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Summary: Obstructive sleep apnea (OSA) has been linked to cancer in several clinical and community‐based cohorts. The effect in community‐based studies free of clinical referral bias needs to be replicated. In this observational prospective cohort study, we pooled data from three community‐based prospective cohorts (Uppsala Sleep and Health in Men cohort [UMEN]; Sleep and health in women [SHE]; Men Androgen Inflammation Lifestyle Environment and Stress Cohort [MAILES]; nTotal = 1467). All cohorts had objective data on obstructive sleep apnea and registry linkage data on cancer and cancer mortality. Analyses for different obstructive sleep apnea measures (apnea–hypopnea index [AHI], oxygen desaturation index [ODI], and minimal saturation) as risk factors for cancer incidence (all cancers) were performed using Cox proportional hazards models (follow‐up 5–16 years). We did not find an overall increased risk of cancer after adjustment for age, sex, and BMI (HRAHI [95% CI] = 1.00 [0.98; 1.01] and HRODI [95% CI] = 0.99 [0.97; 1.01]). Stratifying by daytime sleepiness did not influence the association. Cancer mortality was not significantly associated with obstructive sleep apnea. Taken together, we did not observe an overall increased risk of cancer or cancer mortality in relation to obstructive sleep apnea, however, our confidence limits remain wide for important diagnostic categories of sleep apnea severity. The relationship between obstructive sleep apnea and cancer needs further investigation in a comprehensive multi‐cohort approach with greater statistical precision. For future studies we may need to find and then combine every community‐based cohort study that can provide a definitive answer to the question on the risk of cancer from obstructive sleep apnea in the general population. [ABSTRACT FROM AUTHOR]

Chronic inflammation and excessive reactive oxygen species (ROS) can impair diabetic wound healing. Regulatory T cells (Tregs) have emerged as a promising target to promote wound healing by regulating the immune system and supporting tissue repair through the secretion of growth factors and cytokines. However, an effective strategy for the on‐demand recruitment of Tregs for wound healing is still lacking. Here, an ROS‐scavenging Tregs‐recruiting hydrogel patch is developed for the sequential release of C─C motif chemokine 22 (CCL22) triggered by the ROS in the diabetic wound bed. The hydrogel patch is prepared by crosslinking the gelatin with ROS cleavable linker together with CCL22 (RSG‐CCL22). RSG‐CCL22 presented desirable physical properties suitable for skin regeneration purposes. In addition, the ROS scavenging feature of the RSG suppresses the differentiation of T helper 17 (Th17) cells and protects the recruited Tregs from apoptosis and oxidative stress, which maximizes their function in accelerating wound closure and promoting hair follicle regeneration in a diabetic full‐thickness skin defect mouse model. Therefore, the proposed approach provides a new therapeutic strategy for tissue regeneration and wound repair via effective recruitment of functional Tregs through ROS‐triggered on‐demand delivery. [ABSTRACT FROM AUTHOR]

Rationale: Postbronchodilator spirometry is used for the diagnosis of chronic obstructive pulmonary disease. However, prebronchodilator reference values are used for spirometry interpretation. Objectives: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using preor postbronchodilator reference values generated within SCAPIS (Swedish CArdioPulmonary bioImage Study) when interpreting postbronchodilator spirometry in a general population. Methods: SCAPIS reference values for postbronchodilator and prebronchodilator spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or postbronchodilator reference values, with respiratory burden in the SCAPIS general population (28,851 individuals). Measurements and Main Results: Bronchodilation resulted in higher predicted medians and lower limits of normal (LLNs) for FEV1/FVC ratios. The prevalence of postbronchodilator FEV1/FVC ratio lower than the prebronchodilator LLN was 4.8%, and that of postbronchodilator FEV1/FVC lower than the postbronchodilator LLN was 9.9%, for the general population. An additional 5.1% were identified as having an abnormal postbronchodilator FEV1/FVC ratio, and this group hadmore respiratory symptoms, emphysema (13.5% vs. 4.1%; P,0.001), and self-reported physician-diagnosed chronic obstructive pulmonary disease (2.8% vs. 0.5%, P,0.001) than subjects with a postbronchodilator FEV1/FVC ratio greater than the LLN for both pre- and postbronchodilation. Conclusions: Pre- and postbronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of postbronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using postbronchodilator reference values when interpreting postbronchodilator spirometry might enable the identification of individuals with mild disease and be clinically relevant. [ABSTRACT FROM AUTHOR]

