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Abstract Parkinson’s disease (PD) is a prevalent type of neurodegenerative disorder. AVE0991, a non-peptide analogue of Ang-(1–7), by which the progression of PD has been discovered to be ameliorated, but the specific mechanism whereby AVE0991 modulates the progression of PD re-mains unclear. The mice overexpressing human α-syn (A53T) were established to simulate PD pathology, and we also constructed an in vitro model of mouse dopaminergic neurons overexpressing hα-syn (A53T). The [18F] FDG-PET/CT method was employed to assess FDG uptake in human α-syn (A53T) overexpressing mice. Levels of lnc HOTAIRM1 and miR-223-3p were detected via qRT-PCR. Flow cytometry was deployed to assay cell apoptosis. Here, we found that AVE0991 improved behaviour disorders and decreased α-syn expression in the substantia nigra of mice with Parkinson’s disease. AVE0991 inhibited the apoptosis of dopaminergic neurons overexpressing hα-syn (A53T) via lncRNA HOTAIRM1. MiR-223-3p binds to HOTAIRM1 as a ceRNA and directly targets α-syn. Moreover, miR-223-3p level in peripheral blood was found negatively correlated with the α-syn. Our present study shows that the angiotensin-(1–7) analogue AVE0991 targeted at the HOTAIRM1/miR-223-3p axis to degrade α-synuclein in PD mice, and showed neuroprotection in vitro.

Abstract Background Contrast-induced acute kidney injury (CI-AKI) is manifested by a rapid decline in renal function occurring within 48–72 h in patients exposed to iodinated contrast media (CM). Although intravenous hydration is currently the effective method confirmed to prevent CI-AKI, it has several drawbacks. Some investigations have demonstrated the nephroprotective effects of vagus nerve stimulation (VNS) against kidney ischemia-reperfusion injury, but no direct research has investigated the use of VNS for treating CI-AKI. Additionally, most current VNS treatment applies invasive electrical stimulator implantation, which is largely limited by the complications. Our recent publications introduce the magnetic vagus nerve stimulation (mVNS) system pioneered and successfully used for the treatment of myocardial infarction. However, it remains uncertain whether mVNS can mitigate CI-AKI and its specific underlying mechanisms. Therefore, we herein evaluate the potential therapeutic effects of mVNS on CM-induced nephropathy in rats and explore the underlying mechanisms. Results mVNS treatment was found to significantly improve the damaged renal function, including the reduction of elevated serum creatinine (Scr), blood urea nitrogen (BUN), and urinary N-acetyl-β-D-glucosaminidase (NAG) with increased urine output. Pathologically, mVNS treatment alleviated the renal tissue structure injury, and suppressed kidney injury molecule-1 (KIM-1) expression and apoptosis in renal tubular epithelial cells. Mechanistically, increased circulating plasma exosomal miR-365-3p after mVNS treatment enhanced the autophagy and reduced CM-induced apoptosis in renal tubular epithelial cells by targeting Ras homolog enriched in brain (Rheb). Conclusions In summary, we demonstrated that mVNS can improve CI-AKI through enhanced autophagy and apoptosis inhibition, which depended on plasma exosomal miR-365-3p. Our findings highlight the therapeutic potential of mVNS for CI-AKI in clinical practice. However, further research is needed to determine the optimal stimulation parameters to achieve the best therapeutic effects. Graphical abstract

Abstract Background Aging negatively impacts tissue repair, particularly in skeletal muscle, where the regenerative capacity of muscle stem cells (MuSCs) diminishes with age. Although aerobic exercise is known to attenuate skeletal muscle atrophy, its specific impact on the regenerative and repair capacity of MuSCs remains unclear. Methods Mice underwent moderate‐intensity continuous training (MICT) from 9 months (aged + Ex‐9M) or 20 months (aged + Ex‐20M) to 25 months, with age‐matched (aged) and adult controls. Histological examinations and MuSC transplantation assays assessed aerobic exercise effects on MuSC function and muscle regeneration. CCN2/connective tissue growth factor modulation (overexpression and knockdown) in MuSCs and AICAR supplementation effects were explored. Results Aged mice displayed significantly reduced running duration (65.33 ± 4.32 vs. 161.9 ± 1.29 min, mean ± SD, P

Abstract BackgroundType 2 diabetes mellitus (T2DM) is a common health issue, with heart failure (HF) being a common and lethal long-term complication. Although insulin is widely used for the treatment of T2DM, evidence regarding the efficacy of insulin compared to noninsulin therapies on incident HF risk is missing among randomized controlled trials. Real-world evidence on insulin’s effect on long-term HF risk may supplement existing guidelines on the management of T2DM. ObjectiveThis study aimed to compare insulin therapy against other medications on HF risk among patients with T2DM using real-world data extracted from insurance claims. MethodsA retrospective, observational study was conducted based on insurance claims data from a single health care network. The study period was from January 1, 2016, to August 11, 2021. The cohort was defined as patients having a T2DM diagnosis code. The inclusion criteria were patients who had at least 1 record of a glycated hemoglobin laboratory test result; full insurance for at least 1 year (either commercial or Medicare Part D); and received glucose-lowering therapy belonging to 1 of the following groups: insulin, glucagon-like peptide 1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 inhibitors (DPP-4Is), or sodium-glucose cotransporter-2 inhibitors (SGLT2Is). The main outcome was the 5-year incident HF rate. Baseline covariates, including demographic characteristics, comorbidities, and laboratory test results, were adjusted to correct for confounding. ResultsAfter adjusting for a broad list of confounders, patients receiving insulin were found to be associated with an 11.8% (95% CI 11.0%‐12.7%), 12.0% (95% CI 11.5%‐12.4%), and 15.1% (95% CI 14.3%‐16.0%) higher 5-year HF rate compared to those using GLP-1 RAs, DPP-4Is, and SGLT2Is, respectively. Subgroup analysis showed that insulin’s effect of a higher HF rate was significant in the subgroup with high HF risk but not significant in the subgroup with low HF risk. ConclusionsThis study generated real-world evidence on the association of insulin therapy with a higher 5-year HF rate compared to GLP-1 RAs, DPP-4Is, and SGLT2Is based on insurance claims data. These findings also demonstrated the value of real-world data for comparative effectiveness studies to complement established guidelines. On the other hand, the study shares the common limitations of observational studies. Even though high-dimensional confounders are adjusted, remaining confounding may exist and induce bias in the analysis.

Abstract Background Porcine cysticercosis, a serious zoonotic parasitic disease, is caused by the larvae of Taenia solium and has been acknowledged by the World Organization for Animal Health. The current detection methods of Cysticercus cellulosae cannot meet the needs of large-scale and rapid detection in the field. We hypothesized that the immunofluorescence chromatography test strip (ICS) for detecting Cysticercus cellulosae, according to optimization of a series of reaction systems was conducted, and sensitivity, specificity, and stability testing, and was finally compared with ELISA. This method utilizes Eu3+-labeled time-resolved fluorescent microspheres (TRFM) coupled with TSOL18 antigen to detect TSOL18 antibodies in infected pig sera. Results ICS and autopsy have highly consistent diagnostic results (n = 133), as determined by Cohen’s κ analysis (κ = 0.925). And the results showed that the proposed ICS are high sensitivity (0.9459) with specificity (0.9792). The ICS was unable to detect positive samples of other parasites. It can be stored for at least six months at 4℃. Conclusions In summary, we established a TRFM-ICS method with higher sensitivity and specificity than indirect ELISA. Results obtained from serum samples can be read within 10 min, indicating a rapid, user-friendly test suitable for large-scale field detection.

