Comparison of implant placement and loading protocols for single anterior maxillary implants: A systematic review and network meta-analysis.

STATEMENT OF PROBLEM: With increasing esthetic needs, patients prefer missing anterior teeth to be restored as soon as possible, but how the timing of implantation and prosthetic loading influences peri-implant tissue and the esthetic results remains unclear. PURPOSE: The purpose of this systematic review and network meta-analysis of randomized controlled trials was to investigate and rank the hard-tissue and soft-tissue outcomes, esthetics, and patient satisfaction of single maxillary implant placement and loading protocols. MATERIAL AND METHODS: A systematic search was conducted to identify studies with at least a 1-year follow-up that compared different implant placement and loading protocols and reported on survival, marginal bone loss (MBL), soft tissue, and esthetics. A random effects model and a Bayesian approach were applied to compare protocols by using mean differences (MD) with 95% credible intervals (CrI) and surface under the cumulative ranking curve (SUCRA) values. RESULTS: A total of 43 articles were included, with a follow-up of 1 to 5 years. All protocols had high survival rates and no significant differences for 1-year or 2-year MBL. Immediate placement with immediate loading ranked first in pink and white esthetic scores and satisfaction and was statistically significantly better than immediate placement with delayed loading or late placement protocols in pink esthetic scores, where its advantage over late placement with late loading was also clinically relevant [MD: -1.74, CrI: -2.34 to -1.15]. CONCLUSIONS: Immediate implantation with immediate loading showed a considerable esthetic advantage over later rehabilitation, whereas only a slight difference in MBL resulted from different protocols.

Phellinus igniarius Polysaccharides Ameliorate Hyperglycemia by Modulating the Composition of the Gut Microbiota and Their Metabolites in Diabetic Mice.

Gut microbiota dysbiosis has been reported as a risk factor in the development of type 2 diabetes mellitus (T2DM). Polysaccharides from Phellinus igniarius (P. igniarius) possess various properties that help manage metabolic diseases; however, their underlying mechanism of action remains unclear. Therefore, in this study, we aimed to evaluate the effect of P. igniarius polysaccharides (SH-P) on improving hyperglycemia in mice with T2DM and clarified its association with the modulation of gut microbiota and their metabolites using 16S rDNA sequencing and liquid chromatography-mass spectrometry. Fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling. SH-P supplementation alleviated hyperglycemia symptoms in T2DM mice, ameliorated gut dysbiosis, and significantly increased the abundance of Lactobacillus in the gut. Pathway enrichment analysis indicated that SH-P treatment altered metabolic pathways associated with the occurrence and development of diabetes. Spearman's correlation analysis revealed that changes in the dominant bacterial genera were significantly correlated with metabolite levels closely associated with hyperglycemia. Additionally, FMT significantly improved insulin sensitivity and antioxidative capacity and reduced inflammation and tissue injuries, indicating improved glucose homeostasis. These results indicate that the ameliorative effects of SH-P on hyperglycemia are associated with the modulation of gut microbiota composition and its metabolites.

Methods and resources to access mutation-dependent effects on cancer drug treatment.

In clinical cancer treatment, genomic alterations would often affect the response of patients to anticancer drugs. Studies have shown that molecular features of tumors could be biomarkers predictive of sensitivity or resistance to anticancer agents, but the identification of actionable mutations are often constrained by the incomplete understanding of cancer genomes. Recent progresses of next-generation sequencing technology greatly facilitate the extensive molecular characterization of tumors and promote precision medicine in cancers. More and more clinical studies, cancer cell lines studies, CRISPR screening studies as well as patient-derived model studies were performed to identify potential actionable mutations predictive of drug response, which provide rich resources of molecularly and pharmacologically profiled cancer samples at different levels. Such abundance of data also enables the development of various computational models and algorithms to solve the problem of drug sensitivity prediction, biomarker identification and in silico drug prioritization by the integration of multiomics data. Here, we review the recent development of methods and resources that identifies mutation-dependent effects for cancer treatment in clinical studies, functional genomics studies and computational studies and discuss the remaining gaps and future directions in this area.

