Ophiocordyceps sinensis preparations combined with the renin-angiotensin system inhibitor for diabetic kidney disease treatment: an umbrella review of systematic reviews and network meta-analysis.

Aims: This study aimed to synthesize the evidence of the comparative effectiveness and safety of Ophiocordyceps sinensis (OS) preparations combined with renin-angiotensin system inhibitors (RASi) for diabetic kidney disease (DKD). Methods: Eight databases were searched from their inception to May 2023. Systematic reviews (SRs) of OS preparations combined with RASi for DKD were identified. Randomized controlled trials (RCTs) from the included SRs and additional searching were performed for data pooling. Cochrane risk-of-bias 2 (RoB 2) tool and AMSTAR 2 were used to evaluate the methodological quality of RCTs and SRs, respectively. A Bayesian network meta-analysis was performed to compare the add-on effect and safety of OS preparations for DKD. The certainty of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: Fourteen SRs were included, whose methodological quality was assessed as high (1/14) or critically low (13/14). After combining additional searching, 157 RCTs were included, involving 13,143 participants. The quality of the RCTs showed some concerns (155/157) or high risk (2/157). Jinshuibao capsules and tablets, Bailing capsules and tablets, and Zhiling capsules were evaluated. Compared to RASi, adding either of the OS capsular preparations resulted in a decreased 24-h urinary total protein levels. OS preparations ranked differently in each outcome. Jinshuibao capsules plus RASi were beneficial in reducing urinary protein, serum creatinine, serum urea nitrogen, and blood glucose levels, with moderate-certainty evidence. No serious adverse events were observed after adding OS to RASi. Conclusion: Combining OS capsular preparations with RASi appeared to be associated with decreased urinary total protein levels in DKD patients. Further high-quality studies are needed to confirm. Systematic Review Registration: INPASY202350066.

Low neutralization of SARS-CoV-2 Omicron BA.5.2.48 and XBB.1 sub-variants in response to breakthrough infection by booster.

To assess the levels of and neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its mutants in serum samples from patients with breakthrough infection. Sixty-four patients with breakthrough infections were recruited for this cross-sectional study. All samples were used to neutralizing antibodies (nAbs) against SARS-CoV-2 and its mutants using a focused reduction neutralization assay. A total of 512 serum samples were obtained from unvaccinated patients who received one dose of vaccine (n = 12), received two doses of vaccine (n = 15), and received three doses of vaccine (n = 37). The geometric mean titer (GMT) of neutralizing antibodies against the Omicron subvariant was significantly lower (GMT 66.8 and 56.1) compared to the original strain, regardless of whether two or three doses of vaccine were administered. This result highlights that sera from breakthrough infections induce broad neutralization, but Omicron XBB.1.16 exhibits high immune evasion potential.

Guanylate-binding protein 1 inhibits inflammatory factors produced by H5N1 virus through Its GTPase activity.

The combination of inflammatory factors resulting from an influenza A virus infection is one of the main causes of death in host animals. Studies have shown that guinea pig guanosine monophosphate binding protein 1 (guanylate-binding protein 1, gGBP1) can downregulate cytokine production induced by the influenza virus. Therefore, exploring the innate immune defense mechanism of GBP1 in the process of H5N1 influenza virus infection has important implications for understanding the pathogenic mechanism, disease prevention, and the control of influenza A virus infections. We found that, in addition to inhibiting the early replication of influenza virus, gGBP1 also inhibited the production of CCL2 and CXCL10 cytokines induced by the influenza virus as well as the proliferation of mononuclear macrophages induced by these cytokines. These findings further confirmed that gGBP1 inhibited the production of cytokines through its GTPase activity and cell proliferation through its C-terminal α-helix structure. This study revealed the effect of gGBP1 on the production of cellular inflammatory factors during influenza virus infection and determined the key amino acid residues that assist in the inhibitory processes mediated by gGBP1.

