Development and validation of a point-of-care nursing mobile tool to guide the diagnosis of malnutrition in hospitalized adult patients: a multicenter, prospective cohort study.

Malnutrition is a prevalent and severe issue in hospitalized patients with chronic diseases. However, malnutrition screening is often overlooked or inaccurate due to lack of awareness and experience among health care providers. This study aimed to develop and validate a novel digital smartphone-based self-administered tool that uses facial features, especially the ocular area, as indicators of malnutrition in inpatient patients with chronic diseases. Facial photographs and malnutrition screening scales were collected from 619 patients in four different hospitals. A machine learning model based on back propagation neural network was trained, validated, and tested using these data. The model showed a significant correlation (p < 0.05) and a high accuracy (area under the curve 0.834-0.927) in different patient groups. The point-of-care mobile tool can be used to screen malnutrition with good accuracy and accessibility, showing its potential for screening malnutrition in patients with chronic diseases.

Prediction of a two-dimensional high Curie temperature Weyl nodal line kagome semimetal.

Kagome lattices may have numerous exotic physical properties, such as stable ferromagnetism and topological states. Herein, combining the particle swarm structure search method with first-principles calculations, we identify a two-dimensional (2D) kagome Mo2Se3 crystal structure with space group P6/mmm. The results show that 2D kagome Mo2Se3 is a 100% spin-polarized topological nodal line semimetal and exhibits excellent ambient stability. The band crossing points form two nodal loops around the high-symmetry points Γ and K. On the other hand, Mo2Se3 shows intrinsic ferromagnetism with a large magnetic moment of 3.05 µB per Mo atom and magnetic anisotropy energy (MAE) of 4.78 meV. Monte Carlo simulations estimate that Mo2Se3 possesses a high Curie temperature of about 673 K. In addition, its ferromagnetic ground state can be well preserved under external strain, and the MAE can be improved by increasing the strain. More importantly, the position of each nodal line can be adjusted to the Fermi level through hole doping. This multifunctional 2D magnetic material that combines spin and topology has great potential in the field of nanoscale spintronic devices.

Integrative models of histopathological images and multi-omics data predict prognosis in endometrial carcinoma.

Objective: This study aimed to predict the molecular features of endometrial carcinoma (EC) and the overall survival (OS) of EC patients using histopathological imaging. Methods: The patients from The Cancer Genome Atlas (TCGA) were separated into the training set (n = 215) and test set (n = 214) in proportion of 1:1. By analyzing quantitative histological image features and setting up random forest model verified by cross-validation, we constructed prognostic models for OS. The model performance is evaluated with the time-dependent receiver operating characteristics (AUC) over the test set. Results: Prognostic models based on histopathological imaging features (HIF) predicted OS in the test set (5-year AUC = 0.803). The performance of combining histopathology and omics transcends that of genomics, transcriptomics, or proteomics alone. Additionally, multi-dimensional omics data, including HIF, genomics, transcriptomics, and proteomics, attained the largest AUCs of 0.866, 0.869, and 0.856 at years 1, 3, and 5, respectively, showcasing the highest discrepancy in survival (HR = 18.347, 95% CI [11.09-25.65], p < 0.001). Conclusions: The results of this experiment indicated that the complementary features of HIF could improve the prognostic performance of EC patients. Moreover, the integration of HIF and multi-dimensional omics data might ameliorate survival prediction and risk stratification in clinical practice.

Metabolic reprogramming in cancer: Mechanisms and therapeutics.