Purpose: To construct optimal models for predicting the invasiveness and pathological subtypes of subsolid nodules (SSNs) based on CT radiomics and clinical features. Materials and Methods: This study was a retrospective study involving two centers. A total of 316 patients with 353 SSNs confirmed as atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) were included from January 2019 to February 2023. Models based on CT radiomics and clinical features were constructed for classification of AAH/AIS and MIA, MIA and IAC, as well as lepidic-predominant adenocarcinoma (LPA) and acinar-predominant adenocarcinoma (APA). Receiver operating characteristic (ROC) curve was used to evaluate the model performance. Finally, the nomograms based on the optimal models were established. Results: The nomogram based on the combined model (AAH/AIS versus MIA) consisting of lobulation, the GGN-vessel relationship, diameter, CT value, consolidation tumor ratio (CTR) and rad-score performed the best (AUC=0.841), while age, CT value, CTR and rad-score were the significant features for distinguishing MIA from IAC, the nomogram based on these features performed the best (AUC=0.878). There were no significant differences in clinical features between LPA and APA, while the radiomics model based on rad-score showed good performance for distinguishing LPA from APA (AUC=0.926). Conclusions: The nomograms based on radiomics and clinical features could predict the invasiveness of SSNs accurately. Moreover, radiomics models showed good performance in distinguishing LPA from APA.

Abstract Objective Most people with epilepsy (PWE) could live seizure‐free if treated with one or more antiseizure medications (ASMs). The World Health Organization (WHO) estimates that 75% of PWE in low‐resource settings lack adequate antiseizure treatment. Limited education surrounding epilepsy and the out‐of‐pocket costs of ASMs in particular pose barriers to managing epilepsy in resource‐poor, low‐income settings. The aim of this study is to implement and test a novel strategy to improve outcomes across the epilepsy care cascade marked by (1) retention in epilepsy care, (2) adherence to ASMs, and (3) seizure reduction, with the measured goal of seizure freedom. Methods A randomized, double‐blinded clinical trial will be performed, centered at the Ignace Deen Hospital in Conakry, Republic of Guinea, in Western Sub‐Saharan Africa. Two hundred people with clinically diagnosed epilepsy, ages 18 years and above, will receive education on epilepsy and then be randomized to (i) free ASMs versus (ii) conditional cash, conditioned upon return to the epilepsy clinic. Participants will be followed for 360 days with study visits every 90 days following enrollment. Significance We design a randomized trial for PWE in Guinea, a low‐resource setting with a high proportion of untreated PWE and a nearly completely privatized healthcare system. The trial includes a conditional cash transfer intervention, which has yet to be tested as a targeted means to improve outcomes for people with a chronic neurological disorder. The trial aims to provide an evidence base for the treatment of epilepsy in such settings. Plain Language Summary We present a clinical trial protocol for a randomized, blinded study of 200 people with epilepsy in the low‐resource African Republic of Guinea, providing an educational intervention (E), and then randomizing in a 1:1 allocation to either free antiseizure medication (m) or conditional cash (c2) for 360 days. Measured outcomes include (1) returning to outpatient epilepsy care, (2) adherence to antiseizure medications (ASMs), and (3) reducing the number of seizures. This study is an initial look at giving small amounts of cash for desired results (or “nudges”) for improving epilepsy outcomes in the sub‐Saharan African and brain disorder contexts.

Atherosclerosis is an autoimmune disease characterized by lipid imbalances and chronic inflammation within blood vessels, with limited preventive and treatment options currently available. In this study, a vaccine prepared with COL6A6 peptide (named the Pep_A6 vaccine) was administered to immunize Apoe−/− mice, and the immune mechanism of the Pep_A6 vaccine against atherosclerosis was first investigated. The results of arterial oil red O staining demonstrated that the Pep_A6 vaccine significantly reduced the atherosclerotic plaque area in Apoe−/− mice fed with a high-fat diet for 20 weeks. A flow cytometry analysis revealed that the Pep_A6 vaccine inhibited Th1 cell differentiation and increased the proportion of Treg cells. Furthermore, there was a significant increase in Ly6Clow monocytes observed in the vaccinated group. The ELISA results showed that the Pep_A6 vaccine induced a significant expression of Pep_A6-specific antibody IgG and IgG1 in mouse serum. Additionally, we found that the Pep_A6 vaccine significantly decreased serum LDL-C content and regulated the expression of genes related to liver lipid metabolism. Together, our findings suggest that the Pep_A6 vaccine alleviates atherosclerosis by inducing a positive immune response and regulating lipid metabolism, providing new insights into potential prevention strategies for atherosclerosis as an innovative vaccine.

Introduction:Exercise, health, and the gut microbiota (GM) are strongly correlated. Research indicates that professional athletes, especially ultra-marathon runners, have unique GM characteristics. However, more research has focused on elite athletes, with little attention given to amateur sports enthusiasts, especially those in the middle-aged population. Therefore, this study focuses on the impact of long-term running on the composition and potential functions of the GM in middle-aged individuals.Methods:We compared the GM of 25 middle-aged serious runnerswith 22 sedentary healthy controls who had minimal exercise habitsusing 16S rRNA gene sequencing. Additionally, we assessed dietary habits using a food frequency questionnaire.Results and Discussion:Statistical analysis indicates that there is no significant difference in dietary patterns between the control group and serious runners. Diversity analysis results indicate that there is no significant difference in α diversity between the two groups of GM, but there is a significant difference in β diversity. Analysis of the composition of GM reveals that Ruminococcus and Coprococcus are significantly enriched in serious runners, whereas Bacteroides, Lachnoclostridium, and Lachnospira are enriched in the control group. Differential analysis of functional pathway prediction results reveals significant differences in the functional metabolism levels of GM between serious runners and the control group. Further correlation analysis results indicate that this difference may be closely related to variations in GM. In conclusion, our results suggest that long-term exercise can lead to changes in the composition of the GM. These changes have the potential to impact the overall health of the individual by influencing metabolic regulation.

Abstract In response to the escalating global obesity crisis and its associated health and financial burdens, this paper presents a novel methodology for analyzing longitudinal weight loss data and assessing the effectiveness of financial incentives. Drawing from the Keep It Off trial—a three-arm randomized controlled study with 189 participants—we examined the potential impact of financial incentives on weight loss maintenance. Given that some participants choose not to weigh themselves because of small weight change or weight gains, which is a common phenomenon in many weight-loss studies, traditional methods, for example, the Generalized Estimating Equations (GEE) method tends to overestimate the effect size due to the assumption that data are missing completely at random. To address this challenge, we proposed a framework which can identify evidence of missing not at random and conduct bias correction using the estimating equation derived from pairwise composite likelihood. By analyzing the Keep It Off data, we found that the data in this trial are most likely characterized by non-random missingness. Notably, we also found that the enrollment time (i.e., duration time) would be positively associated with the weight loss maintenance after adjusting for the baseline participant characteristics (e.g., age, sex). Moreover, the lottery-based intervention was found to be more effective in weight loss maintenance compared with the direct payment intervention, though the difference was non-statistically significant. This framework's significance extends beyond weight loss research, offering a semi-parametric approach to assess missing data mechanisms and robustly explore associations between exposures (e.g., financial incentives) and key outcomes (e.g., weight loss maintenance). In essence, the proposed methodology provides a powerful toolkit for analyzing real-world longitudinal data, particularly in scenarios with data missing not at random, enriching comprehension of intricate dataset dynamics.