[Conversion of ISO 7439:2015 Copper-bearing Contraceptive Intrauterine Devices - Requirements and Tests Standard Analysis].

This paper introduces the basic content of the compulsory national standard ISO 7439:2015 Copper-bearing contraceptive intrauterine devices--Requirements and tests standard analysis, and expounds the reasons for revising part of the standard during the conversion process according to the actual market situation of intrauterine contraceptive device containing copper in China. As a compulsory basic universal standard, it has a guiding significance for the manufacturers of IUD and can promote the improvement of product quality.

DriverML: a machine learning algorithm for identifying driver genes in cancer sequencing studies.

Although rapid progress has been made in computational approaches for prioritizing cancer driver genes, research is far from achieving the ultimate goal of discovering a complete catalog of genes truly associated with cancer. Driver gene lists predicted from these computational tools lack consistency and are prone to false positives. Here, we developed an approach (DriverML) integrating Rao's score test and supervised machine learning to identify cancer driver genes. The weight parameters in the score statistics quantified the functional impacts of mutations on the protein. To obtain optimized weight parameters, the score statistics of prior driver genes were maximized on pan-cancer training data. We conducted rigorous and unbiased benchmark analysis and comparisons of DriverML with 20 other existing tools in 31 independent datasets from The Cancer Genome Atlas (TCGA). Our comprehensive evaluations demonstrated that DriverML was robust and powerful among various datasets and outperformed the other tools with a better balance of precision and sensitivity. In vitro cell-based assays further proved the validity of the DriverML prediction of novel driver genes. In summary, DriverML uses an innovative, machine learning-based approach to prioritize cancer driver genes and provides dramatic improvements over currently existing methods. Its source code is available at https://github.com/HelloYiHan/DriverML.

Long noncoding RNA LCAT1 functions as a ceRNA to regulate RAC1 function by sponging miR-4715-5p in lung cancer.

INTRODUCTION: Long noncoding RNAs (lncRNAs) are emerging as key players in the development and progression of cancer. However, the biological role and clinical significance of most lncRNAs in lung carcinogenesis remain unclear. In this study, we identified and explored the role of a novel lncRNA, lung cancer associated transcript 1 (LCAT1), in lung cancer. METHODS: We predicted and validated LCAT1 from RNA-sequencing (RNA-seq) data of lung cancer tissues. The LCAT1-miR-4715-5p-RAC1 axis was assessed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Signaling pathways altered by LCAT1 knockdown were identified using RNA-seq. Furthermore, the mechanism of LCAT1 was investigated using loss-of-function and gain-of-function assays in vivo and in vitro. RESULTS: LCAT1 is an oncogene that is significantly upregulated in lung cancer tissues and associated with poor prognosis. LCAT1 knockdown caused growth arrest and cell invasion in lung cancer cells in vitro, and inhibited tumorigenesis and metastasis in the mouse xenografts. Mechanistically, LCAT1 functions as a competing endogenous RNA for miR-4715-5p, thereby leading to the upregulation of the activity of its endogenous target, Rac family small GTPase 1 (RAC1). Moreover, EHop-016, a small molecule inhibitor of RAC1, as an adjuvant could improve the Taxol monotherapy against lung cancer cells in vitro. CONCLUSIONS: LCAT1-miR-4715-5p-RAC1/PAK1 axis plays an important role in the progression of lung cancer. Our findings may provide valuable drug targets for treating lung cancer. The novel combination therapy of Taxol and EHop-016 for lung cancer warrants further investigation, especially in lung cancer patients with high LCAT1 expression.

Microbially-induced Carbonate Precipitation for Immobilization of Toxic Metals.

