bluuebunny/crossref_metadata_2025 huggingface dataset:
FRESH bioprinting technology for tissue engineering – the influence of printing process and bioink composition on cell behavior and vascularization
Authors: Kreimendahl Franziska , Kniebs Caroline , Tavares Sobreiro Ana Margarida , Schmitz-Rode Thomas , Jockenhoevel Stefan , Thiebes Anja Lena
Published: July 2021

The rapid and tailored biofabrication of natural materials is of high interest for the field of tissue engineering and regenerative medicine. Scaffolds require both high biocompatibility and tissue-dependent mechanical strength to function as basis for tissue-engineered implants. Thus, natural hydrogels such as fibrin are promising but their rapid biofabrication remains challenging. Printing of low viscosity and slow polymerizing solutions with good spatial resolution can be achieved by freeform reversible embedding of suspended hydrogels (FRESH) bioprinting of cell-laden natural hydrogels. In this study, fibrin and hyaluronic acid were used as single components as well as blended ink mixtures for the FRESH bioprinting. Rheometry revealed that single materials were less viscous than the blended bioink showing higher values for viscosity over a shear rate of 10–1000 s−1. While fibrin showed viscosities between 0.1624 and 0.0017 Pa·s, the blended ink containing fibrin and hyaluronic acid were found to be in a range of 0.1–1 Pa·s. In 3D vascularization assays, formation of vascular structures within the printed constructs was investigated indicating that the printing process did not harm cells and allowed formation of vasculature comparable to moulded control samples. Best values for vascularization were achieved in bioinks consisting of 1.0% fibrin-0.5% hyaluronic acid. The vascular structure area and length were three times higher compared to other tested bioinks, and structure volume as well as number of branches revealed almost four times higher values. In this study, we combined the benefits of the FRESH printing technique with in vitro vascularization, showing that it is possible to achieve a mechanically stable small-scale hydrogel construct incorporating vascular network formation.
Toward the commoning of governance
Authors: Leitheiser Stephen , Trell Elen-Maarja , Horlings Ina , Franklin Alex
Published: July 2021

Conventional political thought and practice continue to be stifled by a dilemma of choosing between the ideal imaginaries of State and/or Market solutions. Widely presupposed as the only valid possibilities in both theory and practice, this stale dilemma covers up a real multitude of actually existing alternative approaches to governance practiced in civil society. State/Market approaches are identical in the way that they construct a ‘spectator’ role for communities, who are left to choose between their preferred set of rules and norms developed elsewhere. The concept of commoning governance offers an opportunity to break free of this stalemate. It creates a new role for citizens and their communities as ‘sparring partners’; who although they operate within the limits of current State/Market institutions, create new norms and rules against and beyond them. In the paper, we first expand on our understanding of commoning governance: re-designing governance arrangements to serve the common good. That is here understood in terms of (radical) democracy, solidarity and sustainable ecological relationships. Second, we illustrate how commoning efforts on the ground contribute to the reclaiming of the democratic imaginary as a political arena by zooming in to a case study of the three cities involved in civic-led network of German Food Policy Councils. Finally, we reflect on the empirical barriers that communities of commoning endure, and call on policymakers, planners and scholars to interrogate their own normative understandings of citizenship and democracy, and begin to recognize theoretical and latent possibilities by enabling commoning with new or re-designed institutions of governance.
Revisiting Union: A New Perspective on an Old Outcome
Authors: Looney Austin M. , Day Jonathan
Published: July 2021

Background:

To present the inherent and unique challenges associated with utilizing fracture healing as an outcome measure in foot and ankle orthopedics, specifically the statistical methods used in assessing time to union.

Methods:

In a previously published manuscript assessing the effect of delayed weightbearing on time to union following intramedullary (IM) screw fixation of Jones (Zone 2 fifth metatarsal base) fractures, patients were divided into early weightbearing (EWB, n=20) and delayed weightbearing (DWB, n=21) cohorts (within or beyond 2 weeks, respectively). Time to union was determined and compared between the 2 cohorts using cumulative link model analysis, with delayed union (12.5 weeks) defined from established literature.

Results:

Cumulative link model analysis demonstrated no significant differences in time to union (EWB: 25% by 6th week, 55% by 12th week; DWB: 33% by 6th week, 43% by 12th week; P = .819) or delayed unions (EWB, 20% vs DWB, 24%; P > .999).