Abstract Oligodendrocyte progenitor cells (OPCs) play pivotal roles in myelin formation and phagocytosis, communicating with neighboring cells and contributing to the integrity of the blood–brain barrier (BBB). However, under the pathological circumstances of Alzheimer’s disease (AD), the brain’s microenvironment undergoes detrimental changes that significantly impact OPCs and their functions. Starting with OPC functions, we delve into the transformation of OPCs to myelin-producing oligodendrocytes, the intricate signaling interactions with other cells in the central nervous system (CNS), and the fascinating process of phagocytosis, which influences the function of OPCs and affects CNS homeostasis. Moreover, we discuss the essential role of OPCs in BBB formation and highlight the critical contribution of OPCs in forming CNS-protective barriers. In the context of AD, the deterioration of the local microenvironment in the brain is discussed, mainly focusing on neuroinflammation, oxidative stress, and the accumulation of toxic proteins. The detrimental changes disturb the delicate balance in the brain, impacting the regenerative capacity of OPCs and compromising myelin integrity. Under pathological conditions, OPCs experience significant alterations in migration and proliferation, leading to impaired differentiation and a reduced ability to produce mature oligodendrocytes. Moreover, myelin degeneration and formation become increasingly active in AD, contributing to progressive neurodegeneration. Finally, we summarize the current therapeutic approaches targeting OPCs in AD. Strategies to revitalize OPC senescence, modulate signaling pathways to enhance OPC differentiation, and explore other potential therapeutic avenues are promising in alleviating the impact of AD on OPCs and CNS function. In conclusion, this review highlights the indispensable role of OPCs in CNS function and their involvement in the pathogenesis of AD. The intricate interplay between OPCs and the AD brain microenvironment underscores the complexity of neurodegenerative diseases. Insights from studying OPCs under pathological conditions provide a foundation for innovative therapeutic strategies targeting OPCs and fostering neurodegeneration. Future research will advance our understanding and management of neurodegenerative diseases, ultimately offering hope for effective treatments and improved quality of life for those affected by AD and related disorders.

Deep-water oil and gas is currently the hot spot and difficulty of global oil and gas exploration, and the complex flow process inside the turbidite channels of deep-water canyons makes it difficult to characterize reservoir structures, identify barriers and interlayers and clarify the spatial distribution laws of reservoirs, which restricts the development of deep-water oil and gas. Taking the Central Canyon of the Qiongdongnan Basin as an example, this paper identifies and characterizes the barriers and interlayers of composite channel scale by means of seismic sedimentology, based on three-dimensional seismic and core data. Then, based on the turbidite filling process, barriers and interlayers are classified, and their genesis and control factors are analyzed. Finally, a development model of deep-water barriers and interlayers is established based on the quantitative analysis of sediment transportation system parameters. And the following research results are obtained. First, based on sedimentary genesis, barriers and interlayers are classified into four types, namely mudstone interlayers of lateral (aggradational) turbidite channel genesis (type A), mudstone interlayers of fine-grained turbidite channel genesis (type B), barriers of hemipelagic deep-water sediment genesis (type C), and calcareous petrophysical interlayers (type D). Second, based on the filling stage, barriers and interlayers are divided into four combination sequences, i.e., the initial canyon formation stage with strong sediment supply conditions (type A + type C and type B+ type C), the initial canyon formation stage with weak sediment supply conditions (type B + type C), the stable canyon development/late reworking stage with strong sediment supply conditions (types A + type D), and the stable canyon development/late reworking stage with weak sediment supply conditions (type D). Third, the development types and combination sequences of barriers and interlayers are controlled by the change of sediment transportation volume and terrain slope in the canyon. In the initial canyon formation stage, there is sufficient space for the development of turbidite, and the development of thin barriers and interlayers is controlled by sediment dischage volume, while the development of thick barriers and interlayers is controlled by terrain slope change. In the stable canyon development/late reworking stage, turbidite undergoes superimposed development and overbank. The sediment supply is the primary control factor of barrier and interlayer thickness, and the terrain slope change is the secondary factor. In conclusion, the development model of barriers and interlayers can be used to describe and predict the reservoir structure models under the same sedimentary background and provides a technical support for the exploration and development of deep-water oil and gas.

Abstract Aims Exosomes are known as nanovesicles that are naturally secreted, playing an essential role in stem-mediated cardioprotection. This study mainly focused on investigating if exosomes derived from miR-214 overexpressing mesenchymal stem cells (MSCs) show more valid cardioprotective ability in a rat model of acute myocardial infarction (AMI) and its potential mechanisms. Methods Exosomes were isolated from control MSCs (Ctrl-Exo) and miR-214 overexpressing MSCs (miR-214OE-Exo) and then they were delivered to cardiomyocytes and endothelial cells in vitro under hypoxia and serum deprivation (H/SD) condition or in vivo in an acutely infarcted Sprague-Dawley rat heart. Regulated genes and signal pathways by miR-214OE-Exo treatment were explored using western blot analysis and luciferase assay. Results in vitro , miR-214OE-Exo enhanced migration, tube-like formation in endothelial cells. In addition, miR-214OE-Exo ameliorated the survival of cardiomyocytes under H/SD. In the rat AMI model, compared to Ctrl-Exo, miR-214OE-Exo reduced myocardial apoptosis, and therefore reduced infarct size and improved cardiac function. Besides, miR-214OE-Exo accelerated angiogenesis in peri-infarct region. Mechanistically, we identified that exosomal miR-214-3p promoted cardiac repair via targeting PTEN and activating p-AKT signal pathway. Conclusion Exosomes derived from miR-214 overexpressing MSCs have greatly strengthened the therapeutic efficacy for treatment of AMI by promoting cardiomyocyte survival and endothelial cell function. Graphical abstract

Abstract Background Skeletal muscle is negatively impacted by conditions such as spaceflight or prolonged bed rest, resulting in a dramatic decline in muscle mass, maximum contractile force, and muscular endurance. Electrical stimulation (ES) is an essential tool in neurophysiotherapy and an effective means of preventing skeletal muscle atrophy and dysfunction. Historically, ES treatment protocols have used either low or high frequency electrical stimulation (LFES/HFES). However, our study tests the use of a combination of different frequencies in a single electrical stimulation intervention in order to determine a more effective protocol for improving both skeletal muscle strength and endurance. Methods An adult male SD rat model of muscle atrophy was established through 4 weeks of tail suspension (TS). To investigate the effects of different frequency combinations, the experimental animals were treated with low (20 Hz) or high (100 Hz) frequency before TS for 6 weeks, and during TS for 4weeks. The maximum contraction force and fatigue resistance of skeletal muscle were then assessed before the animals were sacrificed. The muscle mass, fiber cross-sectional area (CSA), fiber type and related protein expression were examined and analyzed to gain insights into the mechanisms by which the ES intervention protocol used in this study regulates muscle strength and endurance. Results After 4 weeks of unloading, the soleus muscle mass and fiber CSA decreased by 39% and 58% respectively, while the number of glycolytic muscle fibers increased by 21%. The gastrocnemius muscle fibers showed a 51% decrease in CSA, with a 44% decrease in single contractility and a 39% decrease in fatigue resistance. The number of glycolytic muscle fibers in the gastrocnemius also increased by 29%. However, the application of HFES either prior to or during unloading showed an improvement in muscle mass, fiber CSA, and oxidative muscle fibers. In the pre-unloading group, the soleus muscle mass increased by 62%, while the number of oxidative muscle fibers increased by 18%. In the during unloading group, the soleus muscle mass increased by 29% and the number of oxidative muscle fibers increased by 15%. In the gastrocnemius, the pre-unloading group showed a 38% increase in single contractile force and a 19% increase in fatigue resistance, while in the during unloading group, a 21% increase in single contractile force and a 29% increase in fatigue resistance was observed, along with a 37% and 26% increase in the number of oxidative muscle fibers, respectively. The combination of HFES before unloading and LFES during unloading resulted in a significant elevation of the soleus mass by 49% and CSA by 90%, with a 40% increase in the number of oxidative muscle fibers in the gastrocnemius. This combination also resulted in a 66% increase in single contractility and a 38% increase in fatigue resistance. Conclusion Our results indicated that using HFES before unloading can reduce the harmful effects of muscle unloading on the soleus and gastrocnemius muscles. Furthermore, we found that combining HFES before unloading with LFES during unloading was more effective in preventing muscle atrophy in the soleus and preserving the contractile function of the gastrocnemius muscle.