Cancer cells characterized by uncontrolled growth and proliferation require altered metabolic processes to maintain this characteristic. Metabolic reprogramming is a process mediated by various factors, including oncogenes, tumor suppressor genes, changes in growth factors, and tumor-host cell interactions, which help to meet the needs of cancer cell anabolism and promote tumor development. Metabolic reprogramming in tumor cells is dynamically variable, depending on the tumor type and microenvironment, and reprogramming involves multiple metabolic pathways. These metabolic pathways have complex mechanisms and involve the coordination of various signaling molecules, proteins, and enzymes, which increases the resistance of tumor cells to traditional antitumor therapies. With the development of cancer therapies, metabolic reprogramming has been recognized as a new therapeutic target for metabolic changes in tumor cells. Therefore, understanding how multiple metabolic pathways in cancer cells change can provide a reference for the development of new therapies for tumor treatment. Here, we systemically reviewed the metabolic changes and their alteration factors, together with the current tumor regulation treatments and other possible treatments that are still under investigation. Continuous efforts are needed to further explore the mechanism of cancer metabolism reprogramming and corresponding metabolic treatments.

Straight and twisted open nodal-line phonon states in the CaI2 family of materials.

Based on first-principles calculations and symmetry analysis, we propose that trigonal CaI2 with the space group P3̄m1 possesses straight and twisted open nodal-line phonon states with linear dispersion. The symmetry analysis indicates that joint symmetry PT and rotational symmetry C3z protect the straight nodal lines along Γ-A and K-H while PT and mirror symmetry M010 (M110) maintain the twisted nodal lines that traverse Γ-M (Γ-K) and A-L (A-H). The calculated π Berry phase suggests that all the nodal lines are nontrivial and the corresponding drumhead-like surface states are clearly visible in the observation window, which is less than 6 THz, suggesting a significant chance for them to be measured using meV-resolution inelastic X-ray scattering. The distribution of the nodal lines in the Brillouin zone is also confirmed by the phononic tight-binding model. Furthermore, the isostructural compounds MgBr2 and MgI2 show similar phonon spectra and topological nontrivial surface states. This work provides promising candidates for investigating straight and twisted open nodal-line phonon states in a single material, which will facilitate future experimental observation.

An Overview of the Therapeutic Strategies for the Treatment of Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a recessive, neurodegenerative disorder. It is one of the most common genetic causes of infant mortality and is characterized by muscle weakness, loss of ambulation, and respiratory failure. SMA is primarily caused by a homozygous deletion or mutation of the survival motor neuron 1 (SMN1) gene. Humans possess a second, nearly identical copy of SMN, known as the SMN2 gene. Although the disease severity correlates inversely with the number of SMN2 copies present, it can never completely compensate for the loss of SMN1 in patients with SMA; SMN2 expresses only a fraction of the functional SMN transcript. The SMN protein is ubiquitous in human cells and plays several roles, ranging from assembling the spliceosome machinery to autophagy, RNA metabolism, signal transduction, cellular homeostasis, DNA repair, and recombination. Although the underlying mechanism remains unclear, anterior horn cells of the spinal cord gray matter are highly vulnerable to decreased SMN protein levels. To harness SMN2's ability to provide SMN function, two treatment strategies have been approved by the Food and Drug Administration (FDA), including an antisense oligonucleotide, nusinersen (Spinraza), and a small molecule, risdiplam (Evrysdi). Onasemnogene abeparvovec (Zolgensma) is an FDA-approved adeno-associated virus 9-mediated gene replacement therapy that creates a copy of the human SMN1 gene. In this review, we summarize the SMA etiology and FDA-approved therapies, and discuss the development of SMA therapeutic strategies and the challenges we faced.

Description of CRISPR-Cas9 development and its prospects in human papillomavirus-driven cancer treatment.

Human papillomaviruses (HPVs) have been recognized as the etiologic agents of various cancers and are called HPV-driven cancers. Concerning HPV-mediated carcinogenic action, gene therapy can cure cancer at the molecular level by means of the correction of specific genes or sites. CRISPR-Cas9, as a novel genetic editing technique, can correct errors in the genome and change the gene expression and function in cells efficiently, quickly, and with relative ease. Herein, we overviewed studies of CRISPR-mediated gene remedies for HPV-driven cancers and summarized the potential applications of CRISPR-Cas9 in gene therapy for cancer.

