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We demonstrate a hybrid solution for simultaneous transfer of ultra-stable optical frequency, RF frequency and time signal on a 100 km fiber spool with the same wavelength based on coherent demodulation and optical phase-lock-loop (OPLL). The one pulse per second (1PPS) is encoded by phase and RF frequency is encoded with an intensity modulator. The noise caused by fiber link is compensated by the round-trip method. And the bad effect on optical frequency caused by optical phase modulation (PM) can be cleaned using OPLL. When the fiber link is stabilized, the transferred time deviation (TDEV) can be 2.4E-11@1s and 1.9E-12@104s, RF frequency stability can achieve 8.0E-14@1s and 2.5E-17@104s, the modified Allan deviation (MDEV) of cleaned optical frequency can be 1.4E-16@1s and 1.6E-19@104s.

The tumorous niche may drive the plasticity of heterogeneity and cancer stemness, leading to drug resistance and metastasis, which is the main reason of treatment failure in most cancer patients. The aim of this study was to establish a tumor microenvironment (TME)-based screening to identify drugs that can specifically target cancer stem cells (CSCs) and cancer-associated fibroblasts (CAFs) in the TME. Methods: Lung cancer patient-derived cancer cell and CAFs were utilized to mimic the TME and reproduce the stemness properties of CSCs in vitro and develop a high-throughput drug screening platform with phenotypical parameters. Limiting dilution assay, sphere-forming and ALDH activity assay were utilized to measure the cancer stemness characteristics. In vivo patient-derived xenograft (PDX) models and single-cell RNA sequencing were used to evaluate the mechanisms of the compounds in CSCs and CAFs. Results: The TME-based drug screening platform could comprehensively evaluate the response of cancer cells, CSCs and CAFs to different treatments. Among the 1,524 compounds tested, several drugs were identified to have anti-CAFs, anticancer and anti-CSCs activities. Aloe-emodin and digoxin both show anticancer and anti-CSCs activity in vitro and in vivo, which was further confirmed in the lung cancer PDX model. The combination of digoxin and chemotherapy improved therapeutic efficacy. The single-cell transcriptomics analysis revealed that digoxin could suppress the CSCs subpopulation in CAFs-cocultured cancer cells and cytokine production in CAFs. Conclusions: The TME-based drug screening platform provides a tool to identify and repurpose compounds targeting cancer cells, CSCs and CAFs, which may accelerate drug development and therapeutic application for lung cancer patients.

Premature atrial complexes (PACs) have been suggested to increase the risk of adverse events. The distribution of PAC burden and its dose–response effects on all-cause mortality and cardiovascular death had not been elucidated clearly. We analyzed 15,893 patients in a medical referral center from July 1st, 2011, to December 31st, 2018. Multivariate regression driven by ln PAC (beats per 24 h plus 1) or quartiles of PAC burden were examined. Older group had higher PAC burden than younger group (p for trend p p = 0.001) or sub-distribution model (HR = 1.12, 95% CI = 1.04‒1.21, p = 0.004). In ordinal PAC model, 4th quartile group had significantly higher risk of all-cause mortality than those in 1st quartile group (HR = 1.47, 95% CI = 1.13‒1.94, p = 0.005), but no difference in cardiovascular death were found in competing risk analysis. In subgroup analysis, the risk of high PAC burden was consistently higher than in low-burden group across pre-specified subgroups. In conclusion, PAC burden has a dose response effect on all-cause mortality and cardiovascular death.

Conversion of inorganic-organic frameworks (ceramic precursors and ceramic-polymer mixtures) into solid mass ceramic structures based on photopolymerization process is currently receiving plentiful attention in the field of additive manufacturing (3D printing). Various techniques (e.g., stereolithography, digital light processing, and two-photon polymerization) that are compatible with this strategy have so far been widely investigated. This is due to their cost-viability, flexibility, and ability to design and manufacture complex geometric structures. Different platforms related to these techniques have been developed too, in order to meet up with modern technology demand. Most relevant to this review are the challenges faced by the researchers in using these 3D printing techniques for the fabrication of ceramic structures. These challenges often range from shape shrinkage, mass loss, poor densification, cracking, weak mechanical performance to undesirable surface roughness of the final ceramic structures. This is due to the brittle nature of ceramic materials. Based on the summary and discussion on the current progress of material-technique correlation available, here we show the significance of material composition and printing processes in addressing these challenges. The use of appropriate solid loading, solvent, and preceramic polymers in forming slurries is suggested as steps in the right direction. Techniques are indicated as another factor playing vital roles and their selection and development are suggested as plausible ways to remove these barriers.

Introduction: The effect of using closed suction drainage system with the proximal femoral nail antirotation (PFNA) system fixation on outcomes in treating intertrochanteric fractures (ITFs) is still unknown. This prospective randomized controlled trial aimed to examine whether routine drainage is useful for PFNA fixation in ITFs. Methods: A total of 80 patients with acute ITFs were treated with closed or mini-open reduction with PFNA fixation at the National Cheng Kung University Hospital and 60 eligible patients were randomized for whether to receive suction drainage. In clinical outcomes, the visual analog scale (VAS), morphine equivalent dosage, injured thigh width, body temperature, wound condition and wound infection were measured on postoperative day 1, 2, 4, 10, and 90. In laboratory outcomes, we evaluated hemoglobin and hematocrit levels postoperatively at different time points. Blood transfusion and total blood loss (TBL) were measured by Mercuriali's formula in millimeter. Results: The results revealed that the amount of blood transfusion received by the drained group (543.3 mL) was more than that by the undrained group (367.8 mL; p = 0.0074), and similarly, TBL in the drained group (750.1 mL) was more than that in the undrained group (537.4 mL; p = 0.0067). Regarding clinical and laboratory outcomes, compared with the undrained group, the drained group had a higher VAS score on postoperative day 2 (p = 0.0216). No difference was observed between the 2 groups for morphine equivalent dosage, thigh swelling, wound infection and hematoma, hospitalization period, or total number of complications at every time point after index procedure. Conclusions: Blood transfusion requirement and TBL were higher in the drained group than in the undrained group of PFNA fixation for ITFs. In addition, the closed drainage system may have manifested no short-term benefit for wound condition postoperatively.

Background Malignant pleural effusion (MPE)-macrophage (Mφ) of lung cancer patients within unique M1/M2 spectrum showed plasticity in M1–M2 transition. The M1/M2 features of MPE-Mφ and their significance to patient outcomes need to be clarified; furthermore, whether M1-repolarization could benefit treatment remains unclear. Methods Total 147 stage-IV lung adenocarcinoma patients undergoing MPE drainage were enrolled for profiling and validation of their M1/M2 spectrum. In addition, the MPE-Mφ signature on overall patient survival was analyzed. The impact of the M1-polarization strategy of patient-derived MPE-Mφ on anti-cancer activity was examined. Results We found that MPE-Mφ expressed both traditional M1 (HLA-DRA) and M2 (CD163) markers and showed a wide range of M1/M2 spectrum. Most of the MPE-Mφ displayed diverse PD-L1 expression patterns, while the low PD-L1 expression group was correlated with higher levels of IL-10. Among these markers, we identified a novel two-gene MPE-Mφ signature, IL-1β and TGF-β1, representing the M1/M2 tendency, which showed a strong predictive power in patient outcomes in our MPE-Mφ patient cohort (N = 60, p = 0.013) and The Cancer Genome Atlas Lung Adenocarcinoma dataset (N = 478, p Conclusions We identified MPE-Mφ on the M1/M2 spectrum and plasticity and described a two-gene M1/M2 signature that could predict the outcome of late-stage lung cancer patients. In addition, we found that “re-education” of these MPE-Mφ toward anti-cancer M1 macrophages using clinically applicable strategies may overcome tumor immune escape and benefit anti-cancer therapies.

Aggregation-induced emission luminogens (AIEgens) with a large electron donor and acceptor (D-A) conjugated system have been widely used in the development of organic light emitting diodes (OLEDs), chemosensors, and bioimaging materials due to their excellent properties such as high quantum yields, long emission wavelengths, controllable luminescence lifetimes, and nonlinear optics (NLO) properties. However, most of the AIE materials have been derived from limited classic AIE cores such as tetraphenylethene (TPE) and tetraphenylpyrazine (TPP), and thus, tedious syntheses or later modifications toward those AIEgens have always been unavoidable. In this report, a type of atypical AIEgens (designated as ASIQs) composed of large conjugated structures with a natural electron D-A system is disclosed, which shows large Stokes shifts, high photostabilities, excellent cell permeabilities, low biotoxicities, and good two-photon excited capacities, making them suitable for applications of one-photon/two-photon targeted imaging in live cells. In short, this work offers a type of atypical AIEgens which will possibly become an ideal platform leading to more structurally diverse and functionally excellent AIE-based luminescent materials.

A decline of T regulatory cell (Treg) number and function is associated with unexplained recurrent spontaneous abortion (URSA). However, the mechanism of downregulation of Tregs in URSA patients is still unknown. This study aimed to investigate the changes of Tregs in URSA patients and the epigenetic regulation for these changes. Venous blood samples were collected from 20 patients with URSA and 20 healthy control subjects. Treg number and inhibitory capacity, and Foxp3 mRNA expression and Foxp3 TSDR methylation were compared between the 2 groups. Correlations between Treg frequency and inhibitory function and TSDR methylation status were examined by Spearman's correlation. The proportion of Tregs within the population of CD4+ T cells and the expression of Foxp3 mRNA was significantly lower in URSA patients than in healthy control subjects. Tregs from URSA patients and healthy controls both significantly inhibited the cytotoxic activity of natural killer (NK) cells toward K562 targets; however, the inhibitory ability of Tregs from URSA patients was significantly lower than that from healthy controls. The methylation level of the Treg-specific demethylated region (TSDR) in the Foxp3 gene was significantly greater in URSA patients than in the controls, and the level of methylation was inversely correlated with the proportion of Tregs and Foxp3 mRNA expression in the peripheral blood. However, the methylation level was not correlated with the inhibitory function of Tregs. A decrease of Treg number and function may be related to the pathogenesis of URSA, and Foxp3 hypermethylation may be associated with the decreased Treg number.

Background To assess the associations of various HbA1c measures, including a single baseline HbA1c value, overall mean, yearly updated means, standard deviation (HbA1c-SD), coefficient of variation (HbA1c-CV), and HbA1c variability score (HVS), with microvascular disease (MVD) risk in patients with type 2 diabetes. Methods Linked data between National Cheng Kung University Hospital and Taiwan’s National Health Insurance Research Database were utilized to identify the study cohort. The primary outcome was the composite MVD events (retinopathy, nephropathy, or neuropathy) occurring during the study follow-up. Cox model analyses were performed to assess the associations between HbA1c measures and MVD risk, with adjustment for patients’ baseline HbA1c, demographics, comorbidities/complications, and treatments. Results In the models without adjustment for baseline HbA1c, all HbA1c variability and mean measures were significantly associated with MVD risk, except HVS. With adjustment for baseline HbA1c, HbA1c-CV had the strongest association with MVD risk. For every unit of increase in HbA1c-CV, the MVD risk significantly increased by 3.42- and 2.81-fold based on the models without and with adjustment for baseline HbA1c, respectively. The associations of HbA1c variability and mean measures with MVD risk in patients with baseline HbA1c Conclusions HbA1c variability, especially HbA1c-CV, can supplement conventional baseline HbA1c measure for explaining MVD risk. HbA1c variability may play a greater role in MVD outcomes among patients with relatively optimal baseline glycemic control compared to those with relatively poor baseline glycemic control.

Perovskite solar cell is a thin-film cell made from solution process including coating, sintering, crystallization, and then encapsulated to become a solar cell that can generate electricity at low cost. At present, the power conversion efficiency of laboratory-produced small cell (

OBJECTIVE Developing country-specific unit-cost catalogs is a key area for advancing economic research to improve medical and policy decisions. However, little is known about how health care costs vary by type 2 diabetes (T2D) complications across time in Asian countries. We sought to quantify the economic burden of various T2D complications in Taiwan. RESEARCH DESIGN AND METHODS A nationwide, population-based, longitudinal study was conducted to analyze 802,429 adults with newly diagnosed T2D identified during 1999–2010 and followed up until death or 31 December 2013. Annual health care costs associated with T2D complications were estimated, with multivariable generalized estimating equation models adjusted for individual characteristics. RESULTS The mean annual health care cost was $281 and $298 (2017 U.S. dollars) for a male and female, respectively, diagnosed with T2D at age CONCLUSIONS The cost estimates from this study are crucial for parameterizing diabetes economic simulation models to quantify the economic impact of clinical outcomes and determine cost-effective interventions.

Time-of-flight secondary-ion mass spectrometry (ToF-SIMS) has been used for gaining insights into perovskite solar cells (PSCs). However, the importance of selecting ion beam parameters to eliminate artifacts in the resulting depth profile is often overlooked. In this work, significant artifacts were identified with commonly applied sputter sources, i.e., an O

We assessed the effect of atosiban on pregnancy outcomes following in vitro fertilization (IVF) treatment among infertile women requiring different numbers of embryo transfer (ET) cycles (i.e., one, two, and more than two ET cycles). A longitudinal cohort study was conducted by utilizing the data from the Assisted Reproductive Technology Center in a university tertiary hospital during 2007-2017. Patients receiving IVF treatment with at least one ET cycle were included. Pregnancy outcomes following IVF treatment, including biochemical, clinical, and ongoing pregnancies, were investigated. The association between atosiban and IVF pregnancy was assessed using logistic generalized estimating equation models, with adjustment for time-varying clinical characteristics (e.g., maternal age) across multiple ET cycles for an individual. 403 women with 838 ET cycles were included, where 165 patients required one ET cycle, 133 patients required two ET cycles (a total of 266 ET cycles), and 105 patients required more than two ET cycles (a total of 407 ET cycles). Atosiban use was not significantly associated with pregnancy outcomes among all study infertile women undergoing IVF treatment. However, the results for women requiring more than two ET cycles showed significantly increased pregnancy rates associated with atosiban use (i.e., odds ratios [95% confidence interval] of 4.40 [1.52, 12.73] and 2.85 [1.45, 5.60] for clinical and ongoing pregnancies, respectively). This association was not observed for the women requiring only one or two ET cycles. Atosiban is a potential treatment for enhancing IVF pregnancy, especially among infertile women requiring more than two ET cycles.

Background: The efficacy, safety, and clinical outcomes for patients switch to generic rosuvastatin, compared with patients taking other brand-name atorvastatin, is unclear. Method: We retrospectively collected electronic medical records from January 1, 2013, to December 31, 2020, of patients who switched medication, because of hospital policy, from brand-name to generic rosuvastatin after March 14, 2018. we only considered patients who had taken the medication at least 1 year prior to and 1 year after that date. We also collected records of patients who consistently used brand-name atorvastatin during the same period. The efficacy of lipid control, potential adverse effects, clinical outcomes of major cardiovascular events (MACE), and medical expenses were compared between the 2 groups. Propensity score matching (PSM) was conducted to balance potential cofounders. Result: After 1:1 PSM, 592 patients were enrolled in the rosuvastatin and atorvastatin groups, and no significant difference was observed in their total cholesterol (TC) level difference (−4.38 ± 23.0 vs. −3.72 ± 26.95 mg/dL, P = 0.702), low-density lipoprotein (LDL-C) (−2.38 ± 19.89 vs. −2.42 ± 23.63 mg/dL, P = 0.976), or glycated hemoglobin (−0.05% ± 0.7% vs. −0.08% ± 0.76%, P = 0.543). No significant differences were noted in their cumulative MACE (2.70% vs. 3.89%, log-rank P = 0.265) after the switch date, and each person in the generic group had a 16% average reduction in their medical expenses. Conclusion: Switching to generic rosuvastatin led to comparable lipid-lowering efficacy, safety, and clinical outcomes and fewer medical expenses compared with consistently using brand-name atorvastatin.

ObjectiveThe present study aimed to evaluate the role of integrating the pretreatment neutrophil-to-lymphocyte ratio (NLR) into the eighth edition of the AJCC staging system for nasopharynx cancer in an endemic region.MethodsBetween May 2007 and December 2012, a total of 713 cases with NPC were retrospectively analyzed. The separation ability in terms of overall survival (OS), local failure-free survival (LFFS), distant metastasis-free survival (DMFS), and failure-free survival (FFS) was evaluated. The discriminatory ability was assessed using Harrell’s concordance index (c-index). Recursive partitioning analysis (RPA) was conducted and incorporated with pretreatment NLR.ResultsWhen integrated with NLR, the separate and discriminatory abilities for N classifications were improved in terms of OS and DMFS, but not for T categories. By using Recursive partitioning analysis, five subgroups were generated. Compared with the overall stage, the integration of NLR could not enhance the separate and discriminatory abilities. However, patients in the RPA 4 group gained significant benefits in terms of OS (HR 0.390 (95%CI 0.212-0.716), P = 0.002) and FFS (HR 0.548 (95%CI 0.314-0.958), P = 0.032) from the additional adjuvant chemotherapy after concurrent chemoradiotherapy.ConclusionThe integration of NLR into the 8th edition of the AJCC staging system could enhance the separation and discriminatory abilities for N classifications, but not for T categories. In addition, patients in the RPA 4 group could benefit from the addition of adjuvant chemotherapy to concurrent chemoradiotherapy.

Introduction: Infections are a leading cause of mortality in patients with systemic lupus erythematosus (SLE). Among various infections, invasive fungal infections (IFIs) have a particularly high mortality rate; however, studies examining IFIs in patients with SLE are limited. Methods: Patients diagnosed as having SLE between 1997 and 2012 were enrolled from Taiwan’s National Health Insurance Research Database along with age- and sex-matched non-SLE controls at a ratio of 1:10. IFIs were identified based on International Classification of Diseases, Ninth Revision, Clinical Modification codes and validated by the prescriptions of systemic antifungal agents. The incidence rate (IR), incidence rate ratio (IRR), and all-cause mortality rate of IFIs and its subtypes were analyzed. A Cox multivariate regression model with time-dependent covariates was applied to analyze independent risk factors for IFIs. Results: A total of 24,541 patients with SLE and 245,410 non-SLE controls were included. We observed 445 IFI episodes in the SLE cohort, with an all-cause mortality rate of 26.7%. Candida spp. (52.8%) was the most common pathogen, followed by Cryptococcus spp. (18.2%) and Aspergillus spp. (18.2%). The IR of IFIs in the SLE cohort was 20.83 per 10,000 person-years, with an IRR of 11.1 [95% confidence interval (CI): 9.8–12.6] relative to the non-SLE controls. Juvenile patients with SLE aged ⩽18 years had the highest IRR of 47.2 (95% CI: 26.9–86.8). Intravenous steroid therapy administered within 60 days (hazard ratio: 29.11, 95% CI: 23.30–36.37) was the most critical risk factor for overall IFIs and each of the three major fungal pathogens. Distinct risk factors were found among different IFI subtypes. Conclusion: Patients with SLE had a higher risk of IFIs, especially juvenile patients. Intravenous steroid therapy is the most critical risk factor for IFIs. This study provides crucial information for the risk stratification of IFIs in SLE. Plain Language Summaries Patients with systemic lupus erythematosus and physicians treating this patient group should be aware of the risk of invasive fungal infections. Invasive fungal infections (IFIs) are a severe complication with a high mortality rate among patients with systemic lupus erythematosus (SLE); however, studies on this topic are scant. We performed a nationwide population-based study in Taiwan to estimate the incidence and mortality of and risk factors for IFIs. We found an incidence rate of 20.83 per 10,000 person-years for IFIs, with a mortality rate of 26.7%. Juvenile patients aged ⩽18 years had the highest relative risk of IFIs. Although candidiasis was the most common IFI, cryptococcosis and aspergillosis should be concerned in juvenile patients as well. Intravenous steroid therapy was the most critical risk factor for all IFIs, and different immunosuppressive agents posed different risks in patients for acquiring certain fungal pathogens. Our findings provide pivotal epidemiological information and indicate risk factors for IFIs in patients with SLE. Age and exposure to specific immunosuppressants and steroids might help predict the risk of IFIs. Because the manifestation of these infections is sometimes indistinguishable from a lupus flare, physicians should be aware of this fatal complication, especially when patients are not responsive to immunosuppressive therapy. Early recognition, implication of diagnostic tools, and empirical antimicrobial agents can be the key to treating patients with IFIs. Additional studies are required to develop a risk management program for patients with SLE.

BackgroundThe use of atosiban during embryo transfer (ET), an oxytocin receptor antagonist, has been demonstrated to enhance pregnancy rate among infertile patients with endometriosis. However, its efficacy has not been assessed among those with concurrent adenomyosis, which may further affect pregnancy rate.MethodsThis retrospective cohort study assessed in vitro fertilization (IVF) pregnancy, and the effect of atosiban among 34 women with both endometriosis and adenomyosis (with 66 ET cycles), compared to 34 endometriosis patients without adenomyosis (with 54 ETs) and 38 patients with tubal factor (with 56 ETs). Multivariable logistic generalized estimating equation analyses were performed to assess pregnancy outcomes with adjustment for maternal and treatment characteristics.ResultsSignificantly higher chances of biochemical pregnancy and live birth among endometriosis patients without adenomyosis versus those with both endometriosis and adenomyosis were found (odds ratios [95% confidence intervals]: 2.981 [1.307, 6.803]; p=0.009, 2.694 [1.151, 6.304]; p=0.022). A significant positive association between atosiban use and biochemical pregnancy existed among endometriosis cases without adenomyosis (a 2.43-fold [1.01, 5.89] increase in successful pregnancy; p

In long-term clinical studies, recurrent event data are frequently collected to contrast the efficacy of two different treatments. However, the recurrent event process can be stopped by a terminal event, such as death. For analyzing recurrent event and terminal event data, joint frailty modeling has recently received considerable attention because it makes it possible to study the joint evolution over time of both recurrent and terminal event processes and gives consistent and efficient parameters. For a two-arm clinical trial design based on these data sets, there has been limited research on investigating the balanced design, let alone adaptive treatment allocation. Although equal sample size allocation obtained for both treatments is intuitively first adopted in a trial design, if one treatment is expected to be superior, it may be desirable to allocate more subjects to the effective treatment. In this article, we calculate the required sample size based on restricted randomization and then propose a target response-adaptive randomization procedure for recurrent and terminal event outcomes based on the joint frailty model. A randomization procedure, the doubly adaptive biased coin design that targets some optimal allocations, is implemented. The proposed adaptive treatment allocation schemes have been shown to be capable of reducing the number of trial participants who receive inferior treatment while simultaneously reaching an optimal target, as well as retaining a comparable test power as compared to a restricted randomization design. Finally, two clinical studies, the COAPT trial and the A-HeFT trial, are used to illustrate the advantages of adopting the proposed procedure.

The interaction between livelihood means and land use pattern of households is the core of the interactive coupling of the human-land system. This study focuses on Qinba mountainous area in southern Shaanxi province, a typical poverty-alleviated mountainous area. With the help of the coupling coordination degree model, kernel density estimation, and trend surface analysis, this study constructs the coupling coordination degree of livelihood efficiency and land use for households, and analyzes the differences between households’ livelihood efficiency and land use level, as well as the coupling coordination relationship between households livelihood efficiency and land use in different types and regions. The research conclusions are as follows. (1) For households in the Qinba mountainous area, southern Shaanxi province, the livelihood efficiency is at a medium level of 0.681, the land use is at a low level of 0.127, while the coupling coordination degree 0.526 is at the primary coordination state. (2) With the increase of nonagricultural degree, the coupling coordination degree of households increases first, and then decreases. (3) The coupling coordination degree for households east-to-west is “sagging”, while south-to-north diagram is “hogging”. (4) The distribution of the coupling coordination degree for agriculture-dependent households east-to-west (the “sagging” diagram) is opposite to the other types of households. By analogy, the distribution of the coupling coordination degree for nonagriculture and agriculture-dependent households north-to-south (the “hogging” diagram) is opposite to the other types of households. The coupling coordination between the households’ livelihood efficiency and land use level is affected by the households’ regional development level, natural resources, geographic location, infrastructure availability and many other factors. Making appropriate livelihood development plans based on the types of households and regional space can both effectively improve the livelihood conditions, as well as offer guidance in promoting regional human-land activity coordination and ensuring sustainable development.

Introduction Based on the immunosuppression of traditional antiangiogenic agents in the treatment of tumors and the newly proposed concept of antiangiogenic therapy combined with immunotherapy, this paper will mainly explore the prospects of PLXDC1 in stomach adenocarcinoma (STAD) regarding antiangiogenic therapy and immunotherapy.Methods First, the transcriptional and translational levels of PLXDC1 in STAD were analyzed using the Oncomine, The Cancer Genome Atlas (TCGA) and Human Protein Atlas databases and then univariate and multivariate Cox regression analyses were performed using TCGA data. Next, we explored the correlation between PLXDC1 and STAD immunity from multiple aspects. Finally, based on the acquisition of immunomodulators associated with PLXDC1 expression from TISIDB, we constructed PLXDC1-related immune prognostic signatures of four genes (NT5E, CTLA, TGFBR1, and CSF1R) and constructed a nomogram for predicting survival to analyze the clinical utility of PLXDC1 in immunotherapy.Results Our results demonstrated that PLXDC1 was highly expressed in STAD and that its high expression was associated with poor prognosis in STAD. Multivariate Cox analysis suggested that PLXDC1 could be used as an independent prognostic risk factor for STAD. The high-risk group for which we constructed PLXDC1-related immune prognostic signatures showed poorer prognosis compared to low-risk group, and the risk score of our model could be used as an independent risk factor for STAD prognosis. Moreover, the nomogram survival prediction system showed good accuracy of the constructed immune signatures.Conclusions In conclusion, PLXDC1 can serve as a biomarker for the diagnosis and treatment of STAD and it may also be a new target for STAD immunotherapy. Therefore, PLXDC1 can combine antiangiogenic therapy with immunotherapy.

An optimal therapeutic regimen for endometrial cancer with extra-uterine metastasis is unavailable. This study aims to improve our understanding of the genomic landscape of advanced endometrial cancer and identify potential therapeutic targets. The clinical and genomic profiles of 81 patients with stage III or IV endometrial cancer were integrated. To identify genomic aberrations associated with clinical outcomes, Cox proportional hazard regression was used. The impacts of the genomic aberrations were validated in vitro and in vivo. The mutation status of MET, U2AF1, BCL9, PPP2R1A, IDH2, CBL, BTK, and CHEK2 were positively correlated with poor clinical outcomes. MET mutations occurred in 30% of the patients who presented with poor overall survival (hazard ratio, 2.606, 95% confidence interval, 1.167~5.819, adjusted p-value, 0.067). Concurrent MET and KRAS mutations presented with the worst outcomes. MET mutations in hepatocyte growth factor (HGF)-binding (58.1%) or kinase (16.2%) domains resulted in differential HGF-induced c-MET phosphorylation. Different types of MET mutations differentially affected tumor growth and displayed different sensitivities to cisplatin and tyrosine kinase inhibitors. MET N375S mutation is a germline variant that causes chemoresistance to cisplatin, with a high incidence in Eastern Asia. This study highlights the ethnic differences in the biology of the disease, which can influence treatment recommendations and the genome-guided clinical trials of advanced endometrial cancer.

Background The impact of sagittal spinopelvic alignment on spondylolysis is well established in Caucasian populations. However, prior studies suggest that people from different ethnological backgrounds showed divergence, and a few studies that focused on Asian populations reported conflicting results. The aim of this study is to use the EOS imaging system to evaluate the spinopelvic parameters of spondylolysis patients, and their relationship with spondylolisthesis, disc degeneration, and age in a Taiwanese population. Methods Radiographic sagittal spinopelvic parameters for 45 spondylolysis patients and 32 healthy people were evaluated, including pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), thoracic kyphosis (TK), and lumbar lordosis (LL). The spinopelvic parameters were compared between spondylolytic and control groups. These parameters were further compared between spondylolytic subjects with and without spondylolisthesis, with and without high-grade disc degeneration, and young ( Results The PI and LL of the spondylolytic group (52.6°±12.0° and 41.3°±15.2°) were significantly higher than those of the healthy control group (47.16°±7.95° and 28.22°±10.65°). Further analysis of the spondylolytic patients revealed that those with high-grade disc degeneration were more prone to spondylolisthesis (92.3 %) compared to those without (50 %; p = 0.001). The middle-aged group had significantly higher rates of spondylolisthesis (80 %) and high-grade disc degeneration (52.4 %) compared with those for the young group (45 and 16.7 %, respectively; p = 0.017 and 0.047, respectively). No statistically significant difference in the sagittal spinopelvic parameters was found when spondylolytic patients were divided according to the occurrence of spondylolisthesis or high-grade disc degeneration. Conclusions In a Taiwanese population, PI and LL were significantly larger in spondylolytic patients. Disc degeneration and age were associated with the occurrence of spondylolisthesis. Ethnological differences should thus be taken into account when making clinical decisions regarding spondylolysis in a Taiwanese population.

Purpose: The objective of this study was to determine the independent risk factors associated with peripheral venous catheter (PVC) failure and develop a model that can predict PVC failure. Methods: This prospective, multicenter cohort study was carried out in nine tertiary hospitals in Suzhou, China between December 2017 and February 2018. Adult patients undergoing first-time insertion of a PVC were observed from catheter insertion to removal. Logistic regression was used to identify the independent risk factors predicting PVC failure. Results: This study included 5345 patients. The PVC failure rate was 54.05% ( n = 2889/5345), and the most common causes of PVC failure were phlebitis (16.3%) and infiltration/extravasation (13.8%). On multivariate analysis, age (45–59 years: OR, 1.295; 95% CI, 1.074–1.561; 60–74 years: OR, 1.375; 95% CI, 1.143–1.654; ⩾75 years: OR, 1.676; 95% CI, 1.355–2.073); department (surgery OR, 1.229; 95% CI, 1.062–1.423; emergency internal/surgical ward OR, 1.451; 95% CI, 1.082–1.945); history of venous puncture in the last week (OR, 1.298, 95% CI 1.130–1.491); insertion site, number of puncture attempts, irritant fluid infusion, daily infusion time, daily infusion volume, and type of sealing liquid were independent predictors of PVC failure. Receiver operating characteristic curve analysis indicated that a logistic regression model constructed using these variables had moderate accuracy for the prediction of PVC failure (area under the curve, 0.781). The Hosmer-Lemeshow goodness of fit test demonstrated that the model was correctly specified (χ2 = 2.514, p = 0.961). Conclusion: This study should raise awareness among healthcare providers of the risk factors for PVC failure. We recommend that healthcare providers use vascular access device selection tools to select a clinically appropriate device and for the timely detection of complications, and have a list of drugs classified as irritants or vesicants so they can monitor patients receiving fluid infusions containing these drugs more frequently.

A slouching posture during smartphone usage increases gravitational loadings on the cervical spine, which may lead to neck pain and degeneration. The objective of the present study was to investigate the head, neck and trunk angles in different smartphone-usage postures, as well as the posture-correction effects and comfort scores of three neck collars. This was a prospective cohort study in which 41 healthy young subjects aged 18–25 were recruited. The head, neck and trunk angles were measured in all participants during a neutral position and three smartphone-using postures, including sitting with and without back support and standing. The postural correction and comfort scores of three collars (Aspen Vista, Sport-aid and our customized 3D printed collars) were compared. Smartphone use increased the head and neck flexion angles in all postures, and sitting without back support showed the greatest head and neck flexion angles. The posture-correcting effect of the customized collar was better than the Aspen Vista and Sport-aid collars. In addition, the customized collar was more comfortable to wear than the other two collars in most contact areas. Smartphone use increased both the head and neck flexion in different postures, and the proposed customized 3D-printed cervical collar significantly reduced the head and neck angles. These slides can be retrieved under Electronic Supplementary Material.

Using a novel ultraviolet (UV) irradiation method, we processed a high-performance thin-film transistor (TFT) at low temperatures. Satisfactory device integrity that was demonstrated by high field-effect mobility values of 92 and 43 cm2/Vs, small subthreshold slopes of 74 and 81 mV/decade, and ON-current/ OFF-current values of $3\times 10^{6}$ and $7\times 10^{5}$ was achieved for the SnO2 TFT at low processing temperatures of 180 °C and 100 °C, respectively. The results of X-ray photoelectron spectroscopy showed that the UV irradiation considerably increased the presence of Sn4+ and reduced the presence of unwanted Sn2+, even at low processing temperatures, improving the quality of SnO2.

This paper proposes a configurable direct digital frequency synthesizer (DDFS) based on the lookup-table (LUT)- rotation architecture. To break through the limitation of the single mode, the proposed DDFS is the first attempt which supports four-mode switching on chip. Taking the advantages of small LUT size and pipelined rotation, the DDFS achieves both high-speed and high-resolution properties. The multi-bit rotation tree is helpful to reduce the latency and register usage, which improves the agility and energy efficiency of the DDFS. A partition problem is raised in this paper, and we estimate the optimal solution through both the theory and experiment. Based on the partition, an output can achieve the highest spurious-free dynamic range (SFDR) with as small as possible LUT size. The functionality of the proposed DDFS has been validated in a Xilinx ZedBoard field-programmable gate array. The synthesis and layout results show that the chip achieves maximum 102-dBc SFDR and 2.2-GHz clock frequency. The power consumption and latency cycles reach minimum 6.9 mW/GHz and 7 cycles, which are 20% and 30% reduction compared with the state-of-the-art DDFS.

Fang Su*, Kaihua Chen*, Zhongguo Liang, Song Qu, Ling Li, Long Chen, Yunli Yang, Chunhua Wu, Xia Liang, Xiaodong ZhuDepartment of Radiation Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of China*These authors contributed equally to this workObjective: Even in early-stage hepatocellular carcinoma (HCC), patients are often ineligible for surgical resection, transplantation, or local ablation due to advanced cirrhosis, donor shortage, or difficult tumor location. To compare the safety and efficacy of different fractions on the survival of patients with tumors smaller than 10 cm in size, hepatocellular carcinoma (HCC) patients ineligible for curative therapies were treated with three-dimensional conformal radiotherapy (3DCRT).Methods: A total of 198 HCC patients who had tumors smaller than 10 cm and were not eligible for surgical resection or local ablation therapy received 3DCRT. Participants were separated into two groups. The treatment for Group A (n=111) was a median total dose of 53Gy with a fraction of 2.5–4.9Gy given three times a week, while treatment for Group B (n=87) was a median total dose of 52Gy with a fraction of 5.0–7.0 Gy given three times a week. Propensity score matching (PSM) was conducted, and after the PSM, 81 pairs of patients arose. The Kaplan–Meier method was adopted to analyze overall survival; multivariate analysis was applied to identify the prognostic factors of survival.Results: The median follow-up time was 19.7months (ranging from 1 to 186months). The median survival for Group A patients versus Group B patients was 14.4 versus 24.8months (P=0.003), respectively. The overall survival rates at 1, 3, and 5years were 57.7%, 30.6%, and 18.9% for Group A patients and 73.6%, 43.7%, and 33.3% for Group B patients, respectively (P=0.009). In addition, the results in the PSM model appeared to be similar between the two groups. After PSM, the association between four independent prognostic factors and worse overall survival was discovered as follows: tumor size (>5 cm), Child–Pugh class B, portal vein tumor thrombosis, and fraction of 2.5−4.9Gy/fx. The two groups also shared similar toxicities.Conclusions: Higher fraction dose radiotherapy delivered by 3DCRT was effective, as it offered a survival benefit without aggravating the toxicities in patients with small- to medium-sized HCC tumors who were ineligible for curative therapies.Keywords: three-dimensional conformal radiotherapy, higher fraction dose, hepatocellular carcinoma, curative therapy, survival

Owing to its unique capability to sustain computation progress over power outages, a nonvolatile processor (NVP) is promising for energy-harvesting-powered Internet-of-Things devices. However, the widespread application of NVP is continually blocked by the system integration issues and the configuration overheads of peripheral devices. This paper presents a nonvolatile system-on-chip (NVSoC) with improved integration level, power management flexibility, and system wake-up speed. An on-chip power management subsystem is designed to minimize the number of external components while supporting versatile power policies. And a direct peripheral restore architecture is outlined, which enables a fast and parallel re-configuration of peripheral devices after the resumption of power supply. A test chip is fabricated in a 130-nm ferroelectric-CMOS process with 22.09-mm2 area. Measurement results show 6 $\times $ higher data throughput as compared with a conventional NVP when facing power failures.

Graphene is an ideal material for high-performance photodetectors because of its superior electronic and optical properties. However, graphene’s weak optical absorption limits the photoresponsivity of conventional photodetectors based on planar (two-dimensional or 2D) back-gated graphene field-effect transistors (GFETs). Here, we report a self-rolled-up method to turn 2D buried-gate GFETs into three-dimensional (3D) tubular GFETs. Because the optical field inside the tubular resonant microcavity is enhanced and the light–graphene interaction area is increased, the photoresponsivity of the resulting 3D GFETs is significantly improved. The 3D GFET photodetectors demonstrated room-temperature photodetection at ultraviolet, visible, mid-infrared, and terahertz (THz) regions, with both ultraviolet and visible photoresponsivities of more than 1 A W–1 and photoresponsivity of 0.232 A W–1 at 3.11 THz. The electrical bandwidth of these devices exceeds 1 MHz. This combination of high photoresponsivity, a broad spec...

The information that the brain perceives is usually consistent with a range of possible incentives. Therefore, all of our perceptual decisions are almost made in an uncertain situation. As we all know, this uncertainty affects our behavior, but how this uncertainty to modify human behavior is unclear. We attempt to establish the relationship between financial market behavior and external stimulus information. We adopt a new approach that is entirely different from the existing literature. This approach combines neuroscience and machine learning methods to explore how the brain perceives external stimulus information and ultimately influences financial market behavior. We improve the BP neural network in two aspects. Firstly, the output of the brain perception model serves as the input of the BP neural network. By this method, the number of input nodes of the BP neural network can be reduced to six, and the mental process behind the stimulus is simulated. Secondly, we optimize the parameters of the brain perception model and construct the optimal brain perception model for specific external stimuli. By comparing the performance of all models, the results show that the improved BP neural network is superior to other models. Firstly, in all two periods, trends are similar between the improved BP neural network and other models. Secondly, in all three samples, except for one result, the average prediction performance of the improved BP neural network is better than other models.

Three D–A π-conjugated copolymers PnTIF (where n = 2, 4, or 6), composed of isoindigo electron acceptor units and difluorinated bithiophene (BTF) electron donor units, were synthesized and characterized. The HOMO and LUMO energy levels, solubility (and miscibility with PCBM), crystallinity (and crystalline orientation) and PnTIF:PCBM thin film morphology (nano-fibrillar network and phase separation) of the copolymers could be adjusted by the number (0 for P2TIF, 1 for P4TIF, 2 for P6TIF) of flexible 3-dodecylthiophene spacers between the isoindigo and BTF units. From the tested polymer solar cells fabricated with PnTIF:PCBM bulk heterojunctions, P4TIF:PC61BM solar cells exhibited a remarkably high short-circuit current density of ∼22 mA cm−2 together with a fill factor of ∼61% and an open-circuit voltage >0.80 volt, resulting in a power conversion efficiency of 10.7%, making it one of the highest among PC61BM-based polymer solar cells.

Piezoelectric materials have gained a lot of attention in the last few decades as they introduce a renewable and sustainable approach for energy harvesting from vibrations or mechanical deformation in our environment. Among piezoelectric materials, polyvinylidene fluoride (PVDF) is one of the most commonly used piezoelectric polymers due to its high flexibility and piezoelectric performances. In this work, engineered cementitious composites (ECC) incorporating flexible PVDF based piezo polymer has been investigated as an innovative energy harvesting system to scavenge energy from mechanical deflection of ECC. Synchronous flexural test and voltage data recordings were employed to evaluate the voltage capture efficiency of two different lengths of PVDF (41 mm and 73 mm). The various loading rates of four-point bending tests were conducted to assess the energy harvesting performance. The results show that the voltage/power generated by the system is more efficient for longer PVDF samples as compared to the shorter ones when subjected to the four-point flexural test. High loading rates were found to be favorable for energy harvesting. The experimental results lay a solid foundation for potential energy harvesting application of the new cementitious composite system for development of multi-function building materials.

Graphene photodetectors have drawn a lot of interest due to their superior properties. For entering real applications, the existing open-face graphene photodetectors need to be properly protected to obtain long term stability. Here we demonstrate a facile method to obtain air-stable graphene photodetectors by directly depositing Si3N4 layer on the surface of buried-gate graphene field-effect transistors (GFETs). The electrical and photoelectrical properties of the Si3N4-encapsulated GFETs were carefully investigated and compared with that of the reference open-face GFETs. A photoresponsivity of 6.3 mA/W was obtained under a gate bias of 6 V, which was over 4 times higher than the photoresponsivities of typical back-gated GFET photodetectors under gate biases up to 80 V. Furthermore, the Si3N4-encapsulated GFET photodetectors demonstrated good stability for several months.

In order to efficiently and effectively convert the tire point cloud to the 3D CAD model, a feature-based reverse modeling method reflecting the design intent of pattern structure is proposed in this paper. The concrete research contents are as follows. Firstly, the 3D scan line point cloud is transformed into the 2D point cloud mapping matrix based on range image. Secondly, the segmentation of the tread point cloud is completed with tread data and groove data separated. Thirdly, the top surface, bottom surface, and pattern boundary information is extracted from the segmented mapping matrix. And then the clustering of transversal patterns is carried out by calculating the similarity in order to repair pattern boundary and reduce human interactions. Finally, on the basis of the extracted parameters of pattern design feature, a semantic feature modeling method orienting at 3D tread pattern model is constructed. On the basis of the above theoretical study, a feature-based reverse modeling system for tire structure design is developed on the CATIA V5 platform by CAA. Test examples show the practicality of the system in tire pattern reverse modeling.

The combination of the part features and attention mechanism has been made remarkable progress in Person Re-IDentification (REID), but part-based approaches are still ignoring the relations of inter-part and missing discriminative local feature representations. The Refined Spatial Interactions of Inter-part for Person Re-IDentification (RSIPR) is proposed to solve above problems. (RSIPR) consists of two main components: 1) Self Filter Attention (SFA) mechanism is employed to extract discriminatory representations from the pedestrian image adaptively. 2) Refined Spatial Interactions (RSI) is utilized to refine the interactions of inter-part and avoid ignoring the global perception due to the pedestrain is cropped into patches directly. Extensive experiments have been implemented to validate the superiority of the (RSIPR), and it has been demonstrated that the (RSIPR) achieves the state-of-the-art method without re-ranking [1] algorithm.

Circular economy is a critical approach to realize the coordinated development of society, economy, and ecological environment. Given the fact that urban is a complex system in which human beings integrate material, energy, information, and natural environment and interact and influence each other, reviewing the urban circular economy research and development could benefit for having a better and comprehensive understanding on urban complexity. Mainly based on the Chinese literature studies from 1999 to 2020, this study aims to present an in-depth analysis of the research themes, policy systems, and index system of Chinaʼs urban-scale circular economy, discuss the changes and evolution trends of themes, levels, and perspectives in time series, sort out the policy systems at both the national and local levels, and analyze the design principles and application fields of indicators. Finally, we propose that future development of an urban circular economy should be built based on modern techniques, technologies, and models. The construction of development mechanism on the circular economy should be framed as “government-led, market-driven, legal norms, policy support, technological support, and public participation” and inject concepts such as “Internet +,” “sharing economy,” “Internet of Things,” and “artificial intelligence.”

Background:6-Phosphofructo-2-kinase/fructose-2,6-biphosphate-4 (PFKFB4) is a key factor that plays an important role in tumorigenesis. However, its role in triple-negative breast cancer (TNBC) progression needs to be further validated.We investigated whether PFKFB4 is directly involved in the oncogenic signaling networks of TNBC.Methods: First, we assessed the expression level of PFKFB4 in tumor tissue specimens by immunohistochemistry and evaluated its prognostic value. Next, the effect of PFKFB4 on TNBC cell growth and associated mechanisms were investigated.Finally, the results were further verified in vivo. Results: We found that PFKFB4 overexpression was associated with an unfavorable prognosis in TNBC patients. PFKFB4 was overexpressed in TNBC cell lines in hypoxic environments, and its overexpression promoted tumor progression in vitro and in vivo. Further analyses demonstrated that the possible mechanism might be that PFKFB4 overexpression facilitates TNBC progression by enhancing the G1/S phase transition by increasing the proteinlevelof CDK6 and phosphorylation of Rb.Conclusions: These data suggest that PFKFB4 plays significant roles in the tumorigenesis and development of TNBC.Trial registration: Retrospectively registered.

Few clinical studies have previously discussed patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteriuria. This study aimed to assess the effect of antimicrobial therapy on the mortality of patients with CRKP bacteriuria. Hospitalized adults with CRKP bacteriuria were enrolled retrospectively from 16 hospitals in Taiwan during 2013 and 2014. Critically ill patients were defined as those with an Acute Physiology and Chronic Health Evaluation (APACHE) II score &ge, 20. Multivariate Cox regression analysis was used to determine independent risk factors for 14- and 28-day mortality. Of 107 patients with CRKP bacteriuria, the 14-day and 28-day mortality was 14.0% and 25.2%, respectively. Thirty-three patients received appropriate antimicrobial therapy. In the multivariate Cox regression analysis, the APACHE II score &ge, 20 was the only independent risk factor for 14-day mortality (hazard ratio [HR]: 6.15, p = 0.024). APACHE II score &ge, 20 (HR: 3.05, p = 0.018) and male sex (HR: 2.57, p = 0.037) were associated with 28-day mortality. Among critically ill patients with CRKP bacteriuria, appropriate antimicrobial therapy was not associated with 14-day or 28-day survival. In conclusion, in patients with CRKP bacteriuria, the use of appropriate antimicrobial therapy was not an independent factor associated with reduced mortality. Our findings may inform future antibiotic stewardship interventions for bacteriuria caused by multidrug resistant pathogens.

Background Evidence is limited on excess risks of cardiovascular diseases (CVDs) associated with ambient air pollution in diabetic populations. Survival analyses without considering the spatial structure and possible spatial correlations in health and environmental data may affect the precision of estimation of adverse environmental pollution effects. We assessed the association between air pollution and CVDs in type 2 diabetes through a Bayesian spatial survival approach. Methods Taiwan’s national-level health claims and air pollution databases were utilized. Fine individual-level latitude and longitude were used to determine pollution exposure. The exponential spatial correlation between air pollution and CVDs was analyzed in our Bayesian model compared to traditional Weibull and Cox models. Results There were 2072 diabetic patients included in analyses. PM2.5 and SO2 were significant CVD risk factors in our Bayesian model, but such associations were attenuated or underestimated in traditional models; adjusted hazard ratio (HR) and 95% credible interval (CrI) or confidence interval (CI) of CVDs for a 1 μg/m3 increase in the monthly PM2.5 concentration for our model, the Weibull and Cox models was 1.040 (1.004–1.073), 0.994 (0.984–1.004), and 0.994 (0.984–1.004), respectively. With a 1 ppb increase in the monthly SO2 concentration, adjusted HR (95% CrI or CI) was 1.886 (1.642–2.113), 1.092 (1.022–1.168), and 1.091 (1.021–1.166) for these models, respectively. Conclusions Against traditional non-spatial analyses, our Bayesian spatial survival model enhances the assessment precision for environmental research with spatial survival data to reveal significant adverse cardiovascular effects of air pollution among vulnerable diabetic patients. Graphical abstract

Optical multiplexing based on luminescent materials with tunable color/lifetime has potential applications in information storage and security. However, the available tunable luminescent materials reported so far still suffer from several drawbacks of low efficiency or poor stability, thus restraining their further applications. Herein, we demonstrate a strategy to develop efficient and stable lanthanide coordination polymers (LCPs) with tunable luminescence as a new option for optical multiplexing. Their multicolor emission from green to red and naked-eye-sensitive green emission with tunable lifetime (from ca. 300 to ca. 600 μs) can be controlled by host differential sensitization and energy transfer between lanthanide ions. The quantum efficiencies of developed samples range from around 20 % to 46 % and the luminescence intensity/lifetime appear quite stable in polar solvents up to ten weeks. Furthermore, with the aid of inkjet printing and concepts of luminescence lifetime imaging and time-gated imaging, we illustrate their promising applications of information storage and security in spatial and temporal domains.

Activation I/O traffic is a critical bottleneck of video neural network processor. Recent works adopted an inter-frame difference method to reduce activation size. However, current methods can't fully adapt to the various precision and sparsity in differential data. In this paper, we propose the multi-channel precision-sparsity-adapted codec, which will separate the differential activation and encode activation in multiple channels. We analyze the most adapted encoding of each channel, and select the optimal channel number with the best performance. A two-channel codec hardware has been implemented in the ASIC accelerator, which can encode/decode activations in parallel. Experiment results show that our coding achieves 2.2x-18.2x compression rate in three scenarios with no accuracy loss, and the hardware has 42x/174x improvement on speed and energy-efficiency compared with the software codec.

Background Sarcopenia is an ever-increasingly recognized entity in aging or chronically-ill individuals. A recent surge of researches came out on sarcopenia in rheumatoid arthritis (RA). However, the results varied widely. We tried to assess the prevalence of and associated factors with sarcopenia in patients with RA. Methods We searched the investigations dealing with the prevalence of and associated factors with sarcopenia in RA from PubMed, EMBASE, CENTRAL, EBSCOhost, Airiti Library, CEPS, CNKI and J-STAGE from the inception to January 11, 2020. Effects regarding prevalence and associated factors were extracted and evaluated by random-effects model. Sensitivity analysis was also performed. Results Seventeen studies containing 3,140 RA subjects were identified. After exclusion of outliers, the pooled prevalence of sarcopenia was 31%. Neither ongoing-study districts nor diagnostic modalities affected prevalence significantly. Any associated factors being mentioned in at least two publications were analyzed, yielding functional limitation (Steinbrocker stage III/IV), high CRP and RF seropositivity as the significant risk factors. Based on disease durations, we carried out meta-regression and found DAS28 and HAQ are predictive models. There was no alteration in the interpretation of results from sensitivity analysis after removal of any studies skewed in sampling distribution. Conclusions The prevalence of sarcopenia in patients with RA is high, compared to that in general counterparts. Disease duration rather than age, residing area or diagnostic modalities influences sarcopenia development; DAS28 and HAQ predict occurrence. High index of suspicion to facilitate early detection of sarcopenia in RA patients is important.

This study explored heterogeneous treatment effects (HTEs) of the real-world use of dipeptidyl peptidase-4 inhibitors (DPP-4is) vs. sulfonylureas (SUs) on cardiovascular diseases (CVDs) and mortality in patients with type 2 diabetes. Utilizing Taiwan's National Health Insurance Research Database, 19,853 propensity score-matched pairs of DPP-4i and SU stable users were identified. Classification and regression tree analyses and Cox models were applied to explore HTEs, according to various patient characteristics, on the composite CVDs, three-point major adverse cardiovascular event (MACE), and all-cause mortality. The absolute risk difference (ARD), hazard ratio (HR), and 95% confidence interval (CI) were estimated for comparing treatment effects. CVD history, ischemic stroke, or transient ischemic attack (IS/TIA) history, and age at treatment initiation were significant treatment effect modifiers. Patients with prior IS/TIA but without any other prior CVDs benefited most in reduced risks of composite CVDs from using DPP-4i vs. SU (ARD -4.31%, 95% CI -7.48% to -1.14%, HR 0.81, 95% CI 0.69 ~ 0.95), followed by those without prior IS/TIA and CVDs and initiated with DPP-4i at age

PURPOSE Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) show efficacy in treating patients with lung adenocarcinoma with EGFR-activating mutations. However, a significant subset of targeted patients fail to respond. Unlike acquired resistance (AR), intrinsic resistance (IR) remains poorly understood. We investigated whether epigenomic factors contribute to patient-to-patient heterogeneity in the EGFR-TKI response and aimed to characterize the IR subpopulation that obtains no benefit from EGFR-TKIs. PATIENTS AND METHODS We conducted genome-wide DNA methylation profiling of 79 tumors sampled from patients with advanced lung adenocarcinoma before they received EGFR-TKI treatment and analyzed the patient responses. Pyrosequencing was performed in a validation cohort of 163 patients with EGFR-activating mutations. RESULTS A DNA methylation landscape of 216 CpG sites with differential methylation was established to elucidate the association of DNA methylation with the characteristics and EGFR-TKI response status of the patients. Functional analysis of 37 transcription-repressive sites identified the enrichment of transcription factors, notably homeobox ( HOX) genes. DNA methylation of HOXB9 (cg13643585) in the enhancer region yielded 88% sensitivity for predicting drug response (odds ratio [OR], 6.64; 95% CI, 1.98 to 25.23; P = .0009). Pyrosequencing validated that HOXB9 gained methylation in patients with a poor EGFR-TKI response (OR, 3.06; 95% CI, 1.13 to 8.19; P = .019). CONCLUSION Our data suggest that homeobox DNA methylation could be a novel tumor cellular state that can aid the precise categorization of tumor heterogeneity in the study of IR to EGFR-TKIs. We identified, for the first time, an epigenomic factor that can potentially complement DNA mutation status in discriminating patients with lung adenocarcinoma who are less likely to benefit from EGFR-TKI treatment, thereby leading to improved patient management in precision medicine.

We assessed the quality of life (QoL) and pregnancy outcomes of in vitro fertilization (IVF) treatment among infertile women with endometriosis, as compared to infertile women without endometriosis. Eighty-one (81) endometriosis women (with 142 embryo transfer [ET] cycles) and 605 non-endometriosis women (with 1063 ET cycles) were included. QoL was measured by FertiQoL at the date before ET. Pregnancy outcomes included biochemical pregnancy, ongoing pregnancy and live birth. Generalized estimating equation analyses were performed to assess the association between QoL and IVF pregnancy. Endometriosis-affected women had significantly lower QoL, as indicated by mind/body, treatment environment and total treatment scores, and total scores of FertiQoL (p p Lower QoL among women with endometriosis versus non-endometriosis during IVF treatment highlights the importance of developing strategies to improve their QoL, which may enhance following pregnancy rates in this population.

Background: Psoriasis has a complex etiology related to inflammation and dysregulated immune system. MicroRNA (miR)-125a is a miRNA intimately related to inflammation and immunity; therefore, we presumed that it might play a role in the pathogenesis of psoriasis. This study aimed to investigate the correlation of miR-125a with disease severity and inflammation in psoriasis patients, and the effect of miR-125a on proliferation, apoptosis as well as its target signaling pathway in keratinocytes. Methods: Sixty psoriasis patients were consecutively recruited, then lesional and non-lesional skin tissue samples were collected. miR-125a in lesional and non-lesional skin tissues, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-17 mRNA expressions in lesional skin tissues were detected. Then, miR-125a overexpression, control overexpression, miR-125a knockdown and control knockdown plasmids were transfected into HaCaT cells. Subsequently, cell proliferation, apoptosis, IL-23R, JAK2, and STAT3 expressions were assessed. Results: miR-125a was reduced in lesional skin tissue compared with non-lesional skin tissue (p < 0.001), and it distinguished lesional skin tissue from non-lesional skin tissue with a high area under curve of 0.917 (95% CI 0.866–0.968). Negative association of miR-125a in lesional skin tissue with lesional body surface area (p = 0.037) and psoriasis area and severity index score (p < 0.001) was found. Additionally, miR-125a was negatively correlated with TNF-α (p = 0.001), IL-1β (p = 0.014), and IL-17 (p = 0.003) in lesional skin tissue. In cellular experiments, miR-125a overexpression inhibited proliferation and promoted apoptosis, while miR-125a knockdown enhanced proliferation and repressed apoptosis in HaCaT cells. Additionally, miR-125a negatively regulated the IL-23R/JAK2/STAT3 pathway in HaCaT cells. Conclusion: miR-125a could facilitate the disease monitoring and probably has the potential to be a therapeutic target in psoriasis.

Women with threatened preterm labor (TPTL) resting at home face several life challenges, but their psychological well-being has been ignored. This study aimed to explore the status and related factors of the psychological status of women with TPTL resting at home, and to compare the psychological status differences between TPTL and healthy pregnant women.A cross-sectional, multiple time-point study was conducted to repeatedly assess depression, perceived stress, and distress in 49 TPTL women and 62 healthy pregnant women during pregnancy in Taiwan. Mann-Whitney U tests were used to compare the psychological status differences between these women and the generalized estimating equation was used to identify the factors related to their psychological status.The TPTL women's perceived stress at 24-27 weeks (p=0.047) and 32-35 weeks (p=0.04) and distress at each time point was significantly greater than that of healthy pregnant women (p0.001). The common distress experienced by TPTL women was the inability to provide self-care and family care, the baby's health and safety, and to request leave from work for bed rest. Positive personalities, gestational age, preterm birth history, follow-up status and employment have been shown to be related to the psychological status of TPTL women.The major limitation of this study is the small sample size.This study contributed to a better understanding of the emotional burdens of women with TPTL resting at home. Such findings highlight the need for constructing effective interventions to alleviate the psychological burden of these women.

Serum microRNAs (miRNAs) have been reported as novel biomarkers for various diseases. But circulating biomarkers for predicting the radiosensitivity of nasopharyngeal carcinoma (NPC) have not been used in clinical practice. To screen out of differently expressed serum miRNAs from NPC patients with different radiosensitivity may be helpful for its individual therapy. NPC patients with different radiosensitivity were enrolled according to the inclusion and exclusion criteria. RNA was isolated from serum of these NPC patients before treatment. We investigated the differential miRNA expression profiles using microarray test (GSE139164), and the candidate miRNAs were validated by reverse transcription-quantitative real time polymerase chain reaction (RT-qPCR) experiments. Receiver operating characteristic (ROC) analysis has been applied to estimate the diagnostic value. In this study, 37 serum-specific miRNAs were screened out from 12 NPC patients with different radiosensitivity by microarray test. Furthermore, RT-qPCR analysis confirmed that hsa-miR-1281 and hsa-miR-6732-3p were significantly downregulated in the serum of radioresistant NPC patients (P