Conclusion:

Our analysis using cumulative link models, or ordinal regression, in the statistical analysis of time to union, determined that that early weightbearing following IM screw fixation in Jones fractures appeared to be safe without delaying fracture healing. This statistical approach can be considered when describing a continuous outcome captured by infrequent observations.
The Use of the Comma Sign and Tissue for Recognition, Reduction, and Stability During Arthroscopic Repair of Combined Anterosuperior Cuff Tears
Authors: Corbaz Jocelyn , Blakeney William G. , Athwal George , Bauer Stefan
Published: July 2021

Background:

The comma sign is a useful marker for combined retracted supraspinatus and subscapularis tears. It was first described by the group of Burkhart as a “composite ligamentous structure” of the rotator interval attached to the retracted subscapularis. However, Neyton and coworkers suggested that the ruptured superior part of subscapularis is pulled upward by supraspinatus retraction. This video illustrates the value of “comma” recognition for reduction and repair stability. We feel that the comma tissue can be a composition of rotator interval ligaments with or without superior subscapularis contribution depending on an associated cleavage tear.

Indications:

Patients with retracted anterosuperior tears, unless muscle quality is poor (Goutallier classification ≥3). Understanding of the comma tissue is difficult but of crucial importance to assess complex anterosuperior cuff tears for reduction and repair with stability by maintaining and integrating this comma link into the repair construct.

Technique Description:

Arthroscopic setup includes beach chair position, armholder, cerebral saturation monitoring (target mean arterial blood pressure of about 70 mm Hg). Previously described circumferential portals were used for a repair with a double row construct (4 medial anchors: 2.5 for subscapularis; 1.5 for supraspinatus) and 2 lateral anchors. The superior boarder of subscapularis as well as the retracted capsular layer of supraspinatus was reduced and fixed using a lasso loop technique. Key stages are (1) tendon manipulation with 2 traction sutures; (2) tendon release; (3) comma reduction; (4) footprint preparation (burr, microfracture); (5) retrograde suture passing; (6) knot tying, knotless lateral row; and (7) a close surgeon to physiotherapist rehabilitation link (6 weeks passive to 90°, no resistance training for 3-6 months).

Results:

Senior author’s (S.B.) series: 32 anterosuperior tears over 4 years (mean age: 62 years, 48-73 years), minimum follow-up 1 year showed good results (mean SSV: 85% [preop. 35%], range: 40%-95%; mean Constant: 82 [preop. 30], range: 40-90). One major complication (cutibacterium infection; brick layer; workers compensation; invalidity demand; Constant/Subjective Shoulder Value both 40) and minor temporary stiffness at 3 months (8 patients; 22%).

Conclusion:

Adequate reduction and comma integration into a solid repair construct, as well as responsible rehabilitation surveillance, deliver successful results after technically intricate anterosuperior repairs.
Pro: Access to advanced therapies for severe asthma should be restricted to patients with satisfactory adherence to maintenance treatment
Authors: Murphy Anna C. , Boddy Claire , Bradding Peter
Published: July 2021

Inhaled corticosteroids (ICS) are the core component of asthma treatment and the only maintenance therapy known to prevent asthma death. There is currently no evidence that biologics prevent asthma death in people with asthma, and as such, biologics cannot be recommended as an alternative to ICS therapy. Taking the time to assess adherence and provide interventions and education to support patients in asthma self-management has been shown to improve patient outcomes. It is therefore our responsibility as healthcare professionals to ensure that patients are supported, educated and motivated to adhere to ICS therapy before progressing to biologic therapies.
Danshensu inhibits the IL-1β-induced inflammatory response in chondrocytes and osteoarthritis possibly via suppressing NF-κB signaling pathway
Authors: Xu Zhixian , Ke Tie , Zhang Yongfa , Guo Licheng , Chen Feng , He Wubing
Published: July 2021

Purpose

Osteoarthritis (OA) is the most common inflammatory disease associated with pain and cartilage destruction. Interleukin (IL)-1β is widely used to induce inflammatory response in OA models. This study aimed to explore the role of Danshensu (DSS) in IL-1β-induced inflammatory responses in OA.

Methods

IL-1β was used to induce chondrocyte inflammation. Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay. IL-6, COX-2, TNF-α, and iNOS mRNA levels were detected by qRT