The role of cancer-associated mesothelial cells in the progression and therapy of ovarian cancer.

Ovarian cancer is currently one of the most common malignant tumors in females with poor survival rates around the world, killing about 200,000 women each year. Although great progress has been made in treatment, most patients receiving first-line therapy experience tumor recurrence. The tumor microenvironment plays an important role in regulating the progression and prognosis of ovarian cancer. Cancer-associated mesothelial cells are the main cell population in the tumor microenvironment, which affect the progression, prognosis and chemical resistance of ovarian cancer. Cancer-associated mesothelial cells can also interact with other microenvironmental components, such as exosomes, macrophages, and adipocytes. Some studies have developed drugs targeting cancer-associated mesothelial cells in ovarian cancer to evaluate the therapeutic efficiency. In this review we highlighted the key role of cancer-associated mesothelial cells in the progression and prognosis of ovarian cancer. We also described the progress of cancer-associated mesothelial cells targeted therapy for ovarian cancer. Continued insight into the role of cancer-associated mesothelial cells in ovarian cancer will potentially contribute to the development of new and effective therapeutic regiments.

Genetic Predisposition of Anti-Cytomegalovirus Immunoglobulin G Levels and the Risk of 9 Cardiovascular Diseases.

Background: Accumulating evidence has indicated that persistent human cytomegalovirus (HCMV) infection is associated with several cardiovascular diseases including atherosclerosis and coronary artery disease. However, whether there is a causal association between the level of anti-HCMV immune response and the risk of cardiovascular diseases remains unknown. Methods: Single-nucleotide polymorphisms associated with anti-cytomegalovirus immunoglobulin (Ig) G levels were used as instrumental variables to estimate the causal effect of anti-cytomegalovirus IgG levels on 9 cardiovascular diseases (including atrial fibrillation, coronary artery disease, hypertension, heart failure, peripheral artery disease, pulmonary embolism, deep vein thrombosis of the lower extremities, rheumatic valve diseases, and non-rheumatic valve diseases). For each cardiovascular disease, Mendelian randomization (MR) analyses were performed. Inverse variance-weighted meta-analysis (IVW) with a random-effects model was used as a principal analysis. In addition to this, the weighted median approach and MR-Egger method were used for further sensitivity analysis. Results: In the IVW analysis, genetically predicted anti-cytomegalovirus IgG levels were suggestively associated with coronary artery disease with an odds ratio (OR) of 1.076 [95% CI, 1.009-1.147; p = 0.025], peripheral artery disease (OR 1.709; 95% CI, 1.039-2.812; p = 0.035), and deep vein thrombosis (OR 1.002; 95% CI, 1.000-1.004; p = 0.025). In the further analysis, similar causal associations were obtained from weighted median analysis and MR-Egger analysis with lower precision. No notable heterogeneities and horizontal pleiotropies were observed (p > 0.05). Conclusions/Interpretation: Our findings first provide direct evidence that genetic predisposition of anti-cytomegalovirus IgG levels increases the risk of coronary artery disease, peripheral artery disease, and deep vein thrombosis.

Small cell lung cancer transformation: From pathogenesis to treatment.

Small cell lung cancer (SCLC) is a type of neuroendocrine tumor with high malignancy and poor prognosis. Besides the de novo SCLC, there is transformed SCLC, which has similar characteristics of pathological morphology, molecular characteristics, clinical manifestations and drug sensitivity. However, de novo SCLC and transformed SCLC have different pathogenesis and tumor microenvironment. SCLC transformation is one of the mechanisms of resistance to chemotherapy, immunotherapy, and targeted therapy in NSCLC. Two hypotheses have been used to explain the pathogenesis of SCLC transformation. Although SCLC transformation is not common in clinical practice, it has been repeatedly identified in many small patient series and case reports. It usually occurs in epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma after treatment with tyrosine kinase inhibitors (TKIs). SCLC transformation can also occur in anaplastic lymphoma kinase (ALK)-positive lung cancer after treatment with ALK inhibitors and in wild-type EGFR or ALK NSCLC treated with immunotherapy. Chemotherapy was previously used to treat transformed SCLC, yet it is associated with an unsatisfactory prognosis. We comprehensively review the advancements in transformed SCLC, including clinical and pathological characteristics, and the potential effective treatment after SCLC transformation, aiming to give a better understanding of transformed SCLC and provide support for clinical uses.

