Assessing Surgical Benefits and Creating a Prognostic Model for Breast Cancer with Lung-only Metastasis: An Analysis of the National Cancer Database.

AIM: The decision to perform surgery on breast cancer patients with lung-only metastasis is a subject of ongoing debate. Our investigation seeks to assess the survival rates following surgical intervention among individuals diagnosed with breast cancer experiencing isolated metastasis to the lungs. Additionally, we endeavor to devise a predictive nomogram aimed at forecasting the long-term survival. METHODS: We analyzed patients diagnosed with primary lung metastases from breast cancer between 2010 and 2015, utilizing datasets obtained from the National Cancer Database (NCDB). We employed the Cox proportional hazards regression model and the Kaplan-Meier method to analyze survival data. Additionally, we constructed nomograms to forecast survival outcomes. RESULTS: The study comprised 2403 patients, with 1058 (44.0%) undergoing breast-specific surgery and 1345 (56.0%) not receiving surgical treatment. The group that underwent surgical procedures exhibited a significantly enhanced overall survival (OS) compared to the non-surgery group (multivariate analysis: hazard ratio [HR] = 0.64; 95% confidence interval [CI], 0.54-0.75; p < 0.001). Surgical intervention consistently improved survival across nearly all patient subgroups. The research successfully established a predictive nomogram designed to calculate the likelihood of long-term survival, attaining a concordance index (C-index) of approximately 0.7 in both validation and training cohorts. By integrating multiple clinicopathological variables, the nomogram efficiently classified patients into categories reflecting different survival forecasts. CONCLUSIONS: The findings of this investigation support the notion that surgical treatment can enhance the overall survival of patients with initial lung-only metastasis from breast cancer. The investigation further introduces a nomogram demonstrating reasonable accuracy in forecasting long-term survival of patients in this cohort.

Cathepsin K deficiency prevented stress-related thrombosis in a mouse FeCl3 model.

BACKGROUND: Exposure to chronic psychological stress (CPS) is a risk factor for thrombotic cardiocerebrovascular diseases (CCVDs). The expression and activity of the cysteine cathepsin K (CTSK) are upregulated in stressed cardiovascular tissues, and we investigated whether CTSK is involved in chronic stress-related thrombosis, focusing on stress serum-induced endothelial apoptosis. METHODS AND RESULTS: Eight-week-old wild-type male mice (CTSK+/+) randomly divided to non-stress and 3-week restraint stress groups received a left carotid artery iron chloride3 (FeCl3)-induced thrombosis injury for biological and morphological evaluations at specific timepoints. On day 21 post-stress/injury, the stress had enhanced the arterial thrombi weights and lengths, in addition to harmful alterations of plasma ADAMTS13, von Willebrand factor, and plasminogen activation inhibitor-1, plus injured-artery endothelial loss and CTSK protein/mRNA expression. The stressed CTSK+/+ mice had increased levels of injured arterial cleaved Notch1, Hes1, cleaved caspase8, matrix metalloproteinase-9/-2, angiotensin type 1 receptor, galactin3, p16IN4A, p22phox, gp91phox, intracellular adhesion molecule-1, TNF-α, MCP-1, and TLR-4 proteins and/or genes. Pharmacological and genetic inhibitions of CTSK ameliorated the stress-induced thrombus formation and the observed molecular and morphological changes. In cultured HUVECs, CTSK overexpression and silencing respectively increased and mitigated stressed-serum- and H2O2-induced apoptosis associated with apoptosis-related protein changes. Recombinant human CTSK degraded γ-secretase substrate in a dose-dependent manor and activated Notch1 and Hes1 expression upregulation. CONCLUSIONS: CTSK appeared to contribute to stress-related thrombosis in mice subjected to FeCl3 stress, possibly via the modulation of vascular inflammation, oxidative production and apoptosis, suggesting that CTSK could be an effective therapeutic target for CPS-related thrombotic events in patients with CCVDs.