Rapid urbanization and industrialization resulting from growing populations contribute to environmental pollution by toxic metals and radionuclides which pose a threat to the environment and to human health. To combat this threat, it is important to develop remediation technologies based on natural processes that are sustainable. In recent years, a biomineralization process involving ureolytic microorganisms that leads to calcium carbonate precipitation has been found to be effective in immobilizing toxic metal pollutants. The advantage of using ureolytic organisms for bioremediating metal pollution in soil is their ability to immobilize toxic metals efficiently by precipitation or coprecipitation, independent of metal valence state and toxicity and the redox potential. This review summarizes current understanding of the ability of ureolytic microorganisms for carbonate biomineralization and applications of this process for toxic metal bioremediation. Microbial metal carbonate precipitation may also be relevant to detoxification of contaminated process streams and effluents as well as the production of novel carbonate biominerals and biorecovery of metals and radionuclides that form insoluble carbonates.

Using the Dynamic Model of Affect (DMA) to examine leisure time as a stress coping resource: Taking into account stress severity and gender difference.

Affective complexity (AC) is a marker of psychological well-being. According to the Dynamic Model of Affect (DMA), stressful experiences reduce AC while positive events increase AC. One type of positive events is leisure, which was also identified as a coping resource. This study extended the DMA and leisure coping research by assessing gender difference in how daily stress severity and leisure time influence AC. Analyzing eight-day diary data, we found that females, compared to males, experienced greater decrease in AC with increase in stress severity but also bigger increase in AC with increase in leisure time. The finding highlights gender difference in affective reactivity to and coping with daily stress, the value of the DMA, and the importance of severity appraisal.

Does leisure time moderate or mediate the effect of daily stress on positive affect? An examination using eight-day diary data.

This study tested the applicability of moderation and mediation models to leisure time as a stress coping resource. Analyzing eight-day diary data (N=2,022), we examined the within-person process of using leisure time to cope with daily stressors. We found that relatively high daily stress frequency, while reducing positive affect, prompted an individual to allocate more time to leisure than usual, which then increased positive affect, thus partially remedying the damage by high daily stress frequency. This within-person process, however, is significantly stronger among those with less leisure time on average than leisure-rich individuals. The findings support a partial counteractive mediation model, demonstrate between-person difference in the within-person coping process, and reveal the importance of positive affect as a coping outcome.

Building microcracked structure fibrous cathode coated by Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) for ultra-stable fiber-shaped aqueous zinc ions batteries.

Attributing to the advantages of intrinsic safety, high energy density, and good omnidirectional flexibility, fiber-shaped aqueous zinc ions batteries (FAZIBs), serving as energy supply devices, have multitude applications in flexible and wearable electronic devices. However, the detachment of active materials caused by bending stress generated during flexing process limits their practical application severely. To address the above issue, an effective integrated strategy employing microcracked activated cobalt hydroxide [A-Co(OH)2] cathode with protective coating of poly(3,4-ethylenedioxythiophene)poly(styrenesulfonate) (PEDOT:PSS) was proposed in this work to enhance the cyclic and bending performances of FAZIBs. The microcracked A-Co(OH)2 cathode relieves stress concentration under bending conditions, while the PEDOT:PSS coating is responsible to maintain the structural integrity and prevents the detachment of A-Co(OH)2. The FAZIBs based on a gel electrolyte achieved a high energy density (173.5 Wh·kg-1) at a power density 90 W·kg-1 and a bending durability (94.4 % capacity retention after 500 cycles) as a consequence of the synergistic effect of microcracked A-Co(OH)2 cathode and the PEDOT:PSS coating. This work will offer a new approach for devising high-performance FAZIBs and promote the development of highly flexible and stable fiber-shaped batteries.

Does Leisure Time as a Stress Coping Resource Increase Affective Complexity? Applying the Dynamic Model of Affect (DMA).

Affective complexity, a manifestation of psychological well-being, refers to the relative independence between positive and negative affect (PA, NA). According to the Dynamic Model of Affect (DMA), stressful situations lead to highly inverse PA-NA relationship, reducing affective complexity. Meanwhile, positive events can sustain affective complexity by restoring PA-NA independence. Leisure, a type of positive events, has been identified as a coping resource. This study used the DMA to assess whether leisure time helps restore affective complexity on stressful days. We found that on days with more leisure time than usual, an individual experienced less negative PA-NA relationship after daily stressful events. The finding demonstrates the value of leisure time as a coping resource and the DMA's contribution to coping research.