Aim: Diabetes osteoporosis (DOP) is a chronic bone metabolic disease induced by diabetes, whose morbidity continues to increase. Epimedium brevicornum Maxim (EB), a popular Chinese traditional medicine, has been used to treat bone diseases in China for thousands of years. But its material basis and specific mechanism of action are not clear. Methods: Epimedium brevicornum crude polysaccharide (EPE) is the main component, in this research the characterized the structure of EBPC1 purified from EPE was detected and its effects on cell proliferation, differentiation, and cytoskeletal in osteoblasts induced by high glucose. Results: The molecular weight of EBPC1 was 10.5 kDa. It was mainly comprised of glucose and galactose, and the backbone of EBPC1 was→4)-α-D-Galp-(1→4)-α-D-Galp-(1→6)-β-D-Galp-(1→6)-β-D-Galp-(1→4)-α-D-Glcp-(1→4)-α-D-Glcp-(1→. The results from in vitro experiments revealed that EBPC1 significantly increased alkaline phosphatase (ALP) activity and mineralized nodule formation in primary osteoblasts, also significantly up-regulated expression of Alp mRNA and Runx2 mRNA in the presence of EBPC1 pretreatment. Moreover, EBPC1 modulated apoptosis via the regulation of Bax/Bcl2. Conclusion: These results indicate that EBPC1 treatment can promote osteogenesis during DOP, which can ameliorate apoptosis by regulating Bax/Bcl2 and accelerating osteogenesis in osteoblasts.

In environments with a low signal-to-reverberation ratio (SRR) characterized by fluctuations in clutter number and distribution, particle filter-based tracking methods may experience significant fluctuations in the posterior probability of existence. This can lead to interruptions or even loss of the target trajectory. To address this issue, an adaptive PF-based tracking method (APF) with joint reverberation suppression is proposed. This method establishes the state space model under the Bayesian framework and implements it through particle filtering. To keep the weak target echoes, all the non-zero entries contained in the sparse matrix processed by the low-rank and sparsity decomposition (LRSD) are treated as the measurements. The prominent feature of this approach is introducing an adaptive measurement likelihood ratio (AMLR) into the posterior update step, which solves the problem of unstable tracking due to the strong fluctuation in the number of point measurements per frame. The proposed method is verified by four shallow water experimental datasets obtained by an active sonar with a uniform horizontal linear array. The results demonstrate that the tracking frame success ratio of the proposed method improved by over 14% compared with the conventional PF tracking method.

Summary: Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. It remains unclear how MIS-C phenotypes vary across SARS-CoV-2 variants. We aimed to investigate clinical characteristics and outcomes of MIS-C across SARS-CoV-2 eras. Methods: We performed a multicentre observational retrospective study including seven paediatric hospitals in four countries (France, Spain, U.K., and U.S.). All consecutive confirmed patients with MIS-C hospitalised between February 1st, 2020, and May 31st, 2022, were included. Electronic Health Records (EHR) data were used to calculate pooled risk differences (RD) and effect sizes (ES) at site level, using Alpha as reference. Meta-analysis was used to pool data across sites. Findings: Of 598 patients with MIS-C (61% male, 39% female; mean age 9.7 years [SD 4.5]), 383 (64%) were admitted in the Alpha era, 111 (19%) in the Delta era, and 104 (17%) in the Omicron era. Compared with patients admitted in the Alpha era, those admitted in the Delta era were younger (ES −1.18 years [95% CI −2.05, −0.32]), had fewer respiratory symptoms (RD −0.15 [95% CI −0.33, −0.04]), less frequent non-cardiogenic shock or systemic inflammatory response syndrome (SIRS) (RD −0.35 [95% CI −0.64, −0.07]), lower lymphocyte count (ES −0.16 × 109/uL [95% CI −0.30, −0.01]), lower C-reactive protein (ES −28.5 mg/L [95% CI −46.3, −10.7]), and lower troponin (ES −0.14 ng/mL [95% CI −0.26, −0.03]). Patients admitted in the Omicron versus Alpha eras were younger (ES −1.6 years [95% CI −2.5, −0.8]), had less frequent SIRS (RD −0.18 [95% CI −0.30, −0.05]), lower lymphocyte count (ES −0.39 × 109/uL [95% CI −0.52, −0.25]), lower troponin (ES −0.16 ng/mL [95% CI −0.30, −0.01]) and less frequently received anticoagulation therapy (RD −0.19 [95% CI −0.37, −0.04]). Length of hospitalization was shorter in the Delta versus Alpha eras (−1.3 days [95% CI −2.3, −0.4]). Interpretation: Our study suggested that MIS-C clinical phenotypes varied across SARS-CoV-2 eras, with patients in Delta and Omicron eras being younger and less sick. EHR data can be effectively leveraged to identify rare complications of pandemic diseases and their variation over time. Funding: None.

Summary: Background: Characterizing Post-Acute Sequelae of COVID (SARS-CoV-2 Infection), or PASC has been challenging due to the multitude of sub-phenotypes, temporal attributes, and definitions. Scalable characterization of PASC sub-phenotypes can enhance screening capacities, disease management, and treatment planning. Methods: We conducted a retrospective multi-centre observational cohort study, leveraging longitudinal electronic health record (EHR) data of 30,422 patients from three healthcare systems in the Consortium for the Clinical Characterization of COVID-19 by EHR (4CE). From the total cohort, we applied a deductive approach on 12,424 individuals with follow-up data and developed a distributed representation learning process for providing augmented definitions for PASC sub-phenotypes. Findings: Our framework characterized seven PASC sub-phenotypes. We estimated that on average 15.7% of the hospitalized COVID-19 patients were likely to suffer from at least one PASC symptom and almost 5.98%, on average, had multiple symptoms. Joint pain and dyspnea had the highest prevalence, with an average prevalence of 5.45% and 4.53%, respectively. Interpretation: We provided a scalable framework to every participating healthcare system for estimating PASC sub-phenotypes prevalence and temporal attributes, thus developing a unified model that characterizes augmented sub-phenotypes across the different systems. Funding: Authors are supported by National Institute of Allergy and Infectious Diseases, National Institute on Aging, National Center for Advancing Translational Sciences, National Medical Research Council, National Institute of Neurological Disorders and Stroke, European Union, National Institutes of Health, National Center for Advancing Translational Sciences.

