Assessing COVID-19 pandemic policies and behaviours and their economic and educational trade-offs across US states from Jan 1, 2020, to July 31, 2022: an observational analysis.

BACKGROUND: The USA struggled in responding to the COVID-19 pandemic, but not all states struggled equally. Identifying the factors associated with cross-state variation in infection and mortality rates could help to improve responses to this and future pandemics. We sought to answer five key policy-relevant questions regarding the following: 1) what roles social, economic, and racial inequities had in interstate variation in COVID-19 outcomes; 2) whether states with greater health-care and public health capacity had better outcomes; 3) how politics influenced the results; 4) whether states that imposed more policy mandates and sustained them longer had better outcomes; and 5) whether there were trade-offs between a state having fewer cumulative SARS-CoV-2 infections and total COVID-19 deaths and its economic and educational outcomes. METHODS: Data disaggregated by US state were extracted from public databases, including COVID-19 infection and mortality estimates from the Institute for Health Metrics and Evaluation's (IHME) COVID-19 database; Bureau of Economic Analysis data on state gross domestic product (GDP); Federal Reserve economic data on employment rates; National Center for Education Statistics data on student standardised test scores; and US Census Bureau data on race and ethnicity by state. We standardised infection rates for population density and death rates for age and the prevalence of major comorbidities to facilitate comparison of states' successes in mitigating the effects of COVID-19. We regressed these health outcomes on prepandemic state characteristics (such as educational attainment and health spending per capita), policies adopted by states during the pandemic (such as mask mandates and business closures), and population-level behavioural responses (such as vaccine coverage and mobility). We explored potential mechanisms connecting state-level factors to individual-level behaviours using linear regression. We quantified reductions in state GDP, employment, and student test scores during the pandemic to identify policy and behavioural responses associated with these outcomes and to assess trade-offs between these outcomes and COVID-19 outcomes. Significance was defined as p<0·05. FINDINGS: Standardised cumulative COVID-19 death rates for the period from Jan 1, 2020, to July 31, 2022 varied across the USA (national rate 372 deaths per 100 000 population [95% uncertainty interval [UI] 364-379]), with the lowest standardised rates in Hawaii (147 deaths per 100 000 [127-196]) and New Hampshire (215 per 100 000 [183-271]) and the highest in Arizona (581 per 100 000 [509-672]) and Washington, DC (526 per 100 000 [425-631]). A lower poverty rate, higher mean number of years of education, and a greater proportion of people expressing interpersonal trust were statistically associated with lower infection and death rates, and states where larger percentages of the population identify as Black (non-Hispanic) or Hispanic were associated with higher cumulative death rates. Access to quality health care (measured by the IHME's Healthcare Access and Quality Index) was associated with fewer total COVID-19 deaths and SARS-CoV-2 infections, but higher public health spending and more public health personnel per capita were not, at the state level. The political affiliation of the state governor was not associated with lower SARS-CoV-2 infection or COVID-19 death rates, but worse COVID-19 outcomes were associated with the proportion of a state's voters who voted for the 2020 Republican presidential candidate. State governments' uses of protective mandates were associated with lower infection rates, as were mask use, lower mobility, and higher vaccination rate, while vaccination rates were associated with lower death rates. State GDP and student reading test scores were not associated with state COVD-19 policy responses, infection rates, or death rates. Employment, however, had a statistically significant relationship with restaurant closures and greater infections and deaths: on average, 1574 (95% UI 884-7107) additional infections per 10 000 population were associated in states with a one percentage point increase in employment rate. Several policy mandates and protective behaviours were associated with lower fourth-grade mathematics test scores, but our study results did not find a link to state-level estimates of school closures. INTERPRETATION: COVID-19 magnified the polarisation and persistent social, economic, and racial inequities that already existed across US society, but the next pandemic threat need not do the same. US states that mitigated those structural inequalities, deployed science-based interventions such as vaccination and targeted vaccine mandates, and promoted their adoption across society were able to match the best-performing nations in minimising COVID-19 death rates. These findings could contribute to the design and targeting of clinical and policy interventions to facilitate better health outcomes in future crises. FUNDING: Bill & Melinda Gates Foundation, J Stanton, T Gillespie, J and E Nordstrom, and Bloomberg Philanthropies.

Targeting aberrant glycosylation to modulate microglial response and improve cognition in models of Alzheimer's disease.