Effects of 10 Hz individualized repetitive transcranial magnetic stimulation on patients with disorders of consciousness: a study protocol for an exploratory double-blind crossover randomized sham-controlled trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive brain stimulation technique, has shown potentials for consciousness recovery of patients with disorders of consciousness (DoC), as, to a certain extent, it is effective in regulating the excitability of central nervous system. However, it is difficult to achieve satisfactory effect with "one size fits all" rTMS treatment due to different clinical conditions of patients. There is an urgent need to develop individualized strategy to improve the effectiveness of rTMS on patients with DoC. METHODS: Our protocol is a randomized double-blind sham-controlled crossover trial that includes 30 DoC patients. Each patient will received 20 sessions, in which 10 sessions will be rTMS-active stimulus, and the other 10 sessions will be sham stimulus, separated by no less than 10 days' washout period. The rTMS-active will include 10 Hz rTMS over the individualized-targeted selection area for each patient according to the different insult regions of the brain. Coma Recovery Scale-Revised (CRS-R) will be used as primary outcome at baseline, after the first stage of stimulation, at the end of the washout period, and after the second stage of stimulation. Secondary outcomes will be measured at the same time, including efficiency, relative spectral power, and functional connectivity of high-density electroencephalograph (EEG). Adverse events will be recorded during the study. DISCUSSION: rTMS has obtained grade A evidence in treating patients with several central nervous system diseases, and there has been some evidence showing partial improvement on level of consciousness in DoC patients. However, the effectiveness of rTMS in DoC is only 30~36%, mostly due to the non-specific target selection. In this protocol, we present a double-blind crossover randomized sham-controlled trial based on the individualized-targeted selection strategy that aims to study the effectiveness of rTMS therapy for DoC, and the result may provide new insights to non-invasive brain stimulation. TRIAL REGISTRATION: ClinicalTrials.gov : NCT05187000. Registered on January 10, 2022.

Sensory impairments and subjective well-being status in middle-aged and older Chinese population: Cross-sectional and longitudinal analyses of a nationally representative survey.

Purpose: To investigate the impacts of sensory impairments (SIs) including single vision impairment (SVI), single hearing impairment (SHI) and dual sensory impairment (DSI) on subjective wellbeing measurements including life expectancy (LE), life satisfaction (LS) and self-rated health (SRH) in middle-aged and older Chinese population. Methods: We obtained data from the China Health and Retirement Longitudinal Survey (CHARLS). In total, 9,293 Chinese middle-aged and older adults aging over 45 were included at baseline 2011 in this study, and 3,932 participants who accomplished all 4 interviews from 2011 to 2018 were adapted for longitudinal analyses. Sensory status and subjective wellbeing measurements were collected. Other covariates included socio-demographic characteristics, medical condition and lifestyle-related factors. The impacts of baseline sensory status on LE, LS and SRH were assessed using univariate and multivariate logistic regression analyses. A linear regression analysis with generalized estimating equations (GEE) was used to assess the association between time-varying sensory statuses with LE, LS and SRH over 8 years after being adjusted with multi-confounding factors. Results: Participants with SIs had significantly lower level of LE, LS, and SRH, compared to those who were free of SI. All kinds of SIs were significantly associated with LE, LS, and SRH according to cross-sectional data. The correlations between SIs and LE or SRH over 8 years were also noticed. However, only SHI and DSI were found to be significantly associated with LS according to longitudinal data (all p values < 0.05). Conclusion: Sensory impairments had explicitly detrimental effects on subjective wellbeing status over time among middle-aged and older Chinese population.

An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping.