Changes in long-term care insurance revenue among service providers during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has impacted peoples' health-related behaviors, especially those of older adults, who have restricted their activities in order to avoid contact with others. Moreover, the pandemic has caused concerns in long-term care insurance (LTCI) providers regarding management and financial issues. This study aimed to examine the changes in revenues among LTCI service providers in Japan during the pandemic and analyze its impact on different types of services. METHODS: In this study, we used anonymized data from "Kaipoke," a management support platform for older adult care operators provided by SMS Co., Ltd. Kaipoke provides management support services to more than 27,400 care service offices nationwide and has been introduced in many home-care support offices. The data used in this study were extracted from care plans created by care managers on the Kaipoke platform. To examine the impact of the pandemic, an interrupted time-series analysis was conducted in which the date of the beginning of the pandemic was set as the prior independent variable. RESULTS: The participating providers were care management providers (n = 5,767), home-visit care providers (n = 3,506), home-visit nursing providers (n = 971), and adult day care providers (n = 4,650). The results revealed that LTCI revenues decreased significantly for care management providers, home-visit nursing providers, and adult day care providers after the COVID-19 pandemic began. The largest decrease was an average base of USD - 1668.8 in adult day care. CONCLUSION: The decrease in revenue among adult day care providers was particularly concerning in terms of the sustainability of their business. This decrease in revenue may have made it difficult to retain personnel, and staff may have needed to be laid off as a result. Although this study has limitations, it may provide useful suggestions for countermeasures in such scenarios, in addition to support conducted measures.

SbMYC2 mediates jasmonic acid signaling to improve drought tolerance via directly activating SbGR1 in sorghum.

KEY MESSAGE: SbMYC2 functions as a key regulator under JA signaling in enhancing drought tolerance of sorghum through direct activating SbGR1. Drought stress is one of the major threats to crop yield. In response to drought stress, functions of basic helix-loop-helix (bHLH) transcription factors (TFs) have been reported in Arabidopsis and rice, but little is known for sorghum. Here, we characterized the function of SbMYC2, a bHLH TF in sorghum, and found that SbMYC2 responded most significantly to PEG-simulated drought stress and JA treatments. Overexpression of SbMYC2 significantly enhanced drought tolerance in Arabidopsis, rice and sorghum. In addition, it reduced reactive oxygen species (ROS) accumulation and increased chlorophyll content in sorghum leaves. While silencing SbMYC2 by virus-induced gene silencing (VIGS) resulted in compromised drought tolerance of sorghum seedlings. Moreover, SbMYC2 can directly activate the expression of GLUTATHIONE-DISULFIDE REDUCTASE gene SbGR1. SbGR1 silencing led to significantly weakened drought tolerance of sorghum, and higher ROS accumulation and lower chlorophyll content in sorghum leaves were detected. In addition, SbMYC2 can interact with SbJAZs, suppressors of JA signaling, and thus can mediate JA signaling to activate SbGR1, thereby regulating sorghum's tolerance to drought stress. Overall, our findings demonstrate that bHLH TF SbMYC2 plays an important role in sorghum's response to drought stress, thus providing one theoretical basis for genetic enhancement of sorghum and even rice.

Development of a short form of the Japanese version of the Caregiver Reaction Assessment (CRA-J-10) among informal caregivers of older adults.

AIM: To support informal caregivers, a simple assessment tool capturing the multidimensional nature of caregiving experiences, including negative and positive aspects, is required. We developed a short form of the Japanese version of the Caregiver Reaction Assessment (CRA-J), a multidimensional assessment scale for caregiver experiences. METHODS: The internet survey involved 934 Japanese informal caregivers aged 20-79 years (mean age = 58.8 years; 50.2% women) who completed questionnaires, including the CRA-J 18 items (CRA-J-18), consisting of five domains, such as impacts on schedule and finances and positive experiences of caregiving. A 10-item short version of the CRA-J (CRA-J-10; 0-50 points), which was prepared by selecting the two items with the highest factor loadings from each domain, was tested for model fit by confirmatory factor analysis (CFA) and was analyzed for correlations with the CRA-J-18, Zarit Burden Interview (ZBI), Positive Aspects of Caregiving Scale (PACS), Patient Health Questionnaire-9 (PHQ-9), and WHO-Five Well-Being Index (WHO-5). The area under the curve (AUC) in the receiver operating characteristic was evaluated as discriminability for depressive symptoms (PHQ-9 ≥ 10 points). RESULTS: The CFA indicated a good model fit in the CRA-J-10. The CRA-J-10 correlated well with the CRA-J-18 and other variables (CRA-J-18, r = 0.970; ZBI, r = 0.747; PACS, r = -0.467; PHQ-9, r = 0.582; WHO-5, r = -0.588) and showed good discriminant performance for the presence of depressive symptoms (AUC = 0.793, 95% confidence interval = 0.762-0.823). CONCLUSIONS: The CRA-J-10 allows a simple assessment of caregiver experiences, helping support informal caregivers. Geriatr Gerontol Int 2024; 24: 290-296.

