Lung cancer is the most commonly diagnosed cancer worldwide, and metastasis in lung cancer is the leading cause of cancer‐related deaths. Thus, understanding the mechanism of lung cancer metastasis ...will improve the diagnosis and treatment of lung cancer patients. Herein, we found that expression of cluster of differentiation 109 (CD109) was correlated with the invasive and metastatic capacities of lung adenocarcinoma cells. CD109 is upregulated in tumorous tissues, and CD109 overexpression was associated with tumor progression, distant metastasis, and a poor prognosis in patient with lung adenocarcinoma. Mechanistically, expression of CD109 regulates protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling via its association with the epidermal growth factor receptor (EGFR). Inhibition of CD109 decreases EGFR phosphorylation, diminishes EGF‐elicited activation of AKT/mTOR, and sensitizes tumor cells to an EGFR inhibitor. Taken together, our results show that CD109 is a potential diagnostic and therapeutic target in lung cancer patients.
CD109 promotes lung cancer metastasis through promoting EGFR‐AKT‐mTOR signaling and CD109 is an independent prognostic marker for lung adenocarcinoma.
Computing-in-memory (CIM) based on embedded nonvolatile memory is a promising candidate for energy-efficient multiply-and-accumulate (MAC) operations in artificial intelligence (AI) edge devices. ...However, circuit design for NVM-based CIM (nvCIM) imposes a number of challenges, including an arealatency-energy tradeoff for multibit MAC operations, patterndependent degradation in signal margin, and small read margin. To overcome these challenges, this article proposes the following: 1) a serial-input non-weighted product (SINWP) structure; 2) a down-scaling weighted current translator (DSWCT) and positive-negative current-subtractor (PN-ISUB); 3) a currentaware bitline clamper (CABLC) scheme; and 4) a triple-margin small-offset current-mode sense amplifier (TMCSA). A 55-nm 1-Mb ReRAM-CIM macro was fabricated to demonstrate the MAC operation of 2-b-input, 3-b-weight with 4-b-out. This nvCIM macro achieved T MAC = 14.6 ns at 4-b-out with peak energy efficiency of 53.17 TOPS/W.
Genome-wide association studies (GWASs) have linked RRBP1 (ribosomal-binding protein 1) genetic variants to atherosclerotic cardiovascular diseases and serum lipoprotein levels. However, how RRBP1 ...regulates blood pressure is unknown.
To identify genetic variants associated with blood pressure, we performed a genome-wide linkage analysis with regional fine mapping in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) cohort. We further investigated the role of the RRBP1 gene using a transgenic mouse model and a human cell model.
In the SAPPHIRe cohort, we discovered that genetic variants of the RRBP1 gene were associated with blood pressure variation, which was confirmed by other GWASs for blood pressure. Rrbp1- knockout (KO) mice had lower blood pressure and were more likely to die suddenly from severe hyperkalemia caused by phenotypically hyporeninemic hypoaldosteronism than wild-type controls. The survival of Rrbp1-KO mice significantly decreased under high potassium intake due to lethal hyperkalemia-induced arrhythmia and persistent hypoaldosteronism, which could be rescued by fludrocortisone. An immunohistochemical study revealed renin accumulation in the juxtaglomerular cells of Rrbp1-KO mice. In the RRBP1-knockdown Calu-6 cells, a human renin-producing cell line, transmission electron and confocal microscopy revealed that renin was primarily retained in the endoplasmic reticulum and was unable to efficiently target the Golgi apparatus for secretion.
RRBP1 deficiency in mice caused hyporeninemic hypoaldosteronism, resulting in lower blood pressure, severe hyperkalemia, and sudden cardiac death. In juxtaglomerular cells, deficiency of RRBP1 reduced renin intracellular trafficking from ER to Golgi apparatus. RRBP1 is a brand-new regulator of blood pressure and potassium homeostasis discovered in this study.
Background
To compare the risks of major osteoporotic, vertebral, and non‐vertebral fractures between patients who discontinued anti‐osteoporosis medications.
Methods
We conducted a comparative ...effectiveness study with a nationwide population‐based cohort study design. Patients aged ≥50 years admitted between 2012 and 2015 for incident hip fractures and receiving denosumab or bisphosphonates with sufficient compliance for at least 1 year were included. Patients were categorized into persistent or non‐persistent denosumab or bisphosphonates users based on their subsequent use pattern. The main outcomes were subsequent hospitalizations for a major osteoporotic, vertebral or non‐vertebral fracture. Multivariate, time‐varying Cox proportional hazards model was used to evaluate the risk of major outcomes.