Genetic sharing is extensively observed for autoimmune diseases, but the causal variants and their underlying molecular mechanisms remain largely unknown. Through systematic investigation of autoimmune disease pleiotropic loci, we found most of these shared genetic effects are transmitted from regulatory code. We used an evidence-based strategy to functionally prioritize causal pleiotropic variants and identify their target genes. A top-ranked pleiotropic variant, rs4728142, yielded many lines of evidence as being causal. Mechanistically, the rs4728142-containing region interacts with the IRF5 alternative promoter in an allele-specific manner and orchestrates its upstream enhancer to regulate IRF5 alternative promoter usage through chromatin looping. A putative structural regulator, ZBTB3, mediates the allele-specific loop to promote IRF5-short transcript expression at the rs4728142 risk allele, resulting in IRF5 overactivation and M1 macrophage polarization. Together, our findings establish a causal mechanism between the regulatory variant and fine-scale molecular phenotype underlying the dysfunction of pleiotropic genes in human autoimmunity.

Why Employees Experience Burnout: An Explanation of Illegitimate Tasks.

Among the many workplace stressors, a new type of stressor has been identified: illegitimate tasks. This newly identified type of stressor refers to work tasks that do not meet employee role expectations and constitute a violation of professional identity. To investigate illegitimate tasks' mediating mechanisms and boundary conditions on job burnout, we examined a cross-level first-stage moderated mediation model with the collective climate as a moderator and psychological entitlement as a mediator. Grounded in the job demands-resources model (JD-R) and justice theory, the current study uniquely posits that illegitimate tasks can lead to burnout by way of psychological entitlement; however, this effect is less where collective climate is higher. Data were collected from 459 employees on 89 teams at enterprises in China. The results of the analysis, using HLM, MPLUS and SPSS revealed that illegitimate tasks stimulated employees' psychological entitlement and led to job burnout. While employees' psychological entitlement played a partially mediating role between illegitimate tasks and job burnout, a collective climate could weaken the stimulating effect of illegitimate tasks on employees' psychological entitlement and then negatively affect the mediating effect of psychological entitlement between illegitimate tasks and burnout. The study reveals the antecedents of burnout from the perspective of job tasks and psychological entitlement, offers practical insight into the mechanism of illegitimate tasks on employee job burnout and recommends that organizations develop a collective climate to reduce employees' psychological entitlement and job burnout for steady development of the enterprise.

Electronic skin based on cellulose/KCl/sorbitol organohydrogel.

With the increasing interests in the fields of wearable devices, it is essential yet also challenging to develop electronic skin with customized functionalities, especially for harsh conditions. Herein, by using KCl as both anti-solvent for cellulose regeneration and ionic charge carrier in the cellulose gel network, cellulose/KCl/sorbitol organohydrogel (CKS) combining transparency (over 95% at 550 nm), stretchability (235%), high conductivity (3.88 S/m), and low temperature tolerance (-51.8 °C) was prepared. The CKS based electronic skin achieved simultaneous monitoring of object contact-separation/pressure, stretching/bending and thermal variation, with excellent reliability and stability even in harsh conditions, resembling the human skin with multiply functions. The CKS based electronic skin as efficient human-machine interface was also demonstrated. Furthermore, the CKS based triboelectric nanogenerator delivered a power density of 991 mW/m2, potential as mechanical energy harvesters for wearable devices. We believe the present work will inspire the development of cellulose based skin-like materials and contribute to the comprehensive utilization of naturel polymer in the field of smart devices.

High-performance triboelectric nanogenerator based on chitin for mechanical-energy harvesting and self-powered sensing.

Environment issues and energy crisis call for eco-friendly, biodegradable and low-cost natural materials for the extensive application of distributed energy harvesting triboelectric nanogenerators (TENGs) and multi-functional self-powered sensors. Here, flexible, robust and transparent chitin films fabricated via non-freezing dissolution approach in KOH/urea were used as tribopositive material to assemble TENGs, which served as outstanding mechanical energy harvesters and multi-functional self-powered sensors. The tensile strength and elongation at break of the chitin film reached 84.7 MPa and 14.5%, better than most existing biodegradable-based films. The chitin-based TENG (CF-TENG) achieved open-circuit voltage up to 182.4 V, short-circuit current of 4.8 µA and maximum power density over 1.25 W m-2. Furthermore, the CF-TENG can be utilized as tactile sensors for handwriting recognition and health monitoring of subtle pressures, as well as non-contact sensation, exhibiting great potential as self-powered sensors and human-machine interfaces.

Reduced Peripheral Nerve Conduction Velocity is Associated with Alzheimer's Disease: A Cross-Sectional Study from China.

PURPOSE: Elderly individuals with degenerative diseases of the central nervous system are more likely to develop peripheral neuropathy; however, research is limited as to whether the decline in peripheral nerve conduction can be used as a biomarker of Alzheimer's disease (AD). PATIENTS AND METHODS: This study enrolled 74 patients with mild cognitive impairment (MCI), 21 with AD, and 82 healthy elderly individuals. All participants underwent a peripheral nerve conduction and neuropsychological evaluation. Nicolet EDX was used to assess peripheral nerve conduction in the limbs and comparisons were made between the three cognitive groups. Furthermore, the relationship between peripheral nerve conduction and cognitive function was investigated. RESULTS: A ladder-shaped difference was found in the median (p < 0.001) and common peroneal (p < 0.001) motor nerve velocity, with the control group > MCI group > AD group, even after controlling for variables. The median motor nerve amplitude in the AD group was lower than that in the control group (P = 0.017). After controlling for age, sex, education, and height, the median motor nerve velocity was positively correlated with the Montreal Cognitive Assessment (r = 0.196, p = 0.015), and the common peroneal motor nerve velocity was positively correlated with verbal fluency task-idioms (r = 0.184, p = 0.026). The median (AUC: 0.777, p < 0.001) and common peroneal motor nerve velocities (AUC: 0.862; p < 0.001) were significantly associated with the diagnosis of AD. The accuracy rate of these two motor nerve velocities to predict AD was 51.5%. CONCLUSION: Our study found that peripheral motor nerve velocity may correlate with early cognitive impairment in AD. However, the accuracy of different cognitive classifications and the value of early diagnosis are not ideal when peripheral motor nerve velocity is used alone. Whether peripheral nerve function can be used as a marker for early diagnosis of AD needs further clarification but provides a new possibility for the future of biomarker research.

Inhibition of cGAS in Paraventricular Nucleus Attenuates Hypertensive Heart Injury Via Regulating Microglial Autophagy.

Neuroinflammation in the cardiovascular center plays a critical role in the progression of hypertensive heart disease. And microglial autophagy is involved in the regulation of neuroinflammation. Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, senses mitochondrial DNA (mtDNA) and regulates autophagy. The detailed mechanisms of central cGAS affects neuroinflammatory response in hypertensive heart disease via regulating autophagy remain unknown. Angiotensin II (Ang II, 1.5 mg·kg-1·12 h-1, 2 weeks) was intraperitoneally injected to induce hypertension in mice. The cGAS-STING pathway was activated in the paraventricular nucleus (PVN) of Ang II-induced hypertensive mice. The contractile dysfunction of heart was alleviated in Ang II-induced hypertensive cGAS-/- mice. To observe the central effects of cGAS on regulating hypertensive heart disease, the RU.521 (a cGAS inhibitor) was intracisternally infused in hypertensive mice. Intracisternal infusion of the RU.521-alleviated myocardial interstitial fibrosis, cardiomyocyte hypertrophy, and the contractile dysfunction in Ang II-induced hypertensive mice. Intracisternal infusion of RU.521 attenuated the microglial activation, neuroinflammation, sympathetic/parasympathetic activity ratio, and lowered blood pressure. The autophagic flux in the PVN cells was blocked, while intracisternal infusion of RU.521 alleviated this effect in the Ang II-induced hypertensive mice. In vitro, it was found that cGAS-STING activation-induced autophagic flux blockage, while when the impaired autophagic flux was facilitated by rapamycin, an autophagy inducer, the microglial M1 polarization was decreased correspondingly. In conclusion, cGAS induces the inflammatory phenotype of microglia via impairing autophagic flux, thereby participating in neuroinflammation, which leads to sympathetic overactivation in hypertension and further caused hypertensive myocardial injury.