Recurrent syncope driven by unique-variant angina pectoris.

The patient's vasospastic variant angina manifested as syncope with asymptomatic ischemic episodes, and repeated 24-h dynamic electrocardiogram and coronary angiography examinations combined with coronary provocation spasm tests were necessary for its diagnosis and management.

Decision-making involvement and onset of cognitive impairment in community-dwelling older care recipients: a 2-year longitudinal study.

BACKGROUND: The decision-making of older adults and people with dementia is attracting more attention among healthcare professionals. While cognitive impairment has been examined as a factor related to decision-making, it can also be assumed that involvement in decision-making leads to the maintenance of cognitive function. This study examined the association of the decision-making process with the onset of cognitive impairment. METHODS: We analyzed data from a 2-year longitudinal panel survey of community-dwelling care recipients aged ≥65 years in Japan. The sample included 406 participants who responded to both baseline and follow-up surveys, were cognitively intact at baseline, and had no missing cognitive impairment data regarding onset at follow-up. The status of decision-making involvement was assessed using a single item and classified into four categories: 'very involved,' 'less involved,' 'unclear about desired care,' and 'having no one to share the decision.' RESULTS: Among the participants (women, 65.0%; ≥75 years old: 68.2%), the incidence of cognitive impairment during the follow-up was 26.6%. Multivariable logistic regression showed that, compared with highly involved participants, those who lacked clarity about desired care were more likely to develop an onset of cognitive impairment (odds ratio: 5.49; 95% confidence interval: 1.63-18.54; P = 0.006). CONCLUSION: Even among cognitively intact care recipients, those who are not able to formulate their desired care may be at risk of cognitive decline. Therefore, support for the decision-making process, not limited to the final decision, is essential to improving the prognosis of community-dwelling care recipients.

Bacillus subtilis JATP-3 Improves Nitrogen Metabolism by Regulating Intestinal Flora and AKG in Weaned Piglets.

Recently, it has been reported that oral probiotics improve the apparent digestibility of nitrogen in weaned piglets; however, the underlying mechanism is unclear. A total of 12 crossbred piglets (Yorkshire × Landrace; 28 days old) were randomly divided into two groups. The control (Con) group was fed with a basic diet + Luria-Bertani (LB; sterile; 10 mL), whereas the subject (Sub) group was fed with a basic diet + B. subtilis JATP-3 (1 × 109 CFU/mL; 10 mL). The results showed that feeding B. subtilis JATP-3 increased the final body weight and nitrogen deposition rate of weaned piglets (P < 0.05); while the daily weight gain showed an upward trend (P < 0.1). The abundance of Pedicoccus, Collinella, Turiciator, Veillonella, Clostridium, and Escherichia were significantly increased in the jejunum (P < 0.05). The abundance of Olsenella and Pediococcus were significantly increased in the ileum (P < 0.05). The metabolomics analysis showed that the levels of l-lactic acid and Alpha-ketoglutaric acid (AKG) in portal vein plasma were significantly increased (P < 0.05). In addition, the content of AKG in muscle and liver increased significantly (P < 0.01). The metagenomics analysis showed that Veillonella encoded the functional genes of 2-oxoglutarate synthase and promoted AKG production. The protein expression of eIF4E-binding protein 1 (4EBP1) phosphorylated in the skeletal muscle increased (P < 0.05). In summary, B. subtilis JATP-3 promotes dietary nitrogen metabolism and skeletal muscle synthesis by modulating the intestinal microbiota and its metabolites, in which AKG may be one of the main mediators of the therapeutic effects of B. subtilis JATP-3.

Research Progress on the Cardiotoxicity of EGFR-TKIs in Non-Small Cell Lung Cancer.

OPINION STATEMENT: With the development of molecular biology and histology techniques, targeted therapy for non-small cell lung cancer (NSCLC) has emerged, which is highly effective and has marginal side effects. Epidermal growth factor receptor (EGFR) was the first driver gene discovered, whose three generations of therapeutic use have its characteristics and benefits in clinical practice. However, cardiovascular complications by EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in preclinical studies have been increasingly reported, including heart failure, cardiomyopathy, and QT prolongation, among others. Cardiotoxicity of targeted drugs significantly affects the therapeutic effect of NSCLC and has become the second leading cause of death in NSCLC. The aim of the present review was to recognize the potential cardiotoxicity of third-generation targeted drugs in the treatment of NSCLC and their associated mechanisms to help clinicians identify and prevent it early in the treatment, minimize the cardiotoxicity of targeted drugs, and improve the therapeutic effect of patients.