Background/aim: This study aimed to distinguish different phenotypes of long COVID through the post-COVID syndrome (PCS) score based on long-term persistent symptoms following COVID-19 and evaluate whether these symptoms affect general health and work ability. In addition, the study identified predictors for severe long COVID. Method: This cluster analysis included cross-sectional data from three cohorts of patients after COVID-19: non-hospitalized (n = 401), hospitalized (n = 98) and those enrolled at the post-COVID outpatient's clinic (n = 85). All the subjects responded to the survey on persistent long-term symptoms and sociodemographic and clinical factors. K-Means cluster analysis and ordinal logistic regression were used to create PCS scores that were used to distinguish patients' phenotypes. Results: 506 patients with complete data on persistent symptoms were divided into three distinct phenotypes: none/mild (59%), moderate (22%) and severe (19%). The patients with severe phenotype, with the predominating symptoms were fatigue, cognitive impairment and depression, had the most reduced general health status and work ability. Smoking, snuff, body mass index (BMI), diabetes, chronic pain and symptom severity at COVID-19 onset were factors predicting severe phenotype. Conclusion: This study suggested three phenotypes of long COVID, where the most severe was associated with the highest impact on general health status and working ability. This knowledge on long COVID phenotypes could be used by clinicians to support their medical decisions regarding prioritizing and more detailed follow-up of some patient groups. [ABSTRACT FROM AUTHOR]

Background: Allergic disease is common. The aim of this study was to look at the change in asthma and rhinitis over time and to characterise factors contributing to remission and persistence of disease. Methods: This cohort study included 255 individuals with or without asthma and or rhinitis that participated in a population survey and a follow‐up 10 years later. The participants were tested for allergic sensitisation, total IgE, multiplex allergen component analysis and type‐2 inflammatory markers: exhaled nitric oxide (FENO), eosinophil cationic protein (ECP) and eosinophil‐derived neurotoxin (EDN). Results: Of the 132 healthy individuals, 112 remained healthy, 16 developed rhinitis, 4 asthma and rhinitis over the 10 years. Out of 82 subjects with rhinitis, 26 went into remission, 53 remained unchanged and 3 developed asthma in addition to rhinitis. None of the 41 participants with asthma and rhinitis went into remission. Subjects with persistent rhinitis and asthma had higher levels of total IgE (odds ratio [OR] 95% confidence interval [CI]: 6.16 [3.05–12.5]) at baseline and after 10 years, and FENO and ECP at baseline (OR per log unit increase, 95% CI 5.21 [1.20–22.7] and 6.32 [1.52–26.4], respectively), compared with those that remained healthy. Subjects with persistent rhinitis were more likely to be sensitised to grass pollen and had higher total IgE levels than those that went into remission. Individuals with persistent asthma were more likely to be sensitised to tree pollen and furry animals than those with only persistent rhinitis (OR 95% CI: 3.50 [1.29–9.49] and 6.73 [2.00–22.6], respectively). Conclusion: IgE sensitisation and total IgE levels are associated with the persistence of rhinitis and asthma. Participants with persistent allergic disease had higher levels of allergen sensitisation and type 2 inflammation markers at baseline than those who remained healthy. [ABSTRACT FROM AUTHOR]

This study presents a separable nonlinear least squares (SNLLS) implementation of the minimum distance (MD) estimator employing a fixed-weight matrix for estimating structural equation models (SEMs). In contrast to the standard implementation of the MD estimator, in which the complete set of parameters is estimated using nonlinear optimization, the SNLLS implementation allows a subset of parameters to be estimated using (linear) least squares (LS). The SNLLS implementation possesses a number of benefits, such as faster convergence, better performance in ill-conditioned estimation problems, and fewer required starting values. The present work demonstrates that SNLLS, when applied to SEM estimation problems, significantly reduces the estimation time. Reduced estimation time makes SNLLS particularly useful in applications involving some form of resampling, such as simulation and bootstrapping. [ABSTRACT FROM AUTHOR]