Stocking of filter-feeding fish (mainly Hypophthalmichthys molitrix and Aristichthys nobilis) is a common method used in lakes and reservoirs in (sub)tropical China to control phytoplankton, but the results are ambiguous and lack long-term data to support. We analysed a decade (2010-2020) of monitoring data from a subtropical plateau reservoir, southwest China, to which filter-feeding fish were stocked annually. We found that the total phytoplankton biomass, cyanobacteria biomass and average individual mass of phytoplankton decreased significantly during the study period despite absence of nutrient concentration reduction. However, the grazing pressure of zooplankton on phytoplankton also decreased markedly as judged from changes in the ratio of zooplankton biomass to phytoplankton biomass and Daphnia proportion of total zooplankton biomass. This is likely a response to increasing predation on zooplankton by the stocked fish. Our results also indicated that water temperature, total phosphorus and water level promoted phytoplankton growth. Our results revealed that filter-feeding fish contributed to the decline in the biomass of phytoplankton but that it also had a strong negative effect on the grazing pressure of zooplankton on phytoplankton, even in this deep reservoir where zooplankton may have a better chance of survival through vertical migration. The particular strong effect on zooplankton is most likely due to imbalance of stocking and harvesting of fish. In the management of eutrophic reservoirs, the reduction of external nutrient loading should have highest priority. In highland (low temperature) deep-water eutrophic reservoirs, stocking of filter-feeding fish may help to control filamentous phytoplankton provided that the fish stocking is properly managed. The optimal stocking intensity of filter-feeding fish that can help control phytoplankton in such reservoirs without excessive impact on large-bodied zooplankton is a topic for further elucidation, however.

Abstract Cerium manganese bimetallic catalysts have become the focus of current research because of their excellent catalytic performance for soot combustion. Two series of cerium manganese catalysts (Na-free catalysts and Na-containing catalysts) were prepared by coprecipitation method and characterized using XRD, N2 adsorption–desorption, SEM, Raman, XPS, H2-TPR, O2-TPD, Soot-TPR-MS and in situ IR. The effects of abundant oxygen vacancies and surface highly dispersed MnO x on soot catalytic combustion of cerium manganese catalysts prepared by different precipitants were analyzed. The activity test results show that the active oxygen species released by a large number of oxygen vacancies in the cerium manganese catalyst are more favorable to the soot catalytic combustion than MnO x which is highly dispersed on the surface of the catalyst and has good redox performance at low temperature. Because the catalytic effect of MnO x on the surface of Na-free catalysts is more dependent on the contact condition between the catalyst and the soot, this phenomenon can be observed more easily under the loose contact condition than under the tight contact condition. The activity cycle test results show that these two series of catalysts show good stability and repeated use will hardly cause any deactivation of the catalysts.

Triggering receptor expressed on myeloid cells-like 2 (TREML2) is a newly identified susceptibility gene for Alzheimer’s disease (AD). It encodes a microglial inflammation-associated receptor. To date, the potential role of microglial TREML2 in neuroinflammation in the context of AD remains unclear. In this study, APP/PS1 mice were used to investigate the dynamic changes of TREML2 levels in brain during AD progression. In addition, lipopolysaccharide (LPS) stimulation of primary microglia as well as a lentivirus-mediated TREML2 overexpression and knockdown were employed to explore the role of TREML2 in neuroinflammation in the context of AD. Our results show that TREML2 levels gradually increased in the brains of APP/PS1 mice during disease progression. LPS stimulation of primary microglia led to the release of inflammatory cytokines including interleukin-1β, interleukin-6, and tumor necrosis factor-α in the culture medium. The LPS-induced microglial release of inflammatory cytokines was enhanced by TREML2 overexpression and was attenuated by TREML2 knockdown. LPS increased the levels of microglial M1-type polarization marker inducible nitric oxide synthase. This effect was enhanced by TREML2 overexpression and ameliorated by TREML2 knockdown. Furthermore, the levels of microglial M2-type polarization markers CD206 and ARG1 in the primary microglia were reduced by TREML2 overexpression and elevated by TREML2 knockdown. LPS stimulation increased the levels of NLRP3 in primary microglia. The LPS-induced increase in NLRP3 was further elevated by TREML2 overexpression and alleviated by TREML2 knockdown. In summary, this study provides the first evidence that TREML2 modulates inflammation by regulating microglial polarization and NLRP3 inflammasome activation. These findings reveal the mechanisms by which TREML2 regulates microglial inflammation and suggest that TREML2 inhibition may represent a novel therapeutic strategy for AD.

Abstract Acute ischemic stroke (AIS) is a global cerebrovascular disease with high disability and mortality, which has no effective therapy. Studies have demonstrated that astrocyte-derived exosomes (ADEXs) provided neuroprotection in experimental stroke models. Nevertheless, the role of exosomes derived from oxygen-glucose-deprivation/reoxygenation-stimulated astrocytes (OGD/R-stimulated astrocytes; OGD/R-ADEXs) in AIS remains largely unknown. Here, we found that OGD/R-ADEXs significantly reduced OGD/R-induced neuronal death and promoted neuronal autophagy. These effects were reversed when astrocytes were pretreated with GW4869, an exosome secretion inhibitor, or when hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) was knocked down. Neuroprotection was also observed during treatment with OGD/R-ADEXs in vivo. Further studies showed that Nampt, played a vital effect in the regulation of autophagy, was significantly increased in OGD/R-ADEXs. Knockdown of Nampt in astrocytes abolished the above-mentioned effects of OGD/R-ADEXs. Mechanistically, Nampt increased autophagy and decreased cell death by modulating AMPK/mTOR signaling, which recognized as a key signaling pathway of autophagy after AIS. Collectively, these results showed that Nampt released by OGD/R-ADEXs ameliorated acute ischemic stroke during neuronal injury by targeting AMPK/mTOR signaling to induce autophagy. Our study revealed a new key factor in the secretion of exosomes by OGD/R astrocytes, which regulated autophagy and induced neuroprotection in a mouse stroke model.

Abstract Alzheimer’s disease (AD) is one of the major neurodegenerative diseases and the most common form of dementia. Characterized by the loss of learning, memory, problem-solving, language, and other thinking abilities, AD exerts a detrimental effect on both patients’ and families’ quality of life. Although there have been significant advances in understanding the mechanism underlying the pathogenesis and progression of AD, there is no cure for AD. The failure of numerous molecular targeted pharmacologic clinical trials leads to an emerging research shift toward non-invasive therapies, especially multiple targeted non-invasive treatments. In this paper, we reviewed the advances of the most widely studied non-invasive therapies, including photobiomodulation (PBM), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and exercise therapy. Firstly, we reviewed the pathological changes of AD and the challenges for AD studies. We then introduced these non-invasive therapies and discussed the factors that may affect the effects of these therapies. Additionally, we review the effects of these therapies and the possible mechanisms underlying these effects. Finally, we summarized the challenges of the non-invasive treatments in future AD studies and clinical applications. We concluded that it would be critical to understand the exact underlying mechanisms and find the optimal treatment parameters to improve the translational value of these non-invasive therapies. Moreover, the combined use of non-invasive treatments is also a promising research direction for future studies and sheds light on the future treatment or prevention of AD.

Torsemide is commonly used to relieve edema during the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (ATO). We explored the effect of torsemide on the plasma concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMAV) and dimethyarsinic acid (DMAV) in APL patients treated with ATO and clarified its molecular mechanism in rats and cells. The study included 146 APL patients treated with ATO. 60（41.1 %) of these 146 patients were co-administered with torsemide. The treatment of torsemide increased plasma concentrations of iAs (P

Bi-activated photonic materials are promising for various applications in high-capacity telecommunication, tunable laser, and advanced bioimaging and sensing. Although various Bi-doped material candidates have been explored, manufacturing of Bi heavily doped fiber with excellent optical activity remains a long-standing challenge. Herein, a novel viscosity evolutional behavior mediated strategy for manufacturing of Bi-doped active fiber with high dopant solubility is proposed. The intrinsic relation among the evolution of Bi, reaction temperature and viscosity of the glass system is established. Importantly, the effective avenue to prevent the undesired deactivation of Bi during fiber drawing by tuning the temperature dependent viscosity evolution is built. By applying the strategy, for the first time we demonstrate the success in fabrication of heavily doped Bi active fiber. Furthermore, the principal fiber amplifier device is constructed and broadband optical signal amplification is realized. Our findings indicate the effectiveness of the proposed temperature dependent viscosity mediated strategy for developing novel photonic active fiber, and they also demonstrate the great potential for application in the next-generation high-capacity telecommunication system.