Facility staffing associated with potentially avoidable hospitalizations in nursing home residents in Japan: a retrospective cohort study.

BACKGROUND: Wide variations in facility staffing may lead to differences in care, and consequently, adverse outcomes such as hospitalizations. However, few studies focused on types of occupations. Therefore, we aimed to examine the association between a wide variety of facility staffing and potentially avoidable hospitalizations of nursing home residents in Japan. METHODS: In this retrospective cohort study using long-term care and medical insurance claims data in Ibaraki Prefecture from April 2018 to March 2019, we identified individuals aged 65 years and above who were newly admitted to nursing homes. In addition, facility characteristic data were obtained from the long-term care insurance service disclosure system. Subsequently, we conducted a multivariable Cox regression analysis and evaluated the association between facility staffing and potentially avoidable hospitalizations. RESULTS: A total of 2909 residents from 235 nursing homes were included. The cumulative incidence of potentially avoidable hospitalizations at 180 days was 14.2% (95% confidence interval [CI] 12.7-15.8). Facilities with full-time physicians (adjusted hazard ratio [HR]: 0.59, 95% CI: 0.37-0.94) and a higher number of dietitians (HR: 0.72, 95% CI: 0.54-0.97) were significantly associated with a lower likelihood of potentially avoidable hospitalizations. In contrast, having nurses or trained caregivers during the night shift (HR: 1.72, 95% CI: 1.25-2.36) and a higher number of care managers (HR: 1.37, 95% CI: 1.03-1.83) were significantly associated with a high probability of potentially avoidable hospitalizations. CONCLUSIONS: We revealed that variations in facility staffing were associated with potentially avoidable hospitalizations. The results suggest that optimal allocation of human resources, such as dietitians and physicians, may be essential to reduce potentially avoidable hospitalizations. To provide appropriate care to nursing home residents, it is necessary to establish a system to effectively allocate limited resources. Further research is warranted on the causal relationship between staff allocation and unnecessary hospitalizations, considering the confounding factors.

The mRNA stability of NCAPG2, a novel contributor to breast invasive carcinoma, is enhanced by the RNA-binding protein PCBP2.

Non-SMC condensin II complex subunit G2 (NCAPG2) is one of the three non-SMC subunits in condensin II, which plays a vital role in regulating chromosome condensation and segregation. Although the tumor-promoting role of NCAPG2 has been reported in several solid malignancies, its function in breast invasive carcinoma (BRCA) remains unknown. Data both from GEPIA and GSE36295 indicated that NCAPG2 mRNA expression was abnormally upregulated in cancer tissues, which was further verified in 40 paired BRCA and para-carcinoma samples. Kaplan-Meier Plotter further illustrated that BRCA patients with higher NCAPG2 expression have a poorer prognosis. Functional experiments carried out in two BRCA cell lines (MCF-7 and T-47D) showed that NCAPG2-silenced BRCA cells acquired less aggressive behavior - weakened growth and metastasis both in vitro and in vivo. Label-free proteomics quantified the protein expression patterns in MCF-7 cells, and the results revealed 684 differentially expressed proteins (|log2FC| > 1 and P < 0.05) downstream to NCAPG2. Interestingly, poly(C)-binding protein 2 (PCBP2), an RNA binding protein previously known to increase RNA stability of its target genes, was found to directly bind to and protect NCAPG2 mRNA from degradation-PCBP2 knockdown accelerated the degradation half-life time of NCAPG2 mRNA from approximately 8 h to 5 h. Taken together, our study indicates that NCAPG2 acts as a novel contributor to BRCA growth and metastasis under the regulation of PCBP2, providing insights into BRCA treatment.

Cathepsin S activity controls chronic stress-induced muscle atrophy and dysfunction in mice.