Inducible Fgf13 ablation alleviates cardiac fibrosis via regulation of microtubule stability.

Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, boasts significant potential for therapeutic intervention in cardiovascular dysfunctions. However, its impact on regulating fibrosis remains unexplored. This study aims to elucidate the role and mechanism of FGF13 on cardiac fibrosis. Here, we show that following transverse aortic constriction (TAC) surgery, interstitial fibrosis and collagen content increase in mice, along with reduced ejection fraction and fractional shortening, augmented heart mass. However, following Fgf13 deletion, interstitial fibrosis is decreased, ejection fraction and fractional shortening are increased, and heart mass is decreased, compared with those in the TAC group. Mechanistically, incubation of cardiac fibroblasts with transforming growth factor ß (TGFß) increases the expressions of types I and III collagen proteins, as well as α-smooth muscle actin (α-SMA) proteins, and enhances fibroblast proliferation and migration. In the absence of Fgf13, the expressions of these proteins are decreased, and fibroblast proliferation and migration are suppressed, compared with those in the TGFß-stimulated group. Overexpression of FGF13, but not FGF13 mutants defective in microtubule binding and stabilization, rescues the decrease in collagen and α-SMA protein and weakens the proliferation and migration function of the Fgf13 knockdown group. Furthermore, Fgf13 knockdown decreases ROCK protein expression via microtubule disruption. Collectively, cardiac Fgf13 knockdown protects the heart from fibrosis in response to haemodynamic stress by modulating microtubule stabilization and ROCK signaling pathway.

A prospective randomized controlled clinical trial investigating the efficacy of low-dose olanzapine in preventing nausea and vomiting associated with oxaliplatin-based and irinotecan-based chemotherapy.

OBJECTIVE: The aim of this study is to assess the clinical efficacy of a 5 mg dosage of olanzapine in preventing chemotherapy-induced nausea and vomiting (CINV) associated with moderately emetogenic chemotherapy (MEC) among female patients diagnosed with gastrointestinal tract tumors. METHODS: Patients undergoing the oxaliplatin/irinotecan chemotherapy regimen were enrolled in this prospective controlled study. The olanzapine group received a 5 mg dosage of olanzapine along with palonosetron and dexamethasone, while the control group received a standard two-combination regimen consisting of dexamethasone and palonosetron. The primary endpoints included the total protection (TP) rates for the entire age group and the subgroup aged 60 years and above. Secondary endpoints encompassed the total protection rates during the acute and delayed phases within the two age brackets, as well as the total control (TC) rates and complete remission (CR) rates across all three phases (total, acute, and delayed). Additionally, the study involved the assessment of quality of life and the collection of adverse events associated with the interventions. RESULTS: 1) Regarding the primary endpoint, the total phase TP rates within both the entire age group and the age group exceeding 60 years demonstrated superiority in the olanzapine group when compared to the control group (66.7% vs 37.25%, P = 0.003; 68.8% vs 44.4%, P = 0.044). 2) In terms of secondary endpoints, the olanzapine group exhibited superior acute phase TP rates in both age brackets when compared to the control group (P < 0.05). The olanzapine group also demonstrated higher delayed-phase TP rates, TC rates across all three phases, and CR rates within the two age brackets, although the differences were not statistically significant (P > 0.05). Furthermore, the quality of life in the olanzapine group surpassed that of the control group for both age brackets (P < 0.05), characterized by enhanced appetite and a higher incidence of drowsiness in the patients treated with olanzapine when compared to those in the control group (P < 0.05). CONCLUSION: Olanzapine can enhance CINV induced by MEC regimen in female patients across all age groups, including the elderly, and therefore improve the quality of life for these patients. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/index.html , identifier: ChiCTR20000368269, 25/08/2020.

Dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer.