Low-dose aspirin (LDA) is efficacious in preventing preeclampsia, but its mechanism of action is unclear. Conflicting evidence suggests that it may inhibit placental trophoblast release of soluble fms-like tyrosine kinase-1 (sFlt1), a key mediator of preeclampsia. We examined whether, and at what concentrations, aspirin and its principal metabolite, salicylic acid, modulate sFlt1 release and/or expression in trophoblasts. Human trophoblast lines BeWo and HTR-8/SVneo were cultured; BeWo cells were also treated with 1% oxygen vs. normoxia to mimic hypoxia in preeclamptic placentas. Cells were treated with aspirin or salicylic acid vs. vehicle for 24 h at concentrations relevant to LDA and at higher concentrations. Protein concentrations (ELISA) and mRNA expression (RT-PCR) of sFlt1 were determined. Under normoxia, LDA-relevant concentrations of aspirin (10–50 µmol/L) or salicylic acid (20–100 µmol/L) had no significant effect on sFlt1 protein release or mRNA expression in BeWo cells. However, inhibition was observed at higher concentrations (1 mmol/L for aspirin and ≥200 μmol/L for salicylic acid). Hypoxia enhanced sFlt1 protein release and mRNA expression in BeWo cells, but these responses were not significantly affected by either aspirin or salicylic acid at LDA concentrations. Similarly, neither drug altered sFlt1 protein secretion or mRNA expression in normoxic HTR-8/SVneo cells at LDA concentrations. We suggest that direct modulation of trophoblast release or expression of sFlt1 is unlikely to be a mechanism underlying the clinical efficacy of LDA in preeclampsia.

Abstract Automatic and robust target depth estimation is an important issue of an active detection system working in the reliable acoustic path (RAP) environment. In this paper, the target depth‐sensitive acoustic interference structure is used as input, and a deep neural network (DNN) method is proposed to realize automatic depth estimation. Furthermore, to improve the robustness of the network, both the sound speed profile (SSP) uncertainty and the target trajectory uncertainty are considered in the training dataset. The former is modelled as a random weighted sum of the empirical orthogonal function (EOF), and the latter is modelled by the partial‐data‐lacking of the network input. The method was evaluated through simulated data and compared with the conventional method of matching the measured interference structure with the replicas. The presented method exhibits a higher accuracy of depth estimate in uncertain environments when the signal‐to‐noise ratio (SNR) is higher than −6 dB, but its performance deteriorates rapidly as the SNR decreases further. The method is also verified by semi‐simulation with experimental data in deep water.

Abstract Integrating data across institutions can improve learning efficiency. To integrate data efficiently while protecting privacy, we propose A one-shot, summary-statistics-based, Distributed Algorithm for fitting Penalized (ADAP) regression models across multiple datasets. ADAP utilizes patient-level data from a lead site and incorporates the first-order (ADAP1) and second-order gradients (ADAP2) of the objective function from collaborating sites to construct a surrogate objective function at the lead site, where model fitting is then completed with proper regularizations applied. We evaluate the performance of the proposed method using both simulation and a real-world application to study risk factors for opioid use disorder (OUD) using 15,000 patient data from the OneFlorida Clinical Research Consortium. Our results show that ADAP performs nearly the same as the pooled estimator but achieves higher estimation accuracy and better variable selection than the local and average estimators. Moreover, ADAP2 successfully handles heterogeneity in covariate distributions.

Abstract Integrating real-world data (RWD) from several clinical sites offers great opportunities to improve estimation with a more general population compared to analyses based on a single clinical site. However, sharing patient-level data across sites is practically challenging due to concerns about maintaining patient privacy. We develop a distributed algorithm to integrate heterogeneous RWD from multiple clinical sites without sharing patient-level data. The proposed distributed conditional logistic regression (dCLR) algorithm can effectively account for between-site heterogeneity and requires only one round of communication. Our simulation study and data application with the data of 14,215 COVID-19 patients from 230 clinical sites in the UnitedHealth Group Clinical Research Database demonstrate that the proposed distributed algorithm provides an estimator that is robust to heterogeneity in event rates when efficiently integrating data from multiple clinical sites. Our algorithm is therefore a practical alternative to both meta-analysis and existing distributed algorithms for modeling heterogeneous multi-site binary outcomes.

IntroductionSuicide is the tenth leading cause of death in the United States and continues to be a major public health concern. Suicide risk is highly prevalent among individuals with co-occurring substance use disorders (SUD) and mental health disorders, making them more prone to adverse substance use related outcomes including overdose. Identifying individuals with SUD who are suicidal, and therefore potentially most at risk of overdose, is an important step to address the synergistic epidemics of suicides and overdose fatalities in the United States. The current study assesses whether patterns of suicidality endorsement can indicate risk for substance use and overdose.MethodsLatent class analysis (LCA) was used to assess patterns of item level responses to the Concise Health Risk Tracking Self-Report (CHRT-SR), which measures thoughts and feelings associated with suicidal propensity. We used data from 2,541 participants with SUD who were enrolled across 8 randomized clinical trials in the National Drug Abuse Treatment Clinical Trials Network from 2012 to 2021. Characteristics of individuals in each class were assessed, and multivariable logistic regression was performed to examine class membership as a predictor of overdose. LCA was also used to analyze predictors of substance use days.ResultsThree classes were identified and discussed: Class (1) Minimal Suicidality, with low probabilities of endorsing each CHRT-SR construct; Class (2) Moderate Suicidality, with high probabilities of endorsing pessimism, helplessness, and lack of social support, but minimal endorsement of despair or suicidal thoughts; and Class (3) High Suicidality with high probabilities of endorsing all constructs. Individuals in the High Suicidality class comprise the highest proportions of males, Black/African American individuals, and those with a psychiatric history and baseline depression, as compared with the other two classes. Regression analysis revealed that those in the High Suicidality class are more likely to overdose as compared to those in the Minimal Suicidality class (p = 0.04).ConclusionSuicidality is an essential factor to consider when building strategies to screen, identify, and address individuals at risk for overdose. The integration of detailed suicide assessment and suicide risk reduction is a potential solution to help prevent suicide and overdose among people with SUD.

IntroductionPatients with diabetes and comorbid substance use disorders (SUD) experience poor diabetes management, increased medical complications and mortality. However, research has documented that patients engaged in substance abuse treatment have better management of their comorbid conditions. The current study examines diabetes management among patients with type 2 diabetes, with and without comorbid SUD, receiving care at Florida-based Federally Qualified Health Centers (FQHC) of Health Choice Network (HCN).MethodsA retrospective analysis was conducted using deidentified electronic health records of 37,452 patients with type 2 diabetes who received care at a HCN site in Florida between 2016 and 2019. A longitudinal logistic regression analysis examined the impact of SUD diagnosis on achievement of diabetes management [HbA1c < 7.0% (53 mmol/mol)] over time. A secondary analysis evaluated, within those with an SUD diagnosis, the likelihood of HbA1c control between those with and without SUD treatment.ResultsThe longitudinal assessment of the relationship between SUD status and HbA1c control revealed that those with SUD (N = 6,878, 18.4%) were less likely to control HbA1c over time (OR = 0.56; 95% CI = 0.49–0.63). Among those with SUD, patients engaged in SUD treatment were more likely to control HbA1c (OR = 5.91; 95% CI = 5.05–6.91).DiscussionFindings highlight that untreated SUD could adversely affect diabetes control and sheds light on the opportunity to enhance care delivery for patients with diabetes and co-occurring SUD.