For example, the Vogel data set included a large proportion of smokers, Newbury included past smokers, whereas the Schulz and SCAPIS reference groups were all never-smokers. Of these, 1,066 individuals were lung healthy, never-smoking and BMI <30, and hence included in the reference population used for defining the limits of normality in the SCAPIS material. Existing reference values for IOS measurements were examined in Swedish healthy, non-smoking individuals. [Extracted from the article]

Minimally invasive treatment via injectable delivery of cells has drawn extensive attention for tissue regeneration because it reduces the need for substantial open surgery and fits tissue defects with complex shapes, making it a suitable option for repairing articular cartilage defects. This work presents an alkaline treatment method to fabricate open‐porous poly (lactic‐co‐glycolic acid) microspheres (OPMs) as bone marrow stromal cells (BMSCs) carriers for cartilage regeneration. OPMs have better biodegradation property and the extended pores can provide easier access for cells to the internal space. The BMSCs cultured with OPMs can display enhanced cell proliferation, up‐regulated expression of cartilage‐related mRNAs and proteins, and improved cartilage regeneration in vitro and in vivo. These results highlight the advantage and potential of using OPMs fabricated via simple alkaline treatment as injectable stem cell carriers for cartilage regeneration through minimally invasive procedures. [ABSTRACT FROM AUTHOR]

Animal models and traditional cell cultures are essential tools for drug development. However, these platforms can show striking discrepancies in efficacy and side effects when compared to human trials. These differences can lengthen the drug development process and even lead to drug withdrawal from the market. The establishment of preclinical drug screening platforms that have higher relevancy to physiological conditions is desirable to facilitate drug development. Here, a heart‐on‐a‐chip platform, incorporating microgrooves and electrical pulse stimulations to recapitulate the well‐aligned structure and synchronous beating of cardiomyocytes (CMs) for drug screening, is reported. Each chip is made with facile lithographic and laser‐cutting processes that can be easily scaled up to high‐throughput format. The maturation and phenotypic changes of CMs cultured on the heart‐on‐a‐chip is validated and it can be treated with various drugs to evaluate cardiotoxicity and cardioprotective efficacy. The heart‐on‐a‐chip can provide a high‐throughput drug screening platform in preclinical drug development. [ABSTRACT FROM AUTHOR]

Immunotherapy is a class of promising anticancer treatments that has recently gained attention due to surging numbers of FDA approvals and extensive preclinical studies demonstrating efficacy. Nevertheless, further clinical implementation has been limited by high variability in patient response to different immunotherapeutic agents. These treatments currently do not have reliable predictors of efficacy and may lead to side effects. The future development of additional immunotherapy options and the prediction of patient‐specific response to treatment require advanced screening platforms associated with accurate and rapid data interpretation. Advanced engineering approaches ranging from sequencing and gene editing, to tumor organoids engineering, bioprinted tissues, and organs‐on‐a‐chip systems facilitate the screening of cancer immunotherapies by recreating the intrinsic and extrinsic features of a tumor and its microenvironment. High‐throughput platform development and progress in artificial intelligence can also improve the efficiency and accuracy of screening methods. Here, these engineering approaches in screening cancer immunotherapies are highlighted, and a discussion of the future perspectives and challenges associated with these emerging fields to further advance the clinical use of state‐of‐the‐art cancer immunotherapies are provided. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have been widely used for regenerative therapy. In most current clinical applications, MSCs are delivered by injection but face significant issues with cell viability and penetration into the target tissue due to a limited migration capacity. Some therapies have attempted to improve MSC stability by their encapsulation within biomaterials; however, these treatments still require an enormous number of cells to achieve therapeutic efficacy due to low efficiency. Additionally, while local injection allows for targeted delivery, injections with conventional syringes are highly invasive. Due to the challenges associated with stem cell delivery, a local and minimally invasive approach with high efficiency and improved cell viability is highly desired. In this study, a detachable hybrid microneedle depot (d‐HMND) for cell delivery is presented. The system consists of an array of microneedles with an outer poly(lactic‐co‐glycolic) acid shell and an internal gelatin methacryloyl (GelMA)‐MSC mixture (GMM). The GMM is characterized and optimized for cell viability and mechanical strength of the d‐HMND required to penetrate mouse skin tissue is also determined. MSC viability and function within the d‐HMND is characterized in vitro and the regenerative efficacy of the d‐HMND is demonstrated in vivo using a mouse skin wound model. [ABSTRACT FROM AUTHOR]