Altered glycosylation profiles have been correlated with potential drug targets in various diseases, including Alzheimer's disease (AD). In this area, the linkage between bisecting N-acetylglucosamine (GlcNAc), a product of N-acetylglucosaminyltransferase III (GnT-III), and AD has been recognized, however, our understanding of the cause and the causative role of this aberrant glycosylation in AD are far from completion. Moreover, the effects and mechanisms of glycosylation-targeting interventions on memory and cognition, and novel targeting strategies are worth further study. Here, we showed the characteristic amyloid pathology-induced and age-related changes of GnT-III, and identified transcription factor 7-like 2 as the key transcription factor responsible for the abnormal expression of GnT-III in AD. Upregulation of GnT-III aggravated cognitive dysfunction and Alzheimer-like pathologies. In contrast, loss of GnT-III could improve cognition and alleviate pathologies. Furthermore, we found that an increase in bisecting GlcNAc modified ICAM-1 resulted in impairment of microglial responses, and genetic inactivation of GnT-III protected against AD mechanistically by blocking the aberrant glycosylation of ICAM-1 and subsequently modulating microglial responses, including microglial motility, phagocytosis ability, homeostatic/reactive state and neuroinflammation. Moreover, by target-based screening of GnT-III inhibitors from FDA-approved drug library, we identified two compounds, regorafenib and dihydroergocristine mesylate, showing pharmacological potential leading to modulation of aberrant glycosylation and microglial responses, and rescue of memory and cognition deficits.

Association Between Early Sexual Debut and New HIV Infections Among Adolescents and Young Adults in 11 African Countries.

We investigated the association between early sexual debut and HIV infection among adolescents and young adults. Analyzing data from nationally representative Population-Based HIV Impact Assessment (PHIA) surveys in 11 African countries, the research employed a multivariate logistic regression model to assess the relationship between the early sexual debut and new HIV infections in the age group of 10-24 years. The results revealed a significant and robust association, indicating that young individuals who experienced early sexual debut were approximately 2.65 times more likely to contract HIV than those who did not, even after accounting for other variables. These findings align with prior research suggesting that early initiation of sexual activity may increase vulnerability to HIV infection due to factors such as biological susceptibility and risky behaviors like low condom use and multiple sexual partners. The implications of these findings for HIV prevention strategies are substantial, suggesting that interventions aimed at delaying sexual debut could be an effective component in reducing HIV risk for this population. Targeted sex education programs that address the risks of early sexual debut may play a pivotal role in these prevention efforts. By employing a comprehensive approach, there is a possibility to advance efforts towards ending AIDS by 2030.

Ventriculoperitoneal shunting obstruction: a multicentre clinical audit for cerebrospinal fluid parameters and its prediction role.

BACKGROUND: Shunt obstruction is a type of ventriculoperitoneal shunt (VPS) failure. Whether changes in cerebrospinal fluid (CSF) parameters can influence shunt outcomes or not is debatable. METHODS: In this study, we retrospectively included adult hydrocephalus patients who received VPS from 6 general hospitals in different provinces of China from November 2013 to September 2021. The inclusion criteria: Patients with hydrocephalus of all etiologies underwent shunt surgery from 6 general hospitals in different provinces of China were included in the study. The exclusion criteria: 1.Patients under the age of 18; 2.Patients who had previous shunt surgery; 3. Shunt failure from other factors; 4.Patients died from other causes; 5. Patients with incomplete data. The CSF of shunt patients had been analyzed at the time of shunt insertion. The CSF samples were collected and analyzed when the shunt was implanted. The relationship between CSF parameters and the incidence rate of shunt obstruction in one year was analyzed. RESULTS: A total of 717 eligible patients from 6 hospitals were included, of whom 59(8.23%) experienced obstruction. Multivariate logistic regression analysis identified that protein level(odds ratio [OR] 1.161, 95% CI 1.005 ~ 1.341, p = 0.043), decreased glucose level(< 2.5 mmol/L)(odds ratio 3.784, 95% confidence interval 1.872 ~ 7.652, p = 0.001) and protein level increase(> 0.45 g/L) (odds ratio 3.653, 95% confidence interval 1.931 ~ 6.910, p = 0.001)were independent risk factors of shunt obstruction. CONCLUSION: This study suggested that increased protein level (> 0.45 g/L) and decreased glucose level (< 2.5 mmol/L) in CSF indicated an increased risk of shunt obstruction in a patient with hydrocephalus. Thus, shunt surgery should be more carefully considered when the CSF glucose and protein were abnormal.

Genome-Wide Identification of the Sulfate Transporters Gene Family in Blueberry (Vaccinium spp.) and Its Response to Ericoid Mycorrhizal Fungi.

Sulfur metabolism plays a major role in plant growth and development, environmental adaptation, and material synthesis, and the sulfate transporters are the beginning of sulfur metabolism. We identified 37 potential VcSULTR genes in the blueberry genome, encoding peptides with 534 to 766 amino acids. The genes were grouped into four subfamilies in an evolutionary analysis. The 37 putative VcSULTR proteins ranged in size from 60.03 to 83.87 kDa. These proteins were predicted to be hydrophobic and mostly localize to the plasma membrane. The VcSULTR genes were distributed on 30 chromosomes; VcSULTR3;5b and VcSULTR3;5c were the only tandemly repeated genes. The VcSULTR promoters contained cis-acting elements related to the fungal symbiosis and stress responses. The transcript levels of the VcSULTRs differed among blueberry organs and changed in response to ericoid mycorrhizal fungi and sulfate treatments. A subcellular localization analysis showed that VcSULTR2;1c localized to, and functioned in, the plasma membrane and chloroplast. The virus-induced gene knock-down of VcSULTR2;1c resulted in a significantly decreased endogenous sulfate content, and an up-regulation of genes encoding key enzymes in sulfur metabolism (VcATPS2 and VcSiR1). These findings enhance our understanding of mycorrhizal-fungi-mediated sulfate transport in blueberry, and lay the foundation for further research on blueberry-mycorrhizal symbiosis.