Results
Compared with persistent denosumab users, non‐persistent denosumab users had a significantly higher risk of major osteoporotic fractures (hazard ratio HR = 1.60; 95% confidence interval CI, 1.20–2.14), vertebral fractures (HR = 2.18; 95% CI, 1.46–3.24) and death (HR = 3.57; 95%CI, 2.63–4.84). However, the increased risk of fracture was not found in both persistent and non‐persistent bisphosphonates users. Noteworthy, the increased risk of vertebral fractures in non‐persistent denosumab users was more pronounced within 1 year post‐discontinuation (HR = 2.90; 95% CI, 1.77–4.74) and among patients who discontinued from 2‐year denosumab therapy (HR = 3.58; 95% CI, 1.74–7.40).
Discussion
Discontinuation of denosumab resulted in an increased risk of major osteoporotic fractures, especially vertebral fractures. The increased risk tends to reveal within 1 year post‐discontinuation and be greater after a longer treatment duration. Notably, only fracture with hospitalization was identified as our research outcome, the real risk of osteoporotic fracture post discontinuation is believed to be higher, especially for vertebral fracture.
Background and objective
The epidemiology of pediatric acquired demyelinating disorders remains to be clarified in many parts of Asia. We carry out this study to depict the epidemiology of pediatric ...multiple sclerosis (MS), neuromyelitis optica (NMO), and optic neuritis (ON) in Taiwan.
Methods
We conducted a retrospective nationwide population-based study using data from Taiwan’s National Health Insurance Research Database. Prevalent cases of pediatric MS and NMO during 2001–2015, and incident cases of pediatric MS, NMO, and ON during 2003–2015 were identified. The demographic features and comorbidities were investigated.
Results
We identified 403 MS, 42 NMO, and 1496 ON incident cases under the age of 20 during 2003–2015. The majority of pediatric MS (86.1%) and NMO (90.5%) patients were 10 years old or above. The incidence of MS and ON was relatively steady, while that of NMO increased prominently later during the study period. The average incidence of pediatric MS and NMO during 2011–2015 was 0.52 and 0.11 per 100,000 person-years, respectively. The female preponderance was evident for pediatric MS and NMO, and less so for pediatric ON. The most common autoimmune comorbidities for pediatric MS were thyrotoxicosis (1.0%) and systemic lupus erythematosus (0.7%).
Conclusion
The epidemiology of pediatric MS was largely stationary in Taiwan during 2001–2015, while the prevalence of pediatric NMO rose steeply during this period, probably reflecting better recognition of this clinical entity. Autoimmune comorbidities were uncommon for pediatric MS and NMO in Taiwan.
Overweight and obesity are important risk factors of gestational diabetes mellitus (GDM). Clustering of metabolic risk factors in early pregnancy may be a potential pathogenesis between the link of ...overweight/obesity and GDM. Since it remains unexplored, we investigated if overweight and obesity are associated with clustering of metabolic risk factors in early pregnancy and the risk of GDM in this cohort study.
Total 527 women who visited National Taiwan University Hospital for prenatal care in between November 2013 to April 2018 were enrolled. Risk factors of GDM in the first prenatal visit (FPV) were recorded. Overweight/obesity was defined if body mass index ≥24 kg/m2. GDM was diagnosed from the result of a 75g oral glucose tolerance test in 24-28 gestational weeks.
Overweight/obesity was associated with clustering of metabolic risk factors of GDM, including high fasting plasma glucose, high HbA1c, insulin resistance, high plasma triglyceride and elevated blood pressure in FPV (p<0.05). There was a positive relationship between the number of metabolic risk factors and the incidence of GDM (p <0.05). The odds ratios of HbA1c and diastolic blood pressure were higher in overweight/obese women, compared with those in normal-weight women.
Overweight/obesity is associated with clustering of metabolic risk factors in early pregnancy, which is correlated with higher risk of GDM. Our findings suggest that metabolic risk factors during early pregnancy should be evaluated in overweight/obese women.
Mesenchymal stem cells (MSCs) are promising tools for the treatment of diseases such as infarcted myocardia and strokes because of their ability to promote endogenous angiogenesis and neurogenesis ...via a variety of secreted factors. MSCs found in the Wharton's jelly of the human umbilical cord are easily obtained and are capable of transplantation without rejection. We isolated MSCs from Wharton's jelly and bone marrow (WJ-MSCs and BM-MSCs, respectively) and compared their secretomes. It was found that WJ-MSCs expressed more genes, especially secreted factors, involved in angiogenesis and neurogenesis. Functional validation showed that WJ-MSCs induced better neural differentiation and neural cell migration via a paracrine mechanism. Moreover, WJ-MSCs afforded better neuroprotection efficacy because they preferentially enhanced neuronal growth and reduced cell apoptotic death of primary cortical cells in an oxygen-glucose deprivation (OGD) culture model that mimics the acute ischemic stroke situation in humans. In terms of angiogenesis, WJ-MSCs induced better microvasculature formation and cell migration on co-cultured endothelial cells. Our results suggest that WJ-MSC, because of a unique secretome, is a better MSC source to promote in vivo neurorestoration and endothelium repair. This study provides a basis for the development of cell-based therapy and carrying out of follow-up mechanistic studies related to MSC biology.