Objectives: In this study, we compared the dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer. Furthermore, we investigated the potential impact of these changes on the occurrence of toxic side effects. Methods: Patients with gastric cancer who received adjuvant or first-line XELOX/SOX chemotherapy between January 2020 and June 2023 were enrolled. The Brief Conghua Scale was used to assess energy intake, and nutritional management was carried out with reference to the Chinese Guidelines for Nutritional Therapy of Cancer 2020. The NRS 2002 Nutritional Risk Screening Scale, PG-SGA scale, bioelectrical impedance analysis, and dynamic changes in lumbar 3 vertebral skeletal muscle index were compared between baseline and post-chemotherapy in the study. The neutropenia was evaluated using the Common Terminology Criteria for Adverse Events V.5.0, developed by the National Institutes of Health. Results: Dynamic follow-up was completed in 39 cases, with a mean follow-up time of 117.62 ± 43.38 days. The incidence of sarcopenia increased significantly after chemotherapy, escalating from 46.2% to 51.3%. After chemotherapy, the mean L3SMI decreased from 36.00 cm2/m2 to 34.99 cm2/m2. Furthermore, when compared to pre-chemotherapy values, the body composition indexes body mass index (BMI), SL3, fat mass free index (FFMI), lean body mass (LBM), and body surface area (BSA) were significantly reduced after chemotherapy. Regardless of baseline or post-chemotherapy status, the incidence of grade ≥ 3 neutropenia was significantly higher in the sarcopenia group than in the non-sarcopenia group. Furthermore, when the skeletal muscle index decreased during chemotherapy, the incidence of grade ≥ 3 neutropenia was significantly higher in both the sarcopenia and non-sarcopenia groups compared to baseline. When the incidence of grade ≥ 3 neutropenia in the post-chemotherapy sarcopenia group was compared to baseline status, the increase was significantly higher in the sarcopenia group than in the maintenance/increase group. Conclusions: Skeletal muscle mass decreased progressively during XELOX/SOX chemotherapy in gastric cancer patients, followed by a higher incidence of grade ≥ 3 neutropenia.

Autophagy in hepatic progenitor cells modulates exosomal miRNAs to inhibit liver fibrosis in schistosomiasis.

Schistosoma infection is one of the major causes of liver fibrosis. Emerging roles of hepatic progenitor cells (HPCs) in the pathogenesis of liver fibrosis have been identified. Nevertheless, the precise mechanism underlying the role of HPCs in liver fibrosis in schistosomiasis remains unclear. This study examined how autophagy in HPCs affects schistosomiasis-induced liver fibrosis by modulating exosomal miRNAs. The activation of HPCs was verified by immunohistochemistry (IHC) and immunofluorescence (IF) staining in fibrotic liver from patients and mice with Schistosoma japonicum infection. By coculturing HPCs with hepatic stellate cells (HSCs) and assessing the autophagy level in HPCs by proteomic analysis and in vitro phenotypic assays, we found that impaired autophagy degradation in these activated HPCs was mediated by lysosomal dysfunction. Blocking autophagy by the autophagy inhibitor chloroquine (CQ) significantly diminished liver fibrosis and granuloma formation in S. japonicum-infected mice. HPC-secreted extracellular vehicles (EVs) were further isolated and studied by miRNA sequencing. miR-1306-3p, miR-493-3p, and miR-34a-5p were identified, and their distribution into EVs was inhibited due to impaired autophagy in HPCs, which contributed to suppressing HSC activation. In conclusion, we showed that the altered autophagy process upon HPC activation may prevent liver fibrosis by modulating exosomal miRNA release and inhibiting HSC activation in schistosomiasis. Targeting the autophagy degradation process may be a therapeutic strategy for liver fibrosis during Schistosoma infection.

Modulation of Gut Microbial Community and Metabolism by Bacillus licheniformis HD173 Promotes the Growth of Nursery Piglets Model.