Criteria for judging the immune markers of COVID-19 disease vaccines.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sweeping the world, effective and affordable vaccines are in urgent need. A reliable system for the assessment of SARS-CoV-2 vaccines would boost the development of vaccines and reduce the research cost. We constructed a logistic regression model and analyzed the relationship between antibody (Ab) level and efficacy of different vaccine types. The relationship between assessment dates and Ab levels was depicted by plotting the mean of Ab levels evolved over time and a fitted cubic polynomial model. Anti-spike immunoglobulin G (IgG) could best estimate the vaccine efficacy (VE) (adjusted R 2  = 0.731) and neutralizing Ab to live SARS-CoV-2 also explained a fine relationship (adjusted R 2 = 0.577). Neutralizing Abs to live SARS-CoV-2 in inactivated virus vaccines reached a peak during days 40-60, and their receptor-binding domain (RBD)-IgG peaked during days 40-50. For messenger RNA (mRNA) and viral vector vaccines, their neutralizing Ab to live SARS-CoV-2 peaked later than day 40, and for RBD-IgG during days 30-50. For mRNA and viral vector vaccines, their peak time of Abs was later than that in inactivated virus vaccines. RBD-IgG peaked earlier than Ab to live SARS-CoV-2. Anti-spike IgG and Ab to live SARS-CoV-2 may be good immune markers for VE assessment.

Impact of resistance exercise rehabilitation and whey protein supplementation in elderly patients with heart failure with preserved ejection fraction with sarcopenia: a study protocol for a randomised controlled trial.

INTRODUCTION: Heart failure with preserved ejection fraction (HFpEF) affects more than half of the patients with heart failure. HFpEF and sarcopenia can interact with each other and contribute to reduced physiological function and increased mortality in elderly patients. Resistance training (RT) or resistance exercise rehabilitation (RER) may have benefits for elderly HFpEF patients with sarcopenia. Whey protein supplementation (WPS) may increase the effects of exercise on strength and muscle mass, in addition to promoting heart function and quality of life (QoL). However, studies are needed to evaluate effects of RER and WPS in patients with HFpEF with sarcopenia. METHODS AND ANALYSIS: This is a prospective, randomised, controlled clinical trial in which patients with HFpEF with sarcopenia will be randomly allocated to three groups, control, RT and RT+WP. Participants in all groups will receive basic intervention including standard medicine treatment, home-based aerobic exercise and basic nutritional intervention. The RT group will undergo resistance exercise programmes, and the RT+WP group will receive daily WPS apart from resistance exercise. The study variables will be evaluated at baseline and 12 weeks. Primary outcome measure is the change of 6 min walking distance. Secondary outcomes include parameters of muscle status, cardiac function, nutritional status, QoL and major adverse cardiovascular events. The primary efficacy analysis will follow the intention-to-treat principle. ETHICS AND DISSEMINATION: This study was approved by Ethics Committee of China-Japan Friendship Hospital for Clinical Research (No. 2022-KY-003). The results of this study will be disseminated via peer-reviewed publications and presentations at conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200061069.

Ion release behavior of vanadium-doped mesoporous bioactive glass particles and the effect of the released ions on osteogenic differentiation of BMSCs via the FAK/MAPK signaling pathway.