The method of extracting protein from corn steep liquor by isoelectric point method was studied. The supernatant after extracting crude protein was used to produce single cell protein. Single factor experiment was used to analyze the influence of pH, temperature and time on protein extraction. Response surface methodology was used to determine the optimal process of isoelectric point extraction of protein. The conditions for the production of single cell protein from the supernatant of Saccharomyces cerevisiae and Candida utilis were studied. The results showed that the optimum conditions for crude protein extraction by isoelectric point method were as follows: pH 7.6, extraction temperature 26.4 ℃ and extraction time 20 min. The extraction rate was 77.5%. The conditions for producing single cell protein from the supernatant after extracting crude protein were as follows: Candida utilis was better than Saccharomyces cerevisiae. When the dry matter concentration in the supernatant was 8% and pH was 5.5, the colony number obtained by Candida utilis fermentation reached 1.6×109 CFU/mL.

Abstract We developed a One-shot Distributed Algorithm for Cox proportional-hazards model to analyze Heterogeneous multi-center time-to-event data (ODACH) circumventing the need for sharing patient-level information across sites. This algorithm implements a surrogate likelihood function to approximate the Cox log-partial likelihood function that is stratified by site using patient-level data from a lead site and aggregated information from other sites, allowing the baseline hazard functions and the distribution of covariates to vary across sites. Simulation studies and application to a real-world opioid use disorder study showed that ODACH provides estimates close to the pooled estimator, which analyzes patient-level data directly from all sites via a stratified Cox model. Compared to the estimator from meta-analysis, the inverse variance-weighted average of the site-specific estimates, ODACH estimator demonstrates less susceptibility to bias, especially when the event is rare. ODACH is thus a valuable privacy-preserving and communication-efficient method for analyzing multi-center time-to-event data.

Sn-doped graphene nanoplatelets (GnPSn) was successfully synthesized by wet ball milling method from expandable graphite and Sn powder. The surface morphology, thickness, crystal structure and chemical structure were comprehensive characterized. Epoxy resin (EP) composites (EP/GnPSn or EP/HPCTP/GnPSn) were prepared by adding GnPSn alone or GnPSn and hexaphenoxy cyclotriphosphazene (HPCTP) together to EP to improve the fire resistance and smoke suppression. EP/6.3wt%HPCTP/2.7wt%GnPSn composite had the best flame retardancy with LOI value of 33.6%, UL-94 of V 0 grade, peak heat release rate and total heat release reduced by 44.80% and 23.93%, respectively. The results of thermogravimetry analysis, Raman spectroscopy and Fourier transform infrared spectroscopy showed that HPCTP and GnPSn can react to form Sn–O–P bonds to promote the compactness of the residual char in condensed phase, thereby preventing the combustion of EP matrix.

A lossless, one-shot and privacy-preserving distributed algorithm was revealed for fitting linear mixed models on multi-site data. The algorithm was applied to a study of 120,609 COVID-19 patients using only minimal aggregated data from each of 14 sites.

Large collaborative research networks provide opportunities to jointly analyze multicenter electronic health record (EHR) data, which can improve the sample size, diversity of the study population, and generalizability of the results. However, there are challenges to analyzing multicenter EHR data including privacy protection, large-scale computation resource requirements, heterogeneity across sites, and correlated observations. In this paper, we propose a federated algorithm for generalized linear mixed models (Fed-GLMM), which can flexibly model multicenter longitudinal or correlated data while accounting for site-level heterogeneity. Fed-GLMM can be applied to both federated and centralized research networks to enable privacy-preserving data integration and improve computational efficiency. By communicating a limited amount of summary statistics, Fed-GLMM can achieve nearly identical results as the gold-standard method where the GLMM is directly fitted to the pooled dataset. We demonstrate the performance of Fed-GLMM in numerical experiments and an application to longitudinal EHR data from multiple healthcare facilities.

Summary: Background: While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking. Methods: A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1–365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021. Findings: Advanced age (HR 2.77, 95%CI 2.53–3.04, p

Abstract Background Network meta-analysis (NMA) is a widely used tool to compare multiple treatments by synthesizing different sources of evidence. Measures such as the surface under the cumulative ranking curve (SUCRA) and the P-score are increasingly used to quantify treatment ranking. They provide summary scores of treatments among the existing studies in an NMA. Clinicians are frequently interested in applying such evidence from the NMA to decision-making in the future. This prediction process needs to account for the heterogeneity between the existing studies in the NMA and a future study. Methods This article introduces the predictive P-score for informing treatment ranking in a future study via Bayesian models. Two NMAs were used to illustrate the proposed measure; the first assessed 4 treatment strategies for smoking cessation, and the second assessed treatments for all-grade treatment-related adverse events. For all treatments in both NMAs, we obtained their conventional frequentist P-scores, Bayesian P-scores, and predictive P-scores. Results In the two examples, the Bayesian P-scores were nearly identical to the corresponding frequentist P-scores for most treatments, while noticeable differences existed for some treatments, likely owing to the different assumptions made by the frequentist and Bayesian NMA models. Compared with the P-scores, the predictive P-scores generally had a trend to converge toward a common value of 0.5 due to the heterogeneity. The predictive P-scores’ numerical estimates and the associated plots of posterior distributions provided an intuitive way for clinicians to appraise treatments for new patients in a future study. Conclusions The proposed approach adapts the existing frequentist P-score to the Bayesian framework. The predictive P-score can help inform medical decision-making in future studies.

Abstract Clinical research networks (CRNs), made up of multiple healthcare systems each with patient data from several care sites, are beneficial for studying rare outcomes and increasing generalizability of results. While CRNs encourage sharing aggregate data across healthcare systems, individual systems within CRNs often cannot share patient-level data due to privacy regulations, prohibiting multi-site regression which requires an analyst to access all individual patient data pooled together. Meta-analysis is commonly used to model data stored at multiple institutions within a CRN but can result in biased estimation, most notably in rare-event contexts. We present a communication-efficient, privacy-preserving algorithm for modeling multi-site zero-inflated count outcomes within a CRN. Our method, a one-shot distributed algorithm for performing hurdle regression (ODAH), models zero-inflated count data stored in multiple sites without sharing patient-level data across sites, resulting in estimates closely approximating those that would be obtained in a pooled patient-level data analysis. We evaluate our method through extensive simulations and two real-world data applications using electronic health records: examining risk factors associated with pediatric avoidable hospitalization and modeling serious adverse event frequency associated with a colorectal cancer therapy. In simulations, ODAH produced bias less than 0.1% across all settings explored while meta-analysis estimates exhibited bias up to 12.7%, with meta-analysis performing worst in settings with high zero-inflation or low event rates. Across both applied analyses, ODAH estimates had less than 10% bias for 18 of 20 coefficients estimated, while meta-analysis estimates exhibited substantially higher bias. Relative to existing methods for distributed data analysis, ODAH offers a highly accurate, computationally efficient method for modeling multi-site zero-inflated count data.