Maintaining the balance and stability of the gut microbiota is crucial for the gut health and growth development of humans and animals. Bacillus licheniformis (B. licheniformis) has been reported to be beneficial to the gut health of humans and animals, whereas the probiotic effects of a new strain, B. licheniformis HD173, remain uncertain. In this study, nursery piglets were utilized as animal models to investigate the extensive impact of B. licheniformis HD173 on gut microbiota, metabolites, and host health. The major findings were that this probiotic enhanced the growth performance and improved the health status of the nursery piglets. Specifically, it reduced the level of pro-inflammatory cytokines IL-1ß and TNF-α in the serum while increasing the level of IL-10 and SOD. In the gut, B. licheniformis HD173 reduced the abundance of pathogenic bacteria such as Mycoplasma, Vibrio, and Vibrio metschnikovii, while it increased the abundance of butyrate-producing bacteria, including Oscillospira, Coprococcus, and Roseburia faecis, leading to an enhanced production of butyric acid. Furthermore, B. licheniformis HD173 effectively improved the gut metabolic status, enabling the gut microbiota to provide the host with stronger metabolic abilities for nutrients. In summary, these findings provide scientific evidence for the utilization of B. licheniformis HD173 in the development and production of probiotic products for maintaining gut health in humans and animals.

Piezocatalytically-induced controllable mineralization scaffold with bone-like microenvironment to achieve endogenous bone regeneration.

Orderly hierarchical structure with balanced mechanical, chemical, and electrical properties is the basis of the natural bone microenvironment. Inspired by nature, we developed a piezocatalytically-induced controlled mineralization strategy using piezoelectric polymer poly-L-lactic acid (PLLA) fibers with ordered micro-nano structures to prepare biomimetic tissue engineering scaffolds with a bone-like microenvironment (pcm-PLLA), in which PLLA-mediated piezoelectric catalysis promoted the in-situ polymerization of dopamine and subsequently regulated the controllable growth of hydroxyapatite crystals on the fiber surface. PLLA fibers, as analogs of mineralized collagen fibers, were arranged in an oriented manner, and ultimately formed a bone-like interconnected pore structure; in addition, they also provided bone-like piezoelectric properties. The uniformly sized HA nanocrystals formed by controlled mineralization provided a bone-like mechanical strength and chemical environment. The pcm-PLLA scaffold could rapidly recruit endogenous stem cells, and promote their osteogenic differentiation by activating cell membrane calcium channels and PI3K signaling pathways through ultrasound-responsive piezoelectric signals. In addition, the scaffold also provided a suitable microenvironment to promote macrophage M2 polarization and angiogenesis, thereby enhancing bone regeneration in skull defects of rats. The proposed piezocatalytically-induced controllable mineralization strategy provides a new idea for the development of tissue engineering scaffolds that can be implemented for multimodal physical stimulation therapy.

Diabetes and osteoporosis: a two-sample mendelian randomization study.

BACKGROUND: The effects on bone mineral density (BMD)/fracture between type 1 (T1D) and type 2 (T2D) diabetes are unknown. Therefore, we aimed to investigate the causal relationship between the two types of diabetes and BMD/fracture using a Mendelian randomization (MR) design. METHODS: A two-sample MR study was conducted to examine the causal relationship between diabetes and BMD/fracture, with three phenotypes (T1D, T2D, and glycosylated hemoglobin [HbA1c]) of diabetes as exposures and five phenotypes (femoral neck BMD [FN-BMD], lumbar spine BMD [LS-BMD], heel-BMD, total body BMD [TB-BMD], and fracture) as outcomes, combining MR-Egger, weighted median, simple mode, and inverse variance weighted (IVW) sensitivity assessments. Additionally, horizontal pleiotropy was evaluated and corrected using the residual sum and outlier approaches. RESULTS: The IVW method showed that genetically predicted T1D was negatively associated with TB-BMD (ß = -0.018, 95% CI: -0.030, -0.006), while T2D was positively associated with FN-BMD (ß = 0.033, 95% CI: 0.003, 0.062), heel-BMD (ß = 0.018, 95% CI: 0.006, 0.031), and TB-BMD (ß = 0.050, 95% CI: 0.022, 0.079). Further, HbA1c was not associated with the five outcomes (ß ranged from - 0.012 to 0.075). CONCLUSIONS: Our results showed that T1D and T2D have different effects on BMD at the genetic level. BMD decreased in patients with T1D and increased in those with T2D. These findings highlight the complex interplay between diabetes and bone health, suggesting potential age-specific effects and genetic influences. To better understand the mechanisms of bone metabolism in patients with diabetes, further longitudinal studies are required to explain BMD changes in different types of diabetes.