Vanadium is an important trace element in bone and is involved in bone metabolism, bone formation, and bone growth, but the roles of various vanadium ions, especially of pentavalent vanadium, in bone tissue regenerative repair have been underestimated and even misinterpreted for a long time. The main purposes of this study are to investigate the release profile of Si, Ca, P, and V ions from vanadium doped mesoporous bioactive glass (V-MBG) particles and to explore the effect of pentavalent vanadium ions on proliferation and osteogenic differentiation of BMSCs as well as the corresponding osteogenic signaling pathway. On the basis of preparations of V-MBG particles with different pentavalent vanadium contents, the ion release behavior from V-MBG in distilled water and simulated body fluid was systemically investigated. Furthermore, the cytocompatibility and osteogenic effect of V-MBG extracts were studied in rBMSCs, and the related molecular mechanisms were preliminarily discussed. The results of dissolution experiments showed that the V ionic concentration exhibited a burst increase and then a sustained slow increase in the two media. The resultant V ions from 1.0V-MBG, 4.0V-MBG and 10.0V-MBG at 21 days were about 1.1, 5.8, and 12.5 mg L-1 in water, respectively, and 1.6, 4.8 and 12.8 mg L-1 in SBF, respectively. The release behaviors of Si, Ca, P, and V ions were evidently affected by high contents of incorporated vanadium. The cellular results indicated that compared to the control and MBG groups, the V(V) ions in V-MBG extracts at about 19.4 µM markedly promoted the proliferation, the gene and protein expression of BMP-2 and COL-I, and the ALP activity of rBMSCs in non-osteoinductive media, but insignificantly stimulated the OCN protein synthesis. More deeply, V(V) ions at about 19.4 µM significantly upregulated the gene and protein expressions of Itga 2b, FAK, and pERK1/2, demonstrating that V(V) ions could regulate osteogenic differentiation of rBMSCs through the activation of the Itga 2b-FAK-MAPK (pERK1/2) signaling pathway. The in vivo results further confirmed that V-MBG induced and promoted new bone formation in the defect area compared to the PGC and PGC/V-M0 groups. These results would contribute to modify the perception about the biocompatibility and osteogenic promotion of pentavalent vanadium at an appropriate concentration.

Author Correction: miR-20a suppresses chondrogenic differentiation of ATDC5 cells by regulating Atg7.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

miR-20a suppresses chondrogenic differentiation of ATDC5 cells by regulating Atg7.

Both the miR-17-92 cluster and autophagy have been suggested as critical regulators of bone development, but the potential correlation between the two factors is largely unknown. Hence, we investigated whether members of this cluster can regulate chondrogenesis through an autophagy-related signalling pathway. In this study, the expression of miR-17-92 cluster members and the level of autophagic activity were investigated during chondrogenic induction in ATDC5 cells. miR-17, miR-18a, miR-20a, and miR-92-1 showed significant changes, and the level of autophagic activity was enhanced. Among the miR-17-92 cluster members, miR-20a showed the most significant change. Histological, cellular and molecular analyses were performed after the regulation of miR-20a and autophagy. miR-20a and autophagy had the opposite effect on chondrogenic differentiation, and there was a negative correlation between them. Moreover, the expression of the autophagy regulatory gene Atg7 was inhibited by miR-20a. siRNA was then used to knock down Atg7, and the results further indicated that Atg7 might be a potential target of miR-20a in chondrogenic differentiation. In conclusion, miR-20a is a critical negative regulator of chondrogenic differentiation because it inhibits autophagy via Atg7. Other members of the miR-17-92 cluster may have a similar effect, but this hypothesis requires further investigation.

Dynamic Nasolabial Growth After Primary Surgery for Patients With Bilateral Cleft Lip: A Five-Year Follow-Up Study.

