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Abstract Background The current review aims to explore the evidence regarding the effectiveness of mandibular advancement orthodontic appliances with maxillary expansion device in treating pediatric Obstructive Sleep Apnea (OSA). Materials and methods A systematic literature search was conducted across PubMed, Cochrane Central, Web of Science, Embase, Scopus databases, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, and Wanfang. The research involved children and adolescents (under 16 years old) who received mandibular advancement and maxillary expansion functional orthopedic appliances for OSA treatment. We performed narrative reviews and subsequently amalgamated the findings from the studies. Results Six articles were included for review. Although a small number of studies were included, the research suggested the potential advantages of mandibular advancement for children with OSA. Following treatment, there was a decrease in AHI/RDI, an improvement in sleep quality, and the increase in oxygen saturation. Conclusions The limited quantity and quality of existing studies necessitate caution when drawing conclusions about the effectiveness of mandibular advancement and maxillary expansion for OSA. In the future, larger and well-designed randomized controlled trials (RCTs) are needed to provide more robust evidence. Patients should be carefully selected, and their orthodontic indications should be thoroughly evaluated before inclusion in such trials.We encourage researchers to design studies that monitor patients over several years to provide a comprehensive understanding of the long-term effectiveness. Trial registration This study was registered in PROSPERO(CRD42023480407) on November 20, 2023.

Abstract Background Postoperative time to extubation plays a role in prognosis after heart valve surgery; however, its exact impact has not been clarified. This study compared the postoperative outcomes of minimally invasive surgery and conventional sternotomy, focusing on early extubation and factors influencing prolonged mechanical ventilation. Methods Data from 744 patients who underwent heart valve surgery at the Zhejiang Provincial People’s Hospital between August 2019 and June 2022 were retrospectively analyzed. The outcomes in patients who underwent conventional median sternotomy (MS) and minimally invasive (MI) video-assisted thoracoscopic surgery were compared using inverse probability of treatment weighting (IPTW) and Kaplan–Meier curves. Clinical data, including surgical data, postoperative cardiac function, postoperative complications, and intensive care monitoring data, were analyzed. Results After propensity score matching and IPTW, 196 cases of conventional MS were compared with 196 cases of MI video-assisted thoracoscopic surgery. Compared to patients in the conventional MS group, those in the MI video-assisted thoracoscopic surgery group in the matched cohort had a higher early postoperative extubation rate (P

Abstract Objective To evaluate the trend of alcohol use disorder (AUD) mortality as a percentage of all-cause mortality in Canada and the United States (US) between 2000 and 2019, by age group. Results Joinpoint regression showed that AUD mortality as a percentage of all-cause mortality significantly increased between 2000 and 2019 in both countries, and across all age groups (i.e., young adults (20–34 years), middle-aged adults (35–49 years), and older adults (50 + years)). The trend has been levelling off, and even reversing in some cases, in recent years. The average annual percentage change differed across countries and between age groups, with a greater increase among Canadian adults aged 35–49 years and among adults aged 50 + years in the US. Over the past two decades, AUD mortality as a percentage of all-cause mortality has been increasing among all adults in both Canada and the US.

Abstract Introduction This study examines the association between healthcare indicators and hospitalization rates in three high-income European countries, namely Estonia, Latvia, and Lithuania, from 2015 to 2020. Method We used a sex-stratified generalized additive model (GAM) to investigate the impact of select healthcare indicators on hospitalization rates, adjusted by general economic status—i.e., gross domestic product (GDP) per capita. Results Our findings indicate a consistent decline in hospitalization rates over time for all three countries. The proportion of health expenditure spent on hospitals, the number of physicians and nurses, and hospital beds were not statistically significantly associated with hospitalization rates. However, changes in the number of employed medical doctors per 10,000 population were statistically significantly associated with changes of hospitalization rates in the same direction, with the effect being stronger for males. Additionally, higher GDP per capita was associated with increased hospitalization rates for both males and females in all three countries and in all models. Conclusions The relationship between healthcare spending and declining hospitalization rates was not statistically significant, suggesting that the healthcare systems may be shifting towards primary care, outpatient care, and on prevention efforts.