Exposure to chronic psychological stress (CPS) is an intractable risk factor for inflammatory and metabolic diseases. Lysosomal cysteinyl cathepsins play an important role in human pathobiology. Given that cathepsin S (CTSS) is upregulated in the stressed vascular and adipose tissues, we investigated whether CTSS participates in chronic stress-induced skeletal muscle mass loss and dysfunction, with a special focus on muscle protein metabolic imbalance and apoptosis. Eight-week-old male wildtype (CTSS+/+) and CTSS-knockout (CTSS-/-) mice were randomly assigned to non-stress and variable-stress groups. CTSS+/+ stressed mice showed significant losses of muscle mass, dysfunction, and fiber area, plus significant mitochondrial damage. In this setting, stressed muscle in CTSS+/+ mice presented harmful alterations in the levels of insulin receptor substrate 2 protein content (IRS-2), phospho-phosphatidylinositol 3-kinase, phospho-protein kinase B, and phospho-mammalian target of rapamycin, forkhead box-1, muscle RING-finger protein-1 protein, mitochondrial biogenesis-related peroxisome proliferator-activated receptor-γ coactivator-α, and apoptosis-related B-cell lymphoma 2 and cleaved caspase-3; these alterations were prevented by CTSS deletion. Pharmacological CTSS inhibition mimics its genetic deficiency-mediated muscle benefits. In C2C12 cells, CTSS silencing prevented stressed serum- and oxidative stress-induced IRS-2 protein reduction, loss of the myotube myosin heavy chain content, and apoptosis accompanied by a rectification of investigated molecular harmful changes; these changes were accelerated by CTSS overexpression. These findings demonstrated that CTSS plays a role in IRS-2-related protein anabolism and catabolism and cell apoptosis in stress-induced muscle wasting, suggesting a novel therapeutic strategy for the control of chronic stress-related muscle disease in mice under our experimental conditions by regulating CTSS activity.

Lactobacillus rhamnosus GG ATCC53103 and Lactobacillus plantarum JL01 improved nitrogen metabolism in weaned piglets by regulating the intestinal flora structure and portal vein metabolites.

At present, most studies have shown that probiotics have a positive regulatory effect on the nutritional metabolism of the body, but the mechanism is still unclear. Here, 48 piglets were divided into four groups. The control group was not fed probiotics, the Lac group was fed L. Rhamnosus GG ATCC53103, the Rha group was fed L. Plantarum JL01, and the mix group was fed two types of probiotics. Nitrogen metabolism and mRNA levels of mTOR and S6K in skeletal muscle were observed in each group. Then, metagenome and non-targeted metabonomics were used to observe the changes of intestinal microorganisms and plasma metabolites in portal channels after probiotics feeding. Finally, we combined the results of omics analysis to reveal the mechanism of probiotics on nitrogen metabolism in weaned piglets. The results showed that L. Rhmnosus GG ATCC53103 and L. Plantarum JL01 increased nitrogen apparent digestibility, nitrogen deposition rate, and nitrogen utilization rate of weaned piglets (P < 0.05); the relative expression of mTOR and SK6 mRNA in skeletal muscle increased significantly (P < 0.05). When L. rhamnosus GG ATCC53103 and L. plantarum JL01 were combined, we found that Clostridium and Prevotella significantly increased in the jejunum (P < 0.05). The relative abundance of Lactobacillus, Ruminococcus, Streptococcus, and Prevotella in the ileum increased significantly (P < 0.05). Compared with the control group, L-Tryptophan, 3-Phosphonyloxypyruvate, cis-Aconitate, and Carbamoyl phosphate were significantly increased in the mixed group portal vein. The result of the combinatorial analysis showed that the significantly increased microorganisms could encode the enzyme genes for the synthesis of L-Tryptophan, 3-Phosphonooxypyruvate, cis-Aconitate, and Carbamoyl phosphate. In summary, our results demonstrated that L. Rhamnosus GG ATCC53103 and L. Plantarum JL01 could stimulate the expression of skeletal muscle protein synthesis genes of weaned piglets by modulating the structure of the gut microbiota and its metabolites, thereby improving nitrogen metabolism in weaned piglets.

PD-1/PD-L1 immune checkpoint inhibitors in metastatic triple-negative breast cancer: a systematic review and meta-analysis.