[Transcriptional regulation mechanism of differential accumulation of flavonoids in different varieties of Lonicera macranthoides based on metabonomics and transcriptomics].

This study aims to explore the molecular regulatory mechanism of the differential accumulation of flavonoids between 'Xianglei' and the wild type of Lonicera macranthoides. The flowers, stems, and leaves of the two varieties of L. macranthoides were collected. Ultra-performance liquid chromatography-mass spectrometry(UPLC-MS) and high-throughput sequencing(RNA-seq) were employed to screen out the differential flavonoids, key differentially expressed genes(DEGs) and transcription factors(TFs). Fourteen DEGs were randomly selected for verification by qRT-PCR. The results showed that a total of 17 differential flavonoids were obtained, including naringin chalcone, apigenin, and quercetin. The transcriptomic analysis predicted 19 DEGs associated with flavonoids, including 2 genes encoding chitin synthase(CHS) and 3 genes encoding chalcone isomerase(CHI). The regulatory network analysis and weighted gene co-expression network analysis(WGCNA) screen out the key enzyme genes CHS1, FLS1, and HCT regulating the accumulation of flavonoids. MYB12 and LBD4 may be involved in the biosynthesis of flavonoids by regulating the expression of key enzyme genes CHS1, FLS1, and HCT. The qRT-PCR and RNA-seq results were similar regarding the expression patterns of the 14 randomly selected DEGs. This study preliminarily analyzed the transcriptional regulatory mechanism for the differential accumulation of flavonoids in the two varieties of L. macranthoides and laid a foundation for further elucidating the regulatory effects of key enzyme genes and TFs on the accumulation of flavonoids.

Focus on Radiation Protection Improves Both Correct Behavior and Procedural Performance During Simulation-Based Training - A Randomized Comparison.

BACKGROUND: To explore whether simulation-based endovascular training with focus on radiation safety could improve correct behavior without jeopardizing the learning of procedural skills. METHODS: Twenty-four residents without previous endovascular experience completed 10 clinical scenarios on a virtual-reality endovascular simulator with software for peripheral endovascular interventions. Participants were randomized to receive feedback (n = 12) or not (n = 12) on radiation protection (RP) performance after each case. Expert assessments were done at the first, second, fourth, seventh, and 10th case on RP and endovascular skills (ES). Automatic simulator metrics on procedure time, contrast dose, handling errors, and estimated radiation exposure to patient and operator were registered. Outcome metrics were analyzed by two-way mixed analysis of variance pairwise comparisons with independent t-tests. Correlations were explored using Pearson's r for internal consistency reliability. RESULTS: The RP performance was similar in both groups at their first attempt (P = 0.61), but the feedback group significantly outperformed the control group over time (P < 0.001 for all comparisons). The feedback group was however slower to learn the ES at start (P = 0.047 at second performance), but after 7 attempts no difference was shown (P = 0.59). The feedback group used more time (19.5 vs. 15.3 min; P = 0.007) but less contrast (60 vs. 100 mL; P < 0.001). The number of errors was the same in both groups, but all metrics regarding radiation exposure favored the feedback group (P-values from 0.001 to 0.008). CONCLUSIONS: Simulation-based training (SBT) is effective to acquire basic endovascular intervention skills and concurrently learn RP behavior when feedback on radiation culture is provided.

Phase Unwrapping Error Correction Based on Multiple Linear Regression Analysis.

Fringe projection profilometry (FPP) is prone to phase unwrapping error (PUE) due to phase noise and measurement conditions. Most of the existing PUE-correction methods detect and correct PUE on a pixel-by-pixel or partitioned block basis and do not make full use of the correlation of all information in the unwrapped phase map. In this study, a new method for detecting and correcting PUE is proposed. First, according to the low rank of the unwrapped phase map, multiple linear regression analysis is used to obtain the regression plane of the unwrapped phase, and thick PUE positions are marked on the basis of the tolerance set according to the regression plane. Then, an improved median filter is used to mark random PUE positions and finally correct marked PUE. Experimental results show that the proposed method is effective and robust. In addition, this method is progressive in the treatment of highly abrupt or discontinuous regions.

Robust Point Cloud Registration Network for Complex Conditions.