Abstract Background Neutrophils are granulocytes with essential antimicrobial effector functions and short lifespans. During infection or sterile inflammation, emergency granulopoiesis leads to release of immature neutrophils from the bone marrow, serving to boost circulating neutrophil counts. Steady state and emergency granulopoiesis are incompletely understood, partly due to a lack of genetically amenable models of neutrophil development. Methods We optimised a method for ex vivo production of human neutrophils from CD34+ haematopoietic progenitors. Using flow cytometry, we phenotypically compared cultured neutrophils with native neutrophils from donors experiencing emergency granulopoiesis, and steady state neutrophils from non-challenged donors. We carry out functional and proteomic characterisation of cultured neutrophils and establish genome editing of progenitors. Results We obtain high yields of ex vivo cultured neutrophils, which phenotypically resemble immature neutrophils released into the circulation during emergency granulopoiesis. Cultured neutrophils have similar rates of ROS production and bacterial killing but altered degranulation, cytokine release and antifungal activity compared to mature neutrophils isolated from peripheral blood. These differences are likely due to incomplete synthesis of granule proteins, as demonstrated by proteomic analysis. Conclusion Ex vivo cultured neutrophils are genetically tractable via genome editing of precursors and provide a powerful model system for investigating the properties and behaviour of immature neutrophils.

Abstract C57BL/6 mice are frequently utilized as murine models with the desired genetic background for altertion in multiple research contexts. So far, there is still a lack of comprehensive kidney morphology and single-cell transcriptome atlas at all stages of growth of C57BL/6 mice. To provide an interactive set of reference standards for the scientific community, we performed the current study to investigate the kidney’s development throughout the capillary-loop stage until senescence. Eight groups, with five to six mice each, represented embryonic stage (embryos 18.5 days), suckling period (1 day after birth), juvenile stage (1 month old), adulthood (containing 3 months old, 6 months old and 10 months old), reproductive senescence stage (20 months old), and post-senescence stage (30 months old), respectively. With age, the thickness of the glomerular basement membrane (GBM) was increased. Notably, GBM knobs appeared at three months and became frequent with age. Using single-cell transcriptome data, we evaluated how various biological process appear in particular cell types and investigated the potential mechanism of formation of GBM konbs. In conclusion, having access to detailed kidney morphology and single-cell transcriptome maps from C57BL/6 mice at various developmental stages of C57BL/6 mice would be a novel and major resource for biological research and testing of prospective therapeutic approaches.

Abstract Background Lithuania, a Baltic country in the European Union, can be characterized by high alcohol consumption and attributable burden. The aim of this contribution is to estimate the mortality burden due to alcohol use for the past two decades based on different relative risk functions, identify trends, and analyse the associations of alcohol-attributable burden with alcohol control policies and life expectancy. Methods The standard methodology used by the World Health Organization for estimating alcohol-attributable mortality was employed to generate mortality rates for alcohol-attributable mortality, standardized for Lithuania’s 2021 population distribution. Joinpoint analysis, T-tests, correlations, and regression analyses including meta-regressions were used to describe trends and associations. Results Age-standardized alcohol-attributable mortality was high in Lithuania during the two decades between 2001 and 2021, irrespective of which relative risks were used for the estimates. Overall, there was a downward trend, mainly in males, which was associated with four years of intensive implementation of alcohol control policies in 2008, 2009, 2017, and 2018. For the remaining years, the rates of alcohol-attributable mortality were stagnant. Among males, the correlations between alcohol-attributable mortality and life expectancy were 0.90 and 0.76 for Russian and global relative risks respectively, and regression analyses indicated a significant association between changes in alcohol-attributable mortality and life expectancy, after controlling for gross domestic product. Conclusions Male mortality and life expectancy in Lithuania were closely linked to alcohol-attributable mortality and markedly associated with strong alcohol control policies. Further implementation of such policies is predicted to lead to further improvements in life expectancy.