Background: PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have been controversial in the treatment of metastatic triple negative breast cancer (mTNBC). We collected randomized controlled trials in accordance with the study and carried out meta-analysis to comprehensively evaluate the efficacy and safety of immune checkpoint inhibitors in mTNBC. Aim: To systematically evaluate the efficacy and safety of PD-1/PD-L1 ICIs (hereinafter referred to as ICIs) in the treatment of mTNBC. Methods: As of 2023.2.5, Medline, PubMed, Embase, Cochrane library database and Web of Science were searched to determine the study in accordance with the trial of ICIs in the treatment of mTNBC. The assessment endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Meta-analysis of the included studies was performed using Revman 5.4. Results: A total of six trials with 3172 patients were included in this meta-analysis. The ORR of ICIs combined with chemotherapy was significantly improved compared with chemotherapy (HR=0.88, 95%CI: 0.81-0.94, I2 = 0%). For PFS, the experimental group were better than the control group in both intention-to-treat (ITT) population and PD-L1 positive population, showing statistical significance (ITT: HR=0.81, 95%CI: 0.74-0.89, P<0.05, I2 = 0%; PD-L1 positive: HR=0.72, 95%CI: 0.63-0.82, P<0.05, I2 = 18%); For OS, in the ITT population, no statistical difference was observed in either ICIs combined with chemotherapy(HR=0.92, 95%CI: 0.83-1.02, P=0.10)or immune monotherapy(HR=0.78, 95%CI: 0.44-1.36, P=0.37), in the PD-L1 positive population, ICIs group had better OS than chemotherapy group (HR=0.83, 95%CI: 0.74-0.93, P < 0.05); In safety, serious adverse event (SAE) was no statistically significant difference between the ICIs group and the chemotherapy group; however, the incidence of immune-related adverse event (irAE) was significantly higher in the ICIs group than in the chemotherapy group (HR=2.15, 95%CI: 1.45-3.19, P < 0.05). Conclusion: ICIs combined with chemotherapy significantly improved the PFS of mTNBC, however, ICIs only improved the OS in PD-L1 positive people, and no statistical difference was observed in ITT population; while benefiting from ICIs, we found that irAE in ICIs group increased significantly, and its high rate of adverse events still needs to be taken seriously.

ARHGAP25 suppresses the development of breast cancer by an ARHGAP25/Wnt/ASCL2 feedback loop.

Downregulation of ARHGAP25 was found in the tumor samples from breast cancer patients and five breast cancer cell lines. However, its precise role and molecular mechanisms in breast cancer remain completely unknown. Herein, we found that knockdown of ARHGAP25 in breast cancer cells promoted proliferation, migration and invasion of breast cancer cells. Mechanistically, ARHGAP25 silence facilitated the activation of the Wnt/ß-catenin pathway and the upregulation of its downstream molecules (including c-Myc, Cyclin D1, PCNA, MMP2, MMP9, Snail and ASCL2) by directly regulating Rac1/PAK1 in breast cancer cells. In vivo xenograft experiments indicated ARHGAP25 silence promoted tumor growth and activated the Wnt/ß-catenin pathway. In contrast, overexpression of ARHGAP25 in vitro and in vivo impeded all of the above cancer properties. Intriguingly, ASCL2, a downstream target of the Wnt/ß-catenin pathway, transcriptionally repressed the expression of ARHGAP25 and therefore constituted a negative feedback loop. Moreover, bioinformatics analysis indicated that ARHGAP25 was significantly correlated with tumor immune cell infiltration and the survival of patients with different immune cell subgroups in breast cancer. Collectively, our work revealed that ARHGAP25 suppressed tumor progression of breast cancer. It provides a novel insight for the treatment of breast cancer.

LAPTM5 regulated by FOXP3 promotes the malignant phenotypes of breast cancer through activating the Wnt/ß­catenin pathway.

Breast cancer remains the most common malignancy and the leading cause of cancer­associated mortality in women worldwide. Lysosomal protein transmembrane 5 (LAPTM5), a lysosomal membrane protein, plays an important role in several human malignancies. However, the biological functions and mechanism of LAPTM5 in breast cancer remain unclear. In the present study, the potential tumor­promoting effect of LAPTM5 was predicted by bioinformatics analysis. LAPTM5 was highly expressed in breast cancer clinical specimens. Moreover, in vitro studies demonstrated that cell proliferation, migration and invasion, as well as the process of epithelial­mesenchymal transition (EMT) were promoted by LAPTM5 overexpression and were suppressed by LAPTM5 downregulation in vitro. The tumor­promoting effects of LAPTM5 were also confirmed by xenograft tumor assay in vivo. It was found that the tumor­promoting effects of LAPTM5 were partly dependent on the activation of the Wnt/ß­catenin signaling pathway. Furthermore, dual­luciferase and chromatin immunoprecipitation assays verified that the transcription factor forkhead box protein 3 (FOXP3) directly bound to the promoter of LAPTM5 and negatively regulated its expression. Taken together, the present findings indicated that LAPTM5, negatively regulated by FOXP3, promoted the malignant phenotypes of breast cancer through activating the Wnt/ß­catenin signaling pathway.