Epithelial-mesenchymal transition (EMT)/mesenchymal-epithelial transition (MET) processes are proposed to be a driving force of cancer metastasis. By studying metastasis in bone marrow-derived ...mesenchymal stem cell (BM-MSC)-driven lung cancer models, microarray time-series data analysis by systems biology approaches revealed BM-MSC-induced signaling triggers early dissemination of CD133
/CD83
cancer stem cells (CSCs) from primary sites shortly after STAT3 activation but promotes proliferation towards secondary sites. The switch from migration to proliferation was regulated by BM-MSC-secreted LIF and activated LIFR/p-ERK/pS727-STAT3 signaling to promote early disseminated cancer cells MET and premetastatic niche formation. Then, tumor-tropic BM-MSCs circulated to primary sites and triggered CD151
/CD38
cells acquiring EMT-associated CSC properties through IL6R/pY705-STAT3 signaling to promote tumor initiation and were also attracted by and migrated towards the premetastatic niche. In summary, STAT3 phosphorylation at tyrosine 705 and serine 727 differentially regulates the EMT-MET switch within the distinct molecular subtypes of CSCs to complete the metastatic process.
To identify the prevalence of mental health problems and sleep disturbances among nursing students during the COVID-19 pandemic.
As a future professional workforce, nursing students are expected to ...play a role in controlling the COVID-19 pandemic; however, physical and mental health problems may hinder their willingness to stay in the nursing profession. Evidence of the prevalence of the health problems among nursing students related to COVID-19 may allow educators to manage their students’ health problems and make them feel more positive about their future careers.
Systematic review and meta-analysis. This study was prospectively registered with PROSPERO.
Databases, including CINAHL, Embase, PubMed and Web of Science, were searched for all related journal articles, from database inception to June 29, 2021, published between 2020 and 2021.
This review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using a PICOS search strategy. A DerSimonian–Laird random-effects model was used to estimate the prevalence and potential heterogeneity among the selected studies using the Cochran Q statistic and I-square test. Publication bias was assessed using the Egger intercept test.
Seventeen studies were included in the meta-analysis, representing 13,247 nursing students. During the COVID-19 pandemic, the prevalence of four health problems and sleep disturbances were identified. The health problem with the highest prevalence in nursing students was depression (52%). Other COVID-19-related health problems were fear (41%), anxiety (32%) and stress (30%) and sleep disturbances (27%).
The findings from this study showed that strategies are necessary to manage nursing students’ teaching and learning during the COVID-19 pandemic or similar future situations. Our results suggest that preparing modified distance learning might reduce the prevalence of health problems related to the educational process. In addition, providing regular mental health assessments or online mental health services to students may improve their mental health and increase their well-being. Nursing education policies regarding clinical practice remain to be formulated to ensure the achievement of competencies to support future careers while considering the mental readiness and safety of students.
One of the most puzzling problems of high temperature cuprate superconductor is the pseudogap phase (PG) at temperatures above the superconducting transition temperature in the underdoped regime. The ...PG phase is found by the angle-resolved photoemission spectra (ARPES) to have a gap at some regions in momentum space and a fraction of Fermi surface remained, known as Fermi arcs. The arc turns into a d-wave SC gap with a node below the SC transition temperature. Here, by studying a strongly correlated model at low temperatures, we obtained a phase characterized by two kinds of pairing order parameters with the total momentum of the Cooper pair to be zero and finite. The finite momentum pairing is accompanied with a spatial modulation of pairing order, i.e. a pair density wave (PDW). These PDW phases are intertwined with modulations of charge density and intra-unit cell form factors. The coexistence of the two different pairing orders provides the unique two-gaps like spectra observed by ARPES for superconducting cuprates. As temperature raises, the zero-momentum pairing order vanishes while the finite momentum pairing orders are kept, thus Fermi arcs are realized. The calculated quasiparticle spectra have the similar doping and temperature dependence as reported by ARPES and scanning tunneling spectroscopy (STS). The consequence of breaking symmetry between x and y due to the unidirectional PDW and the possibility to probe such a PDW state in the PG phase is discussed.
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