Abstract Background The Baltic countries–Lithuania, Latvia and Estonia–are characterized by a high rate of fully alcohol-attributable mortality, compared with Poland. Alcohol control policy measures implemented since 2001 in the Baltic countries included a restriction on availability and an increase in excise taxation, among others. The aim of the current study was to evaluate the relationship between alcohol control policy implementation and alcohol-attributable mortality in the Baltic countries and Poland. Methods Alcohol-attributable mortality data for 2001–2020 was defined by codes 100% alcohol-attributable for persons aged 15 years and older in the Baltic countries and Poland. Alcohol control policies implemented between 2001 and 2020 were identified, and their impact on alcohol-attributable mortality was evaluated using an interrupted time-series methodology by employing a generalized additive model. Results Alcohol-attributable mortality was significantly higher in the Baltic countries, compared with Poland, for both males and females. In the final reduced model, alcohol control policy significantly reduced male alcohol-attributable mortality by 7.60% in the 12 months post-policy implementation. For females, the alcohol control policy mean-shift effect was higher, resulting in a significant reduction of alcohol-attributable mortality by 10.77% in the 12 months post-policy implementation. The interaction effects of countries and policy tested in the full model were not statistically significant, which indicated that the impact of alcohol control policy on alcohol-attributable mortality did not differ across countries for both males and females. Conclusions Based on the findings of the current study, alcohol control policy in the form of reduced availability and increased taxation was associated with a reduction in alcohol-attributable mortality among both males and females.

Abstract Background Periodontitis (PD) may affect temporomandibular joint disorders (TMD) and TMD may influence PD in previous observational studies. Nevertheless, these studies were prone to confounders and reverse causation, leading to incorrect conclusions about causality and direction of association. This research investigates the associations between PD and TMD employing bidirectional two-sample Mendelian randomization (MR) analysis. Methods Single-nucleotide polymorphisms (SNPs) related to PD (p

Abstract Background Ovarian cancer is one of the most lethal cancers in women because it is often diagnosed at an advanced stage. The molecular markers investigated thus far have been unsatisfactory. Methods We performed whole-exome sequencing on the human ovarian cancer cell lines 3AO and ES2 and the normal ovarian epithelial cell line IOSE-80. Molecular markers of ovarian cancer were screened from shared mutation genes and copy number variation genes in the 6q21-qter region. Results We found that missense mutations were the most common mutations in the gene (93%). The MUC12, FLG and MUC16 genes were highly mutated in 3AO and ES2 cells. Copy number amplification occurred mainly in 4p16.1 and 11q14.3, and copy number deletions occurred in 4q34.3 and 18p11.21. A total of 23 hub genes were screened, of which 16 were closely related to the survival of ovarian cancer patients. The three genes CCDC170, THBS2 and COL14A1 are most significantly correlated with the survival and prognosis of ovarian cancer. In particular, the overall survival of ovarian cancer patients with high CCDC170 gene expression was significantly prolonged (P

Abstract Background Taxation increases which reduce the affordability of alcohol are expected to reduce mortality inequalities. A recent taxation increase in Lithuania offers the unique possibility to test this hypothesis. Methods Census-linked mortality data between 2011 and 2019 were used to calculate monthly sex- and education-stratified age-standardized mortality rates for the population aged 40 to 70 years. As primary outcome, we analysed the difference in age-standardized all-cause mortality rates between the population of lowest versus highest educational achievement. The impact of the 2017 taxation increase was evaluated using interrupted time series analyses. To identify whether changes in alcohol use can explain the observed effects on all-cause mortality, the education-based mortality differences were then decomposed into n = 16 cause-of-death groupings. Results Between 2012 and 2019, education-based all-cause mortality inequalities in Lithuania declined by 18% among men and by 14% among women. Following the alcohol taxation increase, we found a pronounced yet temporary reduction of mortality inequalities among Lithuanian men (− 13%). Subsequent decomposition analyses suggest that the reduction in mortality inequalities between lower and higher educated men was mainly driven by narrowing mortality differences in injuries and infectious diseases. Conclusions A marked increase in alcohol excise taxation was associated with a decrease in mortality inequalities among Lithuanian men. More pronounced reductions in deaths from injuries and infectious diseases among lower as compared to higher educated groups could be the result of differential changes in alcohol use in these populations.