Developing novel scintillating glass with high density and intense radioluminescence is of critical importance for various radiation-related technologies. In this paper, Tb-doped Gd2O3-WO3-SiO2 (GWS) scintillating glass was prepared and investigated. The optical and scintillation properties are explored. And the optimal concentration of Tb activators in glass excited by UV-light and X-ray is determined. Moreover, annealing glass enables a unique glass bleaching phenomenon. Benefitting from the increasement in transparency, a notable improvement in photoluminescence (~195% enhancement in intensity) and radioluminescence (~146% enhancement in intensity) could be realized. The optical and structural characterizations reveal a dramatic change of W chemical valance state from W5+ to W6+, which is supposed to govern the decoloring process. Our research indicates that Tb-doped GWS scintillating glass can be a potential candidate for X-ray monitoring.

The Lintong–Chang’an Fault Zone (LCFZ) is an important active structure in the Weihe Graben (central China). The study on the activity of the LCFZ is not only of great significance to explore the regional tectonic mechanism, but also has practical value in urban seismic mitigation and disaster relief. In this study, based on high-resolution remotely sensed imagery, shallow seismic reflection survey, borehole data and excavation of a foundation pit, we determined the distribution and activity of the Wangjiabian–Houjiawan fault (a branch fault of the LCFZ) in the Shaoling Loess Tableland. Combined with previous studies, we further inferred that the vertical displacements were 0–6 m along the LCFZ, but most displacements were around 1 m. Furthermore, there are eight locations where no displacements have been found in the Late Pleistocene strata. The offsets on the fault zone since the Late Pleistocene display a wave-like pattern, which is unrelated to the regional topographic expression. Compared to other faults in the Weihe Graben, the activity of the LCFZ in vertical component is relatively weak, implying a possible strike–slip motion. In addition, a major active fault may exist on the northwest side of this fault zone, bearing part of the fault motion in this region.

Vascular dementia is a type of dementia from brain damage caused by cerebrovascular lesions and vascular risk factors. Prevotella histicola is a species of Prevotella, belonging to the category of obligate anaerobe. The purpose of our work was to study the protection of Prevotella histicola on cognitive function in rats subjected to vascular dementia (VaD) and investigate underlying molecular mechanisms. The rats were randomly divided into three groups: control group, 2VO group and 2VO + Prevotella histicola group. The VaD rats (the 2VO group and 2VO + Prevotella histicola group) were generated by bilateral common carotid artery occlusion (2VO). Rats in the 2VO+ Prevotella histicola group were administered with Prevotella histicola twice daily. In comparison with the rats in the 2VO group, rats in the 2VO + Prevotella histicola group presented an enhanced cognitive ability, increased synapse-associated protein expression, a downregulation of proinflammatory factors and an upregulation of neurotrophic factors. The relevant mechanism of the protective effect of Prevotella histicola may be associated with the inhibition of glial cell-associated inflammation by regulating phosphorylation of CaMKII. In conclusion, Prevotella histicola attenuates neurological impairments via regulating synapse-associated protein expression and the liberation of inflammatory elements in vascular dementia rats. The findings above might benefit the development of Prevotella histicola transplantation as a promising treatment of VaD.

Despite significant advances of the bovine epigenome investigation, new evidence for the epigenetic basis of fetal cartilage development remains lacking. In this study, the chondrocytes were isolated from long bone tissues of bovine fetuses at 90 days. The Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) and transcriptome sequencing (RNA-seq) were used to characterize gene expression and chromatin accessibility profile in bovine chondrocytes. A total of 9686 open chromatin regions in bovine fetal chondrocytes were identified and 45% of the peaks were enriched in the promoter regions. Then, all peaks were annotated to the nearest gene for Gene Ontology (GO) and Kyoto Encylopaedia of Genes and Genomes (KEGG) analysis. Growth and development-related processes such as amide biosynthesis process (GO: 0043604) and translation regulation (GO: 006417) were enriched in the GO analysis. The KEGG analysis enriched endoplasmic reticulum protein processing signal pathway, TGF-β signaling pathway and cell cycle pathway, which are closely related to protein synthesis and processing during cell proliferation. Active transcription factors (TFs) were enriched by ATAC-seq, and were fully verified with gene expression levels obtained by RNA-seq. Among the top50 TFs from footprint analysis, known or potential cartilage development-related transcription factors FOS, FOSL2 and NFY were found. Overall, our data provide a theoretical basis for further determining the regulatory mechanism of cartilage development in bovine.

Abstract Background Asymptomatic infections may play an important role in severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) Delta variant transmissions. However, the immunologic features of asymptomatic postvaccination infections with the Delta variant of SARS‐CoV‐2 in adults remain to be defined. Methods A retrospective study involving 36 vaccinated adults infected with the SARS‐CoV‐2 Delta variant was performed. Their demographic and laboratory data were collected and analyzed in The First People's Hospital of Jingmen from August 4 to 20, 2021. Results Of the 36 adults, 6 persons had an asymptomatic infection. The severity of the SARS‐CoV‐2 infections was highly correlated with the doses of vaccinations (p = 0.019). The symptomatic and asymptomatic infected SARS‐CoV‐2 adults showed normal levels of leukocytes and lymphocytes. The C‐reactive protein (CRP) and interleukin‐6 (IL‐6) levels were elevated in the symptomatic groups. The period between the last vaccination to the time of infection in the asymptomatic group was longer than that in the mild and moderate groups (73 vs. 61 vs. 50 days; p = 0.047). The percentage of suppressor T‐cells in the asymptomatic group was the highest (32.2 ± 4.0% vs. 22.0 ± 7.2% vs. 29.3 ± 8.0%; p = 0.004). The signal‐to‐cutoff ratio value of total antibody against SARS‐CoV‐2 in the asymptomatic group was lower than that in the other two groups (383 vs. 703 vs. 1792; p

The identification of forest pests is of great significance to the prevention and control of the forest pests' scale. However, existing datasets mainly focus on common objects, which limits the application of deep learning techniques in specific fields (such as agriculture). In this paper, we collected images of forestry pests and constructed a dataset for forestry pest identification, called Forestry Pest Dataset. The Forestry Pest Dataset contains 31 categories of pests and their different forms. We conduct several mainstream object detection experiments on this dataset. The experimental results show that the dataset achieves good performance on various models. We hope that our Forestry Pest Dataset will help researchers in the field of pest control and pest detection in the future.

PurposeHost immunity influences the impact of cancer therapy but the effect of immune status in radioiodine (RAI)-treated differentiated thyroid cancer (DTC) remains obscure. Here we investigated indoleamine 2,3-dioxygenase (IDO) activity as a biomarker of response to RAI in patients with distant metastatic DTC (dmDTC).MethodsPatients with dmDTC receiving RAI were evaluated for serum IDO activity (kynurenine and kynurenine:tryptophan ratio) at baseline and 3 months after RAI. The optimal cut-off value for these biomarkers to predict response was established by receiver operating characteristic analysis. The relationship between disease outcomes, overall survival (OS) and progression-free survival (PFS), and IDO activity levels was studied.ResultsHigher baseline kynurenine:tryptophan ratio (>2.46) was correlated with poorer RAI response as well as shorter median PFS (45 mo versus not reached, p=0.002) and OS (78 mo versus not reached, p=0.035). High baseline kynurenine:tryptophan ratio was also correlated with a reduced number of tumor-infiltrating lymphocytes. Higher post/pre-kynurenine ratio (>1.69) was associated with survival endpoints: shorter median PFS (48 mo versus not reached, p=0.002) and OS (68 mo versus not reached, p=0.010). Favorable baseline and favorable change corresponded with better PFS and OS.ConclusionsOur results suggest that RAI also alters IDO activity in dmDTC patients. IDO activity could predict progression and survival outcomes for advanced dmDTC patients. Serum IDO biomarker levels could be used to select dmDTC likely to benefit from RAI therapy, although further studies are necessary.