Microfluidic sensors for the detection of emerging contaminants in water: A review.

In recent years, numerous emerging contaminants have been identified in surface water, groundwater, and drinking water. Developing novel sensing methods for detecting diverse emerging pollutants in water is urgently needed, as even at low concentrations, these pollutants can pose a serious threat to human health and environmental safety. Traditional testing methods are based on laboratory equipment, which is highly sensitive but complex to operate, costly, and not suitable for on-site monitoring. Microfluidic sensors offer several benefits, including rapid evaluation, minimal sample usage, accurate liquid manipulation, compact size, automation, and in-situ detection capabilities. They provide promising and efficient analytical tools for high-performance sensing platforms in monitoring emerging contaminants in water. In this paper, recent research advances in microfluidic sensors for the detection of emerging contaminants in water are reviewed. Initially, a concise overview is provided about the various substrate materials, corresponding microfabrication techniques, different driving forces, and commonly used detection techniques for microfluidic devices. Subsequently, a comprehensive analysis is conducted on microfluidic detection methods for endocrine-disrupting chemicals, pharmaceuticals and personal care products, microplastics, and perfluorinated compounds. Finally, the prospects and future challenges of microfluidic sensors in this field are discussed.

Phosphorus-doped nickel cobalt oxide (NiCo2O4) wrapped in 3D hierarchical hollow N-doped carbon nanoflowers as highly efficient bifunctional electrocatalysts for overall water splitting.

Properly design and fabricate capable electrocatalysts with 3D hierarchical hollow framework to realize cost-effective and efficacious overall water splitting (OWS) are particularly meaningful for the large-scale arrangement of pivotal energy technology. In this study, P-doped NiCo2O4 nanoparticles encapsulated in N-doped carbon hierarchical hollow nanoflowers (P-NiCo2O4@NCHHNFs) were constructed using the hydrothermal-pyrolysis-phosphorization approach. This fascinating architecture can not merely serve as a conductive pathway for electron transfer, but at the same time effectively inhibited the aggregation and corrosion of the NiCo2O4 nanoparticles. Additionally, the P doping not only regulates electronic structure configuration to boost the intrinsic activity of the catalyst, but also enhance electrochemical surface areas to reveal more accessible active sites. Attributing to these characteristics, the as-prepared P-NiCo2O4@NCHHNFs exhibit preeminent electrocatalytic performance with low overpotentials of 283 mV and 162 mV for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) (at 10 mA cm-2), respectively. Specifically, by using the P-NiCo2O4@NCHHNFs as bifunctional catalysts, a low potential of 1.56 V (at 10 mA cm-2) is sufficient to drive overall water splitting with splendid durability. This study proposed an innovative strategy for the conceiving and fabricating high-performance catalysts via heteroatom-doping.

Molecular Regulation of Porcine Skeletal Muscle Development: Insights from Research on CDC23 Expression and Function.