Point cloud registration is widely used in autonomous driving, SLAM, and 3D reconstruction, and it aims to align point clouds from different viewpoints or poses under the same coordinate system. However, point cloud registration is challenging in complex situations, such as a large initial pose difference, high noise, or incomplete overlap, which will cause point cloud registration failure or mismatching. To address the shortcomings of the existing registration algorithms, this paper designed a new coarse-to-fine registration two-stage point cloud registration network, CCRNet, which utilizes an end-to-end form to perform the registration task for point clouds. The multi-scale feature extraction module, coarse registration prediction module, and fine registration prediction module designed in this paper can robustly and accurately register two point clouds without iterations. CCRNet can link the feature information between two point clouds and solve the problems of high noise and incomplete overlap by using a soft correspondence matrix. In the standard dataset ModelNet40, in cases of large initial pose difference, high noise, and incomplete overlap, the accuracy of our method, compared with the second-best popular registration algorithm, was improved by 7.0%, 7.8%, and 22.7% on the MAE, respectively. Experiments showed that our CCRNet method has advantages in registration results in a variety of complex conditions.

Budesonide-liposomes inclusion complex in thermosensitive gel alleviates DSS-induced ulcerative colitis in mice.

PURPOSE: A novel formulation for Ulcerative Colitis (UC) treatment by rectal administration with budesonide liposomes (Bud Lip) and thermosensitive gel (Gel) was developed for future clinical use. To evaluate the anti-inflammatory activity and colon mucosal protection of this novel formulation compared with the other three in mice. METHODS: Bud Lip was prepared by reverse evaporation method and then dispersed in solutions with PL407 and PL188 by a cold method. Male mice were induced to UC by dextran sulfate sodium (DSS) and were treated for 14 days by rectal administration, as follows: Bud enema (a conventional suspension formulation); Bud Lip; Bud Gel; Bud Lip-Gel; saline. And a negative control without colitis was also used. Disease activity index (DAI), and macroscopic and microscopic damage scores in colon tissues were used to evaluate the effect of therapy. The levels of IL-6 and IL-10 in serum and the concentrations of TNF-α and IL-10 and myeloperoxidase (MPO) activity in colon tissue were also introduced. RESULTS: In UC mice model, Bud Lip-Gel showed inflammation was alleviated significantly, and the treatment was highly associated with lower DAI, less macroscopic and microscopic colonic damage and downregulation of pro-inflammatory cytokines TNF-α, IL-6 and MPO. Bud Lip-Gel had advantages over Bud, Bud Lip, Bud Gel in the treatment of active UC. CONCLUSION: Novel Bud liposomes complex in thermosensitive Gel effectively mitigated symptoms, alleviated macroscopic and microscopic colon damage, and reduced inflammatory reaction in UC mice, which might be a potential strategy for UC treatment.

[Research progress on Rhododendron molle in treatment of rheumatoid arthritis].

Rheumatoid arthritis(RA), as a chronic autoimmune disease, has a high incidence and disability rate, causing significant suffering to patients. Due to its complex pathogenesis, it has not been fully elucidated to date, and its treatment remains a challenging problem in the medical field. Although western medicine treatment options have certain efficacy, they require prolonged use and are expensive. Additionally, they carry risks of multiple infections and adverse reactions like malignancies. The Chinese herbal medicine Rhododendron molle is commonly used in folk medicine for its properties of dispelling wind, removing dampness, calming nerves, and alleviating pain in the treatment of diseases like rheumatic bone diseases. In recent years, modern clinical and pharmacological studies have shown that the diterpenoids in R. molle are effective components, exhibiting immune-regulatory, anti-inflammatory, and analgesic effects. This makes it a promising candidate for treating RA with a broad range of potential applications. However, R. molle has certain toxic properties that hinder its clinical application and lead to the wastage of its resources. This study reviewed recent research progress on the mechanism of R. molle in preventing and treating RA, focusing on its chemical components, anti-inflammatory and analgesic properties and summarized the adverse reactions associated with R. molle, aiming to offer new ideas for finding natural remedies for RA and methods to reduce toxicity while enhancing the effectiveness of R. molle. The study seeks to clarify the safety and efficacy of R. molle and its extracts, providing a theoretical basis for its application prospects and further promoting the development and utilization of R. molle resources.

Estimating global and regional disruptions to routine childhood vaccine coverage during the COVID-19 pandemic in 2020: a modelling study.