SbNAC9 Improves Drought Tolerance by Enhancing Scavenging Ability of Reactive Oxygen Species and Activating Stress-Responsive Genes of Sorghum.

Drought stress severely threatens the yield of cereal crops. Therefore, understanding the molecular mechanism of drought stress response of plants is crucial for developing drought-tolerant cultivars. NAC transcription factors (TFs) play important roles in abiotic stress of plants, but the functions of NAC TFs in sorghum are largely unknown. Here, we characterized a sorghum NAC gene, SbNAC9, and found that SbNAC9 can be highly induced by polyethylene glycol (PEG)-simulated dehydration treatments. We therefore investigated the function of SbNAC9 in drought stress response. Sorghum seedlings overexpressing SbNAC9 showed enhanced drought-stress tolerance with higher chlorophyll content and photochemical efficiency of PSII, stronger root systems, and higher reactive oxygen species (ROS) scavenging capability than wild-type. In contrast, sorghum seedlings with silenced SbNAC9 by virus-induced gene silencing (VIGS) showed weakened drought stress tolerance. Furthermore, SbNAC9 can directly activate a putative peroxidase gene SbC5YQ75 and a putative ABA biosynthesis gene SbNCED3. Silencing SbC5YQ75 and SbNCED3 led to compromised drought tolerance and reduced ABA content of sorghum seedlings, respectively. Therefore, our findings revealed the important role of SbNAC9 in response to drought stress in sorghum and may shed light on genetic improvement of other crop species under drought-stress conditions.

The Effect of Business Operating Systems on Nursing Home Termination.

Objectives: Nursing home terminations have increased worldwide due to rising costs, staffing shortages, and the coronavirus disease pandemic. However, little is known about the impact that business operating systems have on nursing home termination. Methods: This study used the National Long-term Care database, which comprised 7,842 operating nursing homes in January 2018. Nursing home termination was identified when nursing homes discontinued provision of long-term care services to all residents between January 2018 and December 2020. Business operating systems that were reimbursed by the LTC insurance system were the exposure of interest. The logistic regression model for nursing home termination included a series of organizational, internal, and external factors as covariates. Results: From 2018 to 2020, 83 (1.1%) nursing homes were terminated. The proportion of reimbursed nursing homes varied greatly depending on the type of business operating systems. Implementing physical function training and improving working conditions were significantly associated with a lower risk of nursing home termination. Conclusion: Financial incentives to several business operating systems are an effective way to build a sustainable environment for nursing homes to continue to exist.

Effects of cost sharing on long-term care service utilization among home-dwelling older adults in Japan.

OBJECTIVES: This study aimed to examine the effect of increased cost sharing on long-term care (LTC) service utilization among home-dwelling older adults, using nationwide long-term care insurance (LTCI) claims data in Japan. METHODS: In August 2015, the coinsurance rate for Japanese LTCI increased from 10% to 20% for higher-income beneficiaries. We analyzed 27,911,076 person-month observations between April 2015 and July 2016 from 1,983,163 home-dwelling older adults (aged ≥ 65 years). We employed a difference-in-differences approach to estimate the effect of the increased coinsurance rate on overall LTC service utilization and for each of the four main service subcategories. The control group comprised those whose coinsurance rates remained at 10%. RESULTS: The treatment group, whose coinsurance rate increased, accounted for 9.6% of all participants. The raised coinsurance rate caused statistically significant reductions of 0.46% (95% confidence interval [CI]: 0.36%, 0.56%) and $25.7 (95% CI: $23.7, $27.8) in the percentage of utilization of LTC services and total monthly LTC expenditures per person, respectively. Service utilization decreased in each of the four service subcategories. CONCLUSIONS: The increased coinsurance rate resulted in statistically significant but small reductions in LTC service utilization overall and in each service type among higher-income home-dwelling beneficiaries. Requiring more cost sharing from higher-income individuals may alleviate the fiscal burden on LTC systems without serious reductions in service utilization.