Cell division cycle 23 (CDC23) is a component of the tetratricopeptide repeat (TPR) subunit in the anaphase-promoting complex or cyclosome (APC/C) complex, which participates in the regulation of mitosis in eukaryotes. However, the regulatory model and mechanism by which the CDC23 gene regulates muscle production in pigs are largely unknown. In this study, we investigated the expression of CDC23 in pigs, and the results indicated that CDC23 is widely expressed in various tissues and organs. In vitro cell experiments have demonstrated that CDC23 promotes the proliferation of myoblasts, as well as significantly positively regulating the differentiation of skeletal muscle satellite cells. In addition, Gene Set Enrichment Analysis (GSEA) revealed a significant downregulation of the cell cycle pathway during the differentiation process of skeletal muscle satellite cells. The protein-protein interaction (PPI) network showed a high degree of interaction between genes related to the cell cycle pathway and CDC23. Subsequently, in differentiated myocytes induced after overexpression of CDC23, the level of CDC23 exhibited a significant negative correlation with the expression of key factors in the cell cycle pathway, suggesting that CDC23 may be involved in the inhibition of the cell cycle signaling pathway in order to promote the differentiation process. In summary, we preliminarily determined the function of CDC23 with the aim of providing new insights into molecular regulation during porcine skeletal muscle development.

Ultra-Strong Janus Covalent Organic Framework Membrane with Smart Response to Organic Vapor.

Vapor-driven smart Janus materials have made significant advancements in intelligent monitoring, control, and interaction, etc. Nevertheless, the development of ultrafast response single-layer Janus membrane, along with a deep exploration of the smart response mechanisms, remains a long-term endeavor. Here, the successful synthesis of a high-crystallinity single-layer Covalent organic framework (COF) Janus membrane is reported by morphology control. This kind of membrane displays superior mechanical properties and specific surface area, along with excellent responsiveness to CH2Cl2 vapor. The analysis of the underlying mechanisms reveals that the vapor-induced breathing effect of the COF and the stress mismatch of the Janus structure play a crucial role in its smart deformation performance. It is believed that this COF Janus membrane holds promise for complex tasks in various fields.

Dynamic Insights into the Growth Mechanisms of 2D Covalent Organic Frameworks on Graphene Surfaces.

Producing high-quality two-dimensional (2D) covalent organic frameworks (COFs) is crucial for industrial applications. However, this remains significantly challenging with current synthetic techniques. A deep understanding of the intermolecular interactions, reaction temperature, and oligomers is essential to facilitate the growth of highly crystalline COF films. Herein, molecular dynamics simulations were employed to explore the growth of 2D COFs from monomer assemblies on graphene. Our results showed that chain growth reactions dominated the COF surface growth and that van der Waals (vdW) interactions were important in enhancing the crystallinity through monomer preorganization. Moreover, appropriately tuning the reaction temperature improved the COF crystallinity and minimized the effects of amorphous oligomers. Additionally, the strength of the interface between the COF and the graphene substrate indicated that the adhesion force was proportional to the crystallinity of the COF. This work reveals the mechanisms for nucleation and growth of COFs on surfaces and provides theoretical guidance for fabricating high-quality 2D polymer-based crystalline nanomaterials.

Correction: Teng et al. Efficacy Assessment of Phage Therapy in Treating Staphylococcus aureus-Induced Mastitis in Mice. Viruses 2022, 14, 620.

In the original publication [...].

Disease-modifying therapy in progressive multiple sclerosis: a systematic review and network meta-analysis of randomized controlled trials.

