outcomes, can maintain or reestablish internal stability between the patient and his or her spouse, resulting in positive physical and psychological changes. However, there is a paucity of research on body image, dyadic coping, and post-traumatic growth in breast cancer patients. The purpose of this study was to explore the relationship and pathways between body image, dyadic coping, and post-traumatic growth in breast cancer patients. Methods: A cross-sectional study was conducted from November 2022 to November 2023 at a tertiary care hospital in Wuxi, Jiangsu, China. This study was conducted among 154 breast cancer patients treated at the Affiliated Hospital of Jiangnan University, all of whom completed demographic and clinical information questionnaires, Body image self-rating questionnaire for breast cancer (BISQ-BC), Dyadic Coping Inventory (DCI) and Post Traumatic Growth Inventory (PTGI). A Pearson correlation analysis was used to explore the relationship between body image, dyadic coping, and post-traumatic growth. Structural equation modeling was used to analyze the path relationships among the three and to explore the mediating role of dyadic coping. Results: The level of body image was negatively correlated with post-traumatic growth (r = -0.462, p < 0.01); and the level of body image was negatively correlated with dyadic coping (r = -0.308, p < 0.01). And dyadic coping was positively associated with post-traumatic growth (r = 0.464, p < 0.01). The structural equation modeling results supported the mediation model with the following model fit indices, chi-square to degrees of freedom ratio (χ2/df = 2.05), goodness of fit index (GFI = 0.93), comparative fit index (CFI = 0.99), canonical fit index (NFI = 0.93), incremental fit index (IFI = 0.99), non-canonical fit index (TLI = 0.99) and the root mean square of the difference in approximation error (RMSEA = 0.03). Body image and dyadic coping directly affected post-traumatic growth (ß = -0.33, p < 0.05; ß = 0.43, p < 0.05). And body image indirectly influenced post-traumatic growth through dyadic coping (ß = -0.17, p < 0.05). Conclusion: Interconnections between body image, dyadic coping, and post-traumatic growth in breast cancer patients. A preliminary validation of the mediating role of dyadic coping between body image and post-traumatic growth, body image can have an impact on dyadic coping, which in turn can have an impact on post-traumatic growth. Whereby higher levels of dyadic coping in patients may also be associated with higher levels of post-traumatic growth, whereas body image disturbance may impede levels of post-traumatic growth.