Background: Examining body mass index (BMI) change over life course is crucial for cardiovascular health promotion and prevention. So far, there is very few evidence on the long-term change of BMI from childhood to late life. This study aimed to examine the life-course trajectory patterns of BMI and then to link the trajectory patterns to cardiovascular risk factors in adulthood. Methods: Based on longitudinal data from the China Health and Nutrition Survey, 5276 participants (aged 6–60) at baseline (in 1989) with up to 7 measurements of BMI during 1989–2009 were selected in this study. Cardiovascular risk factors including high blood pressure, high blood glucose and high blood lipids were assessed in 2411 participants in 2009. Latent growth curve modelling was used to analyse the BMI trajectories, and logistic regression was used to examine the associations between trajectory patterns and cardiovascular risk factors. Results: Four trajectories patterns of BMI over life course (age 6–80) were identified: Normal-Stable (22.4% of the total participants), Low normal-Normal-Stable (44.1%), Low normal-Normal-Overweight (27.2%), and Overweight-Obese (4.3%). Compared to those with Normal-Stable pattern, those with Low normal-Normal-Stable pattern, Low normal-Normal-Overweight pattern and Overweight-Obese pattern had higher risk of high blood pressure (odds ratio range = 1.6–6.6), high blood glucose (1.7–9.1), dyslipidemia (2.6–5.9) and having at least two of the three cardiovascular risk factors (3.9–30.9). Conclusions: Having a stable BMI within normal range over life course is associated with the lowest cardiovascular risk, whereas remaining overweight and obese over life course is associated with the highest cardiovascular risk. [ABSTRACT FROM AUTHOR]

We consider an exact factor model with integrated factors and propose an LM-type test for unit roots in the idiosyncratic component. We show that, for a fixed number of panel individuals (N) and when the number of time points (T) tends to infinity, the limiting distribution of the LM-type statistic is a weighted sum of independent Chi-square variables with one degree of freedom, and whenTtends to infinity followed byNtending to infinity, the limiting distribution is standard normal. The results should contribute to the challenging task of deriving likelihood-based unit-root tests in dynamic factor models. [ABSTRACT FROM AUTHOR]

In this article, an exact factor model is considered, and a Lagrange multiplier-type test is derived for a homogeneous unit root in the idiosyncratic component. It is shown that under sequential asymptotics, its null limiting distribution is standard normal, regardless of whether the factors are integrated, cointegrated or stationary. In a simulation study, the size and local power of the Lagrange multiplier-type test and some popular non-likelihood-based tests are compared. The simulation results show that the Lagrange multiplier-type test has the highest local power as the panel dimensions tend to infinity, with the actual size tending to the nominal size. [ABSTRACT FROM AUTHOR]

The cover image is based on the Research Article Injectable Open‐porous PLGA Microspheres as Cell Carriers for Cartilage Regeneration by Songsong Zhu et al., https://doi.org/10.1002/jbm.a.37196. [ABSTRACT FROM AUTHOR]

[Display omitted] Cancer remains a leading health burden worldwide. One of the challenges hindering cancer therapy development is the substantial discrepancies between the existing cancer models and the tumor microenvironment (TME) of human patients. Constructing tumor organoids represents an emerging approach to recapitulate the pathophysiological features of the TME in vitro. Over the past decade, various approaches have been demonstrated to engineer tumor organoids as in vitro cancer models, such as incorporating multiple cellular populations, reconstructing biophysical and chemical traits, and even recapitulating structural features. In this review, we focus on engineering approaches for building tumor organoids, including biomaterial-based, microfabrication-assisted, and synthetic biology-facilitated strategies. Furthermore, we summarize the applications of engineered tumor organoids in basic cancer research, cancer drug discovery, and personalized medicine. We also discuss the challenges and future opportunities in using tumor organoids for broader applications. [ABSTRACT FROM AUTHOR]