Abstract Background Despite being two Baltic countries with similar histories, Estonia and Lithuania have diverged in life expectancy trends in recent years. We investigated this divergence by comparing cause-specific mortality trends. Methods We obtained yearly mortality data for individuals 20 + years of age from 2001–2019 (19 years worth of data) through Statistics Lithuania, the Lithuanian Institute for Hygiene, and the National Institute for Health Development (Estonia). Using ICD-10 codes, we analyzed all-cause mortality rates and created eight major disease categories: ischemic heart disease, cerebrovascular disease, all other cardiovascular disease, cancers (neoplasms), digestive diseases, self-harm and interpersonal violence, unintentional injuries and related conditions, and other mortality (deaths per 100,000 population). We used joinpoint regression analysis, and analyzed the proportional contribution of each category to all-cause mortality. Results There was a steeper decline in all-cause mortality in Estonia (average annual percent change, AAPC = -2.55%, 95% CI: [-2.91%, -2.20%], P

Abstract Background A classic methodology used in evaluating the impact of health policy interventions is interrupted time-series (ITS) analysis, applying a quasi-experimental design that uses both pre- and post-policy data without randomization. In this paper, we took a simulation-based approach to estimating intervention effects under different assumptions. Methods Each of the simulated mortality rates contained a linear time trend, seasonality, autoregressive, and moving-average terms. The simulations of the policy effects involved three scenarios: 1) immediate-level change only, 2) immediate-level and slope change, and 3) lagged-level and slope change. The estimated effects and biases of these effects were examined via three matched generalized additive mixed models, each of which used two different approaches: 1) effects based on estimated coefficients (estimated approach), and 2) effects based on predictions from models (predicted approach). The robustness of these two approaches was further investigated assuming misspecification of the models. Results When one simulated dataset was analyzed with the matched model, the two analytical approaches produced similar estimates. However, when the models were misspecified, the number of deaths prevented, estimated using the predicted vs. estimated approaches, were very different, with the predicted approach yielding estimates closer to the real effect. The discrepancy was larger when the policy was applied early in the time-series. Conclusion Even when the sample size appears to be large enough, one should still be cautious when conducting ITS analyses, since the power also depends on when in the series the intervention occurs. In addition, the intervention lagged effect needs to be fully considered at the study design stage (i.e., when developing the models).

Abstract Background It remains unclear whether alcohol use disorders (AUDs) can be characterized by specific levels of average daily alcohol consumption. The aim of the current study was to model the distributions of average daily alcohol consumption among those who consume alcohol and those with alcohol dependence, the most severe AUD, using various clustering techniques. Methods Data from Wave 1 and Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions were used in the current analyses. Clustering algorithms were applied in order to group a set of data points that represent the average daily amount of alcohol consumed. Gaussian Mixture Models (GMMs) were then used to estimate the likelihood of a data point belonging to one of the mixture distributions. Individuals were assigned to the clusters which had the highest posterior probabilities from the GMMs, and their treatment utilization rate was examined for each of the clusters. Results Modeling alcohol consumption via clustering techniques was feasible. The clusters identified did not point to alcohol dependence as a separate cluster characterized by a higher level of alcohol consumption. Among both females and males with alcohol dependence, daily alcohol consumption was relatively low. Conclusions Overall, we found little evidence for clusters of people with the same drinking distribution, which could be characterized as clinically relevant for people with alcohol use disorders as currently defined.

Abstract Background The progression of coagulation in COVID-19 patients with confirmed discharge status and the combination of autopsy with complete hemostasis parameters have not been well studied. Objective To clarify the thrombotic phenomena and hemostasis state in COVID-19 patients based on epidemiological statistics combining autopsy and statistical analysis. Methods Using autopsy results from 9 patients with COVID-19 pneumonia and the medical records of 407 patients, including 39 deceased patients whose discharge status was certain, time-sequential changes in 11 relevant indices within mild, severe and critical infection throughout hospitalization according to the Chinese National Health Commission (NHC) guidelines were evaluated. Statistical tools were applied to calculate the importance of 11 indices and the correlation between those indices and the severity of COVID-19. Results At the beginning of hospitalization, platelet (PLT) counts were significantly reduced in critically ill patients compared with severely or mildly ill patients. Blood glucose (GLU), prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer levels in critical patients were increased compared with mild and severe patients during the entire admission period. The International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) score was also high in critical patients. In the relatively late stage of nonsurvivors, the temporal changes in PLT count, PT, and D-dimer levels were significantly different from those in survivors. A random forest model indicated that the most important feature was PT followed by D-dimer, indicating their positive associations with disease severity. Autopsy of deceased patients fulfilling diagnostic criteria for DIC revealed microthromboses in multiple organs. Conclusions Combining autopsy data, time-sequential changes and statistical methods to explore hemostasis-relevant indices among the different severities of the disease helps guide therapy and detect prognosis in COVID-19 infection.