Background: Currently, disease-modifying therapies (DMTs) for progressive multiple sclerosis (PMS) are widely used in clinical practice. At the same time, there are a variety of drug options for DMTs, but the effect of the drugs that can better relieve symptoms and improve the prognosis are still inconclusive. Objectives: This systematic review aimed to evaluate the efficacy and safety of DMTs for PMS and to identify the best among these drugs. Methods: MEDLINE, EMBASE, the Cochrane Library, and clinicaltrials.gov were systematically searched to identify relevant studies published before 30 January, 2023. We assessed the certainty of the evidence using the confidence in the network meta-analysis (CINeMA) framework. We estimated the summary risk ratio (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes with 95% credible intervals (CrIs). Results: We included 18 randomized controlled trials (RCTs) involving 9,234 patients in the study. DMT can effectively control the disease progression of MS. Among them, mitoxantrone, siponimod, and ocrelizumab are superior to other drug options in delaying disease progression (high certainty). Mitoxantrone was the best (with high certainty) for mitigating deterioration (progression of disability). Ocrelizumab performed best on the pre- and post-treatment Timed 25-Foot Walk test (T25FW; low certainty), as did all other agents (RR range: 1.12-1.05). In the 9-Hole Peg Test (9HPT), natalizumab performed the best (high certainty), as did all other agents (RR range: 1.59-1.09). In terms of imaging, IFN-beta-1b performed better on the new T2 hypointense lesion on contrast, before and after treatment (high certainty), while siponimod performed best on the change from baseline in the total volume of lesions on T2-weighted image contrast before and after treatment (high certainty), and sWASO had the highest area under the curve (SUCRA) value (100%). In terms of adverse events (AEs), rituximab (RR 1.01), and laquinimod (RR 1.02) were more effective than the placebo (high certainty). In terms of serious adverse events (SAEs), natalizumab (RR 1.09), and ocrelizumab (RR 1.07) were safer than placebo (high certainty). Conclusion: DMTs can effectively control disease progression and reduce disease deterioration during the treatment of PMS. Systematic review registration: https://inplasy.com/?s=202320071, identifier: 202320071.

Hypothesis Tests for Continuous Audiometric Threshold Data.

OBJECTIVES: Hypothesis tests for hearing threshold data may be challenging due to the special structure of the response variable, which consists of the measurements from the participant's two ears at multiple frequencies. The commonly-used methods may have inflated type I error rates for the global test that examines whether exposure-hearing threshold associations exist in at least one of the frequencies. We propose using both-ear methods, including all frequencies in the same model for hypothesis testing. DESIGN: We compared the both-ear method to commonly used single-ear methods, such as the worse-ear, better-ear, left/right-ear, average-ear methods, and both-ear methods that evaluate individual audiometric frequencies in separate models, through both theoretical consideration and a simulation study. Differences between the methods were illustrated using hypothesis tests for the associations between the Dietary Approaches to Stop Hypertension adherence score and 3-year change in hearing thresholds among participants in the Conservation of Hearing Study. RESULTS: We found that (1) in the absence of ear-level confounders, the better-ear, worse-ear and left/right-ear methods have less power for frequency-specific tests and for the global test; (2) in the presence of ear-level confounders, the better-ear and worse-ear methods are invalid, and the left/right-ear and average-ear methods have less power, with the power loss in the left/right-ear much greater than the average-ear method, for frequency-specific tests and for the global test; and (3) the both-ear method with separate analyses for individual frequencies is invalid for the global test. CONCLUSIONS: For hypothesis testing to evaluate whether there are significant associations between an exposure of interest and audiometric hearing threshold measurements, the both-ear method that includes all frequencies in the same model is the recommended analytic approach.

Recent advancements in hydrogels as novel tissue engineering scaffolds for dental pulp regeneration.

Although conventional root canal treatment offers an effective therapeutic solution, it negatively affects the viability of the affected tooth. In recent years, pulp regeneration technology has emerged as a novel method for treating irreversible pulpitis due to its ability to maintain tooth vitality. The successful implementation of this technique depends on scaffolds and transplantation of exogenous stem cells or recruitment of endogenous stem cells. Accordingly, the three-dimensional structure and viscoelastic characteristics of hydrogel scaffolds, which parallel those of the extracellular matrix, have generated considerable interest. Furthermore, hydrogels support the controlled release of regenerative drugs and to load a wide variety of bioactive molecules. By integrating antibacterial agents into the hydrogel matrix and stimulating an immune response, root canal disinfection can be significantly improved and the rate of pulp regeneration can be accelerated. This review aims to provide an overview of the clinical applications of hydrogels that have been reported in the last 5 years, and offer a comprehensive summary of the different approaches that have been utilized for the optimization of hydrogel scaffolds for pulp regeneration. Advancements and challenges in pulp regeneration using hydrogels treating aged teeth are discussed.