BACKGROUND: The COVID-19 pandemic and efforts to reduce SARS-CoV-2 transmission substantially affected health services worldwide. To better understand the impact of the pandemic on childhood routine immunisation, we estimated disruptions in vaccine coverage associated with the pandemic in 2020, globally and by Global Burden of Disease (GBD) super-region. METHODS: For this analysis we used a two-step hierarchical random spline modelling approach to estimate global and regional disruptions to routine immunisation using administrative data and reports from electronic immunisation systems, with mobility data as a model input. Paired with estimates of vaccine coverage expected in the absence of COVID-19, which were derived from vaccine coverage models from GBD 2020, Release 1 (GBD 2020 R1), we estimated the number of children who missed routinely delivered doses of the third-dose diphtheria-tetanus-pertussis (DTP3) vaccine and first-dose measles-containing vaccine (MCV1) in 2020. FINDINGS: Globally, in 2020, estimated vaccine coverage was 76·7% (95% uncertainty interval 74·3-78·6) for DTP3 and 78·9% (74·8-81·9) for MCV1, representing relative reductions of 7·7% (6·0-10·1) for DTP3 and 7·9% (5·2-11·7) for MCV1, compared to expected doses delivered in the absence of the COVID-19 pandemic. From January to December, 2020, we estimated that 30·0 million (27·6-33·1) children missed doses of DTP3 and 27·2 million (23·4-32·5) children missed MCV1 doses. Compared to expected gaps in coverage for eligible children in 2020, these estimates represented an additional 8·5 million (6·5-11·6) children not routinely vaccinated with DTP3 and an additional 8·9 million (5·7-13·7) children not routinely vaccinated with MCV1 attributable to the COVID-19 pandemic. Globally, monthly disruptions were highest in April, 2020, across all GBD super-regions, with 4·6 million (4·0-5·4) children missing doses of DTP3 and 4·4 million (3·7-5·2) children missing doses of MCV1. Every GBD super-region saw reductions in vaccine coverage in March and April, with the most severe annual impacts in north Africa and the Middle East, south Asia, and Latin America and the Caribbean. We estimated the lowest annual reductions in vaccine delivery in sub-Saharan Africa, where disruptions remained minimal throughout the year. For some super-regions, including southeast Asia, east Asia, and Oceania for both DTP3 and MCV1, the high-income super-region for DTP3, and south Asia for MCV1, estimates suggest that monthly doses were delivered at or above expected levels during the second half of 2020. INTERPRETATION: Routine immunisation services faced stark challenges in 2020, with the COVID-19 pandemic causing the most widespread and largest global disruption in recent history. Although the latest coverage trajectories point towards recovery in some regions, a combination of lagging catch-up immunisation services, continued SARS-CoV-2 transmission, and persistent gaps in vaccine coverage before the pandemic still left millions of children under-vaccinated or unvaccinated against preventable diseases at the end of 2020, and these gaps are likely to extend throughout 2021. Strengthening routine immunisation data systems and efforts to target resources and outreach will be essential to minimise the risk of vaccine-preventable disease outbreaks, reach children who missed routine vaccine doses during the pandemic, and accelerate progress towards higher and more equitable vaccination coverage over the next decade. FUNDING: Bill & Melinda Gates Foundation.

Changes in esophagus interstitial cells of Cajal in response to acute stress.

BACKGROUND: Thoracic trauma is common, and traffic accident-related traumatic injury can cause acute stress leading to esophageal motility disorders. Interstitial cells of Cajal (ICCs) are regarded as gastrointestinal pacemaker cells. AIM: This study explored the mechanism underlying changes in lower esophagus ICCs under acute stress conditions. METHODS: Fifty adult rabbits, randomly divided into one healthy control and four study groups, were subjected to right chest puncture using a Hopkinson bar. Thereafter, one group was immediately subjected to lower esophagectomy, whereas the other three groups were maintained for 24, 48 and 72 h after puncture and subjected to lower esophagectomy. Immunohistochemistry was used to detect ICC distribution, morphology and density, and TUNEL assays were used to determine ICC apoptosis. Enzyme-linked immunosorbent assays (ELISAs) were used to measure cortisol, epinephrine, dopamine, IL-9, cholecystokinin (CCK) and vasoactive intestinal peptide (VIP). Western blotting and RT-PCR were performed to detect changes in SCF/c-kit and nNOS pathways. RESULTS: After puncture, lung tissue was hemorrhaged, alveoli in puncture areas were destroyed, esophageal pH was decreased, and serum cortisol, epinephrine and dopamine levels increased. ICC numbers increased and apoptotic ICCs decreased in all stress groups after puncture (all p < .01). IL-9, CCK and VIP levels in lower esophagus tissue were increased after puncture (all p < .01). Moreover, SCF/c-kit and nNOS pathways were upregulated in response to stress (all p < .01). CONCLUSIONS: Acute stress promotes increases in lower esophageal ICCs that might affect esophagus ICC functions and esophageal motility.

Etiology and genetic evolution of canine coronavirus circulating in five provinces of China, during 2018-2019.

As the outbreaks of COVID-19 in worldwide, coronavirus has once again caught the attention of people. Canine coronavirus is widespread among dog population, and sometimes causes even fatal cases. Here, to characterize the prevalence and evolution of current circulating canine coronavirus (CCoV) strains in China, we collected 213 fecal samples from diarrheic pet dogs between 2018 and 2019. Of the 213 samples, we found 51 (23.94%) were positive for CCoV. Co-infection with canine parvovirus (CPV), canine astrovirus (CaAstV), canine kobuvirus (CaKV), Torque teno canis virus (TTCaV) were ubiquitous existed. Mixed infection of different CCoV subtypes exists extensively. Considering the limited sequences data in recent years, we sequenced 7 nearly complete genomes and 10 complete spike gene. Phylogenetic analysis of spike gene revealed a new subtype CCoV-II Variant and CCoV-IIa was the most prevalent subtype currently circulating. Moreover, we identified strain B906_ZJ_2019 shared 93.24% nucleotide identifies with previous strain A76, and both of them clustered with CCoV-II Variant, which were not well clustered with the known subtypes. Recombination analysis of B906_ZJ_2019 indicated that strain B906_ZJ_2019 may a recombinant variant between CCoV-I and CCoV-II, which is consistent with strain A76. Furthermore, amino acid variations widely existed among current CCoV-IIa strains circulating in China and the classic CCoV-IIa strains, in spite of the unknown functions. In a word, we report a useful information as to the etiology and evolution of canine coronavirus in China based on the available sequences, which is urgent for the devise of future effective disease prevention and control strategies.