PURPOSE: Bilateral complete cleft lip (BCCL) causes severe tissue deficit and usually requires multiple revisions after primary repair. In the present study, we aimed to illustrate the nasolabial changes after primary BCCL correction. PATIENTS AND METHODS: The present retrospective cohort study compared patients who had undergone BCCL and palate (BCCLP) and cleft palate only (CPO). All included patients had undergone surgery at the same treatment center (West China Hospital of Stomatology) from 2007 to 2012. The patients returned for follow-up surgery at 6 months and 5 years after their primary repair surgery. We retrieved the facial plaster casts of the enrolled patients and recorded the key nasolabial measurements. The outcome variables included the prolabial length (PL), peak distance, nasal width, and columellar length (CL). The data were analyzed using a general linear model for repeated measures, and the linear association was tested using SPSS. The level of testing efficiency (P value) was set at .05. RESULTS: A total of 160 patients, 80 who had undergone BCCLP and 80 CPO controls, were included. All nasolabial measurements in the BCCLP group had increased during the 5-year follow-up period. The PL of the BCCLP group had increased more quickly than the PL of the CPO group (P = .000 < .05), but the CL had increased nearly as much (P = .270). CONCLUSIONS: For the primary correction of bilateral cleft lip nose deformity, dissection and repositioning of the cleft lip and nose did not significantly inhibit the growth of the nasolabial region in the first 5 years after surgery. Nose deformities should not remain uncorrected after primary surgical repair. In contrast, cleft surgeons should focus on the finer adjustment of columella with less doubt regarding adverse effects.

Analysis of Velopharyngeal Functions Using Computational Fluid Dynamics Simulations.

OBJECTIVES: Competent velopharyngeal (VP) function is the basis for normal speech. Understanding how VP structure influences the airflow during speech details is essential to the surgical improvement of pharyngoplasty. In this study, we aimed to illuminate the airflow features corresponding to various VP closure states using computed dynamic simulations. METHODS: Three-dimensional models of the upper airways were established based on computed tomography of 8 volunteers. The velopharyngeal port was simulated by a cylinder. Computational fluid dynamics simulations were applied to illustrate the correlation between the VP port size and the airflow parameters, including the flow velocity, pressure in the velopharyngeal port, as well as the pressure in oral and nasal cavity. RESULTS: The airflow dynamics at the velopharynx were maintained in the same velopharyngeal pattern as the area of the velopharyngeal port increased from 0 to 25 mm2. A total of 5 airflow patterns with distinct features were captured, corresponding to adequate closure, adequate/borderline closure (Class I and II), borderline/inadequate closure, and inadequate closure. The maximal orifice area that could be tolerated for adequate VP closure was determined to be 2.01 mm2. CONCLUSION: Different VP functions are of characteristic airflow dynamic features. Computational fluid dynamic simulation is of application potential in individualized VP surgery planning.

Identification of two candidate innate immune genes by transcriptional profiling and RNA interference in mouse mammary gland epithelial cells stimulated with lipopolysaccharide.

Mammary epithelial cells (MECs) play an important role in immune responses and inflammatory diseases such as mastitis, which is mainly attributed to the activation of Toll-like receptors and the release of cytokines. However, the overall change of gene expression and biological pathways of MECs to microbial factors stimulation remains unknown. Here, we analyzed the gene expression profile in mouse MECs treated with lipopolysaccharide (LPS) for 24 h. Microarray analysis revealed that about 1548 genes differentially expressed, these genes mainly involved in 346 gene ontology terms and 128 molecular pathways, and particularly, some innate immune-associated pathways were significant. By analyzing data for pathway relation network, we prioritized differentially expressed genes with respect to LPS. The importance of changes, indicating that RNA interference-mediated inhibition of two genes identified in this analysis, transforming growth factor beta 1 (Tgf-ß1) and platelet-derived growth factor B (Pdgfb), reduced interleukin (IL)-6 and tumor necrosis factor α production respectively, in gene expression was verified. These findings delineate mouse MECs gene response patterns induced by LPS and identify Tgf-ß1 and Pdgfb that have been closely related to innate immunity.