Abstract Background Tyrosine kinase receptor erythropoietin-producing hepatocellular receptor A2 (EphA2) is abundant in the endometrium and plays a role in the establishment of eutopic implantation. A similar molecular mechanism may exist between uterine implantation and tubal implantation, therefore EphA2 involvement in tubal pregnancy is suspected. Due to the limited availability of human Fallopian tube specimens, EphA2 expression in human Fallopian tube epithelium remains largely unknown. Methods A total of 31 women with tubal pregnancy and 41 non-pregnant women with benign uterine diseases were enrolled in this study. Immunohistochemistry was used to investigate the expression pattern of EphA2 in the Fallopian tube epithelium of non-pregnant women (n = 29) and women with tubal pregnancy (n = 17). The changes of EphA2 and its activated form, phosphorylated-EphA2 (Pho-EphA2), in the Fallopian tube epithelium from non-pregnant women (n = 12) and women with tubal pregnancy (n = 14) were compared by quantitative RT-PCR and western blot assay. Results EphA2 was expressed throughout the Fallopian tube epithelium, including the isthmus, the ampulla and the infundibulum. EphA2 concentration remained unchanged throughout the whole menstrual cycle, irrespective of menstrual phases and tubal regions. EphA2 mRNA in the Fallopian tube epithelium did not differ between normal women and women with tubal pregnancy (P > 0.05). With respect to the protein level, a significantly higher ratio of EphA2 over Pho-EphA2 was shown in women with tubal pregnancy (P

Abstract Background Chronic inflammation is deemed to play a significant effect on initiation and progression of esophageal squamous cell carcinoma (ESCC). In current study, we investigated the prognostic and predictive role of albumin (Alb) to fibrinogen (Fib) ratio (AFR) and a novel AFR–Alb-derived neutrophil/lymphocyte ratio (dNLR) score (ADS) in ESCC patients undergoing esophagectomy and compared them with Fib, Alb, neutrophil to lymphocyte ratio (NLR), dNLR, platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR). Materials and methods A total of 153 clinical confirmed ESCC patients undergoing esophagectomy between January 2011 and December 2013 were included in present study. We detected preoperative Alb, Fib and neutrophil, monocyte, lymphocyte and platelet count, and obtained overall survival (OS) by 3 years’ follow-up in the cases. X-tile software, Kaplan–Meier curve, Cox regression and predicted nomogram were used to evaluate the predictive and prognostic role of them in ESCC patients. Results The optimal cut-off values of Fib, Alb, AFR, NLR, dNLR, PLR and LMR were 3.2 mg/dL, 38.2 g/L, 9.3, 2.1, 4.3, 145.9 and 2.3, respectively. High levels of Fib [(adjusted hazard ratio (HR) = 2.148, 95% confidential interval (CI) (1.229–3.753)], dNLR (adjusted HR = 2.338, 95% CI 1.626–5.308) and PLR (adjusted HR = 1.964, 95% CI 1.129–3.415) as well as low AFR (adjusted HR = 2.381, 95% CI 1.152–4.926) and Alb (adjusted HR = 2.398, 95% CI 1.342–4.273) were significantly associated with decreased OS in ESCC patients. The survival predictive areas under the time-dependent receiver operating characteristics curve of AFR, dNLR and Alb were higher than Fib and PLR, respectively. High ADS score was significantly associated with short 3 years’ OS of ESCC patients (adjusted HR = 2.94, 95% CI 1.70–5.08). Moreover, OS of ESCC patients receiving adjuvant radio-chemotherapy was longer than those without the treatment in high ADS score subgroup (p = 0.001), however, no significant survival difference was observed in the patients with or without treatment radio-chemotherapy (p = 0.297). Additionally, a significant difference was observed in c-index values of the nomograms including or without ADS (0.720 vs. 0.670, p