Anion-Coordination-Assisted Assembly of Supramolecular Charge-Transfer Complexes Based on Tris(urea) Ligands.

Charge-transfer (CT) complexes, formed by noncovalent bonding between electron-rich (donor, D) and electron-deficient (acceptor, A) molecules (or moieties) have attracted considerable attention due to their fascinating structures and potential applications. Herein, we demonstrate that anion coordination is a promising strategy to promote CT complex formation between anion-binding, electron-rich tris(urea) donor ligands (D) and electron-deficient viologen cation acceptors (A), which form co-crystals featuring infinite ⋅⋅⋅DADA⋅⋅⋅ or discrete (circular DADA or three-decker DAD) π-stacking interactions. These CT complexes were studied by X-ray diffraction, UV/Vis spectroscopy, electric conductivity measurements, charge displacement curve (CDC) calculations, and DFT computations.

Impact of hydrogen dopant incorporation on InGaZnO, ZnO and In2O3 thin film transistors.

In this work, hydrogen (H) plasma treatment is implemented to dope indium gallium zinc oxide (InGaZnO), zinc oxide (ZnO), and indium oxide (In2O3) thin-film transistors (TFTs). We systematically analyze the active defect states inside these n-type metal oxides and reveal how they are impacted by H dopant incorporation, combining the device transfer characteristics (including the threshold voltage, subthreshold slope, and carrier mobility), the X-ray photoelectron spectra, and numerical and theoretical investigations. An increase of the field-effect mobility of these TFTs is mainly attributed to the decreased interface and bulk tail-distributed traps, after an appropriate amount of H dopants is incorporated. In ZnO, hydrogen exclusively acts as a shallow donor during the plasma treatment, while the zinc vacancies Zn(Vac) cannot be passivated by the H dopants as no improvement of the subthreshold slope (SS) is observed in the hydrogenated ZnO TFT. The H interstitials (Hi) incorporated into In2O3 are stable in the + charge state at equilibrium, then change into the - charge state as the Fermi level energy EF gets closer to the bottom of the conduction band. Due to the H insertion into an oxygen vacancy VO, the VOH complex (acting as an acceptor) is formed in InGaZnO with increased H plasma treatment duration, leading to the degraded SS. This paper clarifies the H dopants' role and the different dominant defects inside the three types of TFTs, which may benefit systematic understanding and exploration of H dopant incorporation into InGaZnO, ZnO and In2O3 films for TFT improvement and optimization.

Effects of Marital Status on Prognosis in Women with Infiltrating Ductal Carcinoma of the Breast: A Real-World 1: 1 Propensity-Matched Study.

BACKGROUND The effects of marital status on infiltrating ductal carcinoma of breast cancer (IDC) have not been studied in detail. This study investigated the impact of marital status on IDC patients. MATERIAL AND METHODS SEER databases were searched from 2010 to 2015 for subjects who were married, divorced, single, and widowed. The influence of marital status on breast cancer-specific survival (BCSS) and overall survival (OS) of IDC patients was investigated through multivariate Cox regression analysis and Kaplan-Meier analysis. To prevent bias, propensity score matching (PSM) analysis was performed. RESULTS The 5-year OS was 89.6%in married patients, 84.9% in divorced patients, 83.5% in single patients, and 71.3% in widowed patients (p<0.001). The 5-year BCSS were 92.9%, 90.2%, 87.6%, and 86.4%, respectively (p<0.001). Multivariate Cox regression analysis revealed that marriage was a protective factor for patients with IDC in terms of OS (divorced: HR, 1.27; 95% CI, 1.21-1.32; p<0.001; single: HR, 1.36; 95% CI, 1.31-1.42; p<0.001; widowed: HR, 1.42; 95% CI, 1.36-1.48; p<0.001) and BCSS (divorced: HR, 1.15; 95% CI, 1.09-1.21; p<0.001; single: HR, 1.27; 95% CI, 1.21-1.33; p<0.001; widowed: HR, 1.32; 95% CI, 1.25-1.40; p<0.001). Following subgroup and PSM analysis, married patients were shown to have better OS and BCSS as opposed to divorced, single, or widowed patients. CONCLUSIONS We identify marital status as a predictor of survival in those with IDC. Widowed patients showed the highest mortality risk.

Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories.

BACKGROUND: Understanding potential trajectories in health and drivers of health is crucial to guiding long-term investments and policy implementation. Past work on forecasting has provided an incomplete landscape of future health scenarios, highlighting a need for a more robust modelling platform from which policy options and potential health trajectories can be assessed. This study provides a novel approach to modelling life expectancy, all-cause mortality and cause of death forecasts -and alternative future scenarios-for 250 causes of death from 2016 to 2040 in 195 countries and territories. METHODS: We modelled 250 causes and cause groups organised by the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) hierarchical cause structure, using GBD 2016 estimates from 1990-2016, to generate predictions for 2017-40. Our modelling framework used data from the GBD 2016 study to systematically account for the relationships between risk factors and health outcomes for 79 independent drivers of health. We developed a three-component model of cause-specific mortality: a component due to changes in risk factors and select interventions; the underlying mortality rate for each cause that is a function of income per capita, educational attainment, and total fertility rate under 25 years and time; and an autoregressive integrated moving average model for unexplained changes correlated with time. We assessed the performance by fitting models with data from 1990-2006 and using these to forecast for 2007-16. Our final model used for generating forecasts and alternative scenarios was fitted to data from 1990-2016. We used this model for 195 countries and territories to generate a reference scenario or forecast through 2040 for each measure by location. Additionally, we generated better health and worse health scenarios based on the 85th and 15th percentiles, respectively, of annualised rates of change across location-years for all the GBD risk factors, income per person, educational attainment, select intervention coverage, and total fertility rate under 25 years in the past. We used the model to generate all-cause age-sex specific mortality, life expectancy, and years of life lost (YLLs) for 250 causes. Scenarios for fertility were also generated and used in a cohort component model to generate population scenarios. For each reference forecast, better health, and worse health scenarios, we generated estimates of mortality and YLLs attributable to each risk factor in the future. FINDINGS: Globally, most independent drivers of health were forecast to improve by 2040, but 36 were forecast to worsen. As shown by the better health scenarios, greater progress might be possible, yet for some drivers such as high body-mass index (BMI), their toll will rise in the absence of intervention. We forecasted global life expectancy to increase by 4·4 years (95% UI 2·2 to 6·4) for men and 4·4 years (2·1 to 6·4) for women by 2040, but based on better and worse health scenarios, trajectories could range from a gain of 7·8 years (5·9 to 9·8) to a non-significant loss of 0·4 years (-2·8 to 2·2) for men, and an increase of 7·2 years (5·3 to 9·1) to essentially no change (0·1 years [-2·7 to 2·5]) for women. In 2040, Japan, Singapore, Spain, and Switzerland had a forecasted life expectancy exceeding 85 years for both sexes, and 59 countries including China were projected to surpass a life expectancy of 80 years by 2040. At the same time, Central African Republic, Lesotho, Somalia, and Zimbabwe had projected life expectancies below 65 years in 2040, indicating global disparities in survival are likely to persist if current trends hold. Forecasted YLLs showed a rising toll from several non-communicable diseases (NCDs), partly driven by population growth and ageing. Differences between the reference forecast and alternative scenarios were most striking for HIV/AIDS, for which a potential increase of 120·2% (95% UI 67·2-190·3) in YLLs (nearly 118 million) was projected globally from 2016-40 under the worse health scenario. Compared with 2016, NCDs were forecast to account for a greater proportion of YLLs in all GBD regions by 2040 (67·3% of YLLs [95% UI 61·9-72·3] globally); nonetheless, in many lower-income countries, communicable, maternal, neonatal, and nutritional (CMNN) diseases still accounted for a large share of YLLs in 2040 (eg, 53·5% of YLLs [95% UI 48·3-58·5] in Sub-Saharan Africa). There were large gaps for many health risks between the reference forecast and better health scenario for attributable YLLs. In most countries, metabolic risks amenable to health care (eg, high blood pressure and high plasma fasting glucose) and risks best targeted by population-level or intersectoral interventions (eg, tobacco, high BMI, and ambient particulate matter pollution) had some of the largest differences between reference and better health scenarios. The main exception was sub-Saharan Africa, where many risks associated with poverty and lower levels of development (eg, unsafe water and sanitation, household air pollution, and child malnutrition) were projected to still account for substantive disparities between reference and better health scenarios in 2040. INTERPRETATION: With the present study, we provide a robust, flexible forecasting platform from which reference forecasts and alternative health scenarios can be explored in relation to a wide range of independent drivers of health. Our reference forecast points to overall improvements through 2040 in most countries, yet the range found across better and worse health scenarios renders a precarious vision of the future-a world with accelerating progress from technical innovation but with the potential for worsening health outcomes in the absence of deliberate policy action. For some causes of YLLs, large differences between the reference forecast and alternative scenarios reflect the opportunity to accelerate gains if countries move their trajectories toward better health scenarios-or alarming challenges if countries fall behind their reference forecasts. Generally, decision makers should plan for the likely continued shift toward NCDs and target resources toward the modifiable risks that drive substantial premature mortality. If such modifiable risks are prioritised today, there is opportunity to reduce avoidable mortality in the future. However, CMNN causes and related risks will remain the predominant health priority among lower-income countries. Based on our 2040 worse health scenario, there is a real risk of HIV mortality rebounding if countries lose momentum against the HIV epidemic, jeopardising decades of progress against the disease. Continued technical innovation and increased health spending, including development assistance for health targeted to the world's poorest people, are likely to remain vital components to charting a future where all populations can live full, healthy lives. FUNDING: Bill & Melinda Gates Foundation.

Self-management interventions for chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Self-management intervention aims to facilitate an individual's ability to make lifestyle changes. The effectiveness of this intervention in non-dialysis patients with chronic kidney disease (CKD) is limited. In this study, we applied a systematic review and meta-analysis to investigate whether self-management intervention improves renoprotection for non-dialysis chronic kidney disease. METHODS: We conducted a comprehensive search for randomized controlled trials addressing our objective. We searched for studies up to May 12, 2018. Two reviewers independently evaluated study quality and extracted characteristics and outcomes among patients with CKD within the intervention phase for each trial. Meta-regression and subgroup analyses were conducted to explore heterogeneity. RESULTS: We identified 19 studies with a total of 2540 CKD patients and a mean follow-up of 13.44 months. Compared with usual care, self-management intervention did not show a significant difference for risk of all-cause mortality (5 studies, 1662 participants; RR 1.13; 95% CI 0.68 to 1.86; I2 = 0%), risk of dialysis (5 studies, 1565 participants; RR 1.35; 95% CI 0.84 to 2.19; I2 = 0%), or change in eGFR (8 studies, 1315 participants; SMD -0.01; 95% CI -0.23 to 0.21; I2 = 64%). Moreover, self-management interventions were associated with a lower 24 h urinary protein excretion (4 studies, 905 participants; MD - 0.12 g/24 h; 95% CI -0.21 to - 0.02; I2 = 3%), a lower blood pressure level (SBP: 7 studies, 1201 participants; MD - 5.68 mmHg; 95%CI - 9.68 to - 1.67; I2 = 60%; DBP: 7 studies, 1201 participants; MD - 2.64 mmHg, 95% CI -3.78 to - 1.50; I2 = 0%), a lower C-reactive Protein (CRP) level (3 studies, 123 participants; SMD -2.8; 95% CI -2.90 to - 2.70; I2 = 0%) and a longer distance on the 6-min walk (3 studies, 277 participants; SMD 0.70; 95% CI 0.45 to 0.94; I2 = 0%) when compared with the control group. CONCLUSIONS: We observed that self-management intervention was beneficial for urine protein decline, blood pressure level, exercise capacity and CRP level, compared with the standard treatment, during a follow-up of 13.44 months in patients with CKD non-dialysis. However, it did not provide additional benefits for renal outcomes and all-cause mortality.

The prognostic value of tumor-infiltrating lymphocytes in colorectal cancer differs by anatomical subsite: a systematic review and meta-analysis.

PURPOSE: In colorectal cancer (CRC), whether the immune score can be used to predict the clinical prognosis of the patient has not been completely established. Besides, the prognostic values of tumor-infiltrating lymphocytes (TILs) in different anatomical locations, counting sites, and subtypes have been controversial. The purpose of this meta-analysis is to analyze and determine the prognostic value of TILs indices including TIL subsets, infiltrating sites, and anatomical sites. METHODS: Relevant literature was obtained by searching PubMed and Google Scholar. The pooled hazard ratio (HR) of the overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) was computed to investigate the prognostic significance of CD3+, CD8+, CD45RO+, and FOXP3+ T cells. RESULTS: A total of 22 studies involving 5108 patients were included in the meta-analysis. In CC, based on T cell subtypes analysis, the final results indicated that CD8+ and FOXP3+ infiltrating cells, but not CD3+ T cells were prognostic markers for DFS and OS. In addition, with regard to the counting location of TILs, subgroup analysis revealed that only high FOXP3+ infiltrates in the tumor stroma (ST) were significantly associated with OS (HR = 0.38, 95% confidence interval (CI) = 0.22-0.67, P = 0.0007), whereas in invasive margin (IM), high density of CD3+ infiltrating cells indicated increased DFS (HR = 0.76, 95% CI = 0.62-0.93, P = 0.008). At the tumor center (TC), high CD8+ T cells infiltration was associated with improved DFS (HR = 0.50, 95% CI = 0.38-0.65, P < 0.00001). In RC, whether CSS or OS, high-density TIL was associated with improved prognosis. CONCLUSION: In a single counting site, high-density TILs reflect favorable prognostic value in CC or RC. For CC, more prospective studies are needed to verify whether different anatomical sites affect the distribution of TILs and thus the prognosis of patients. For RC, further studies should analyze the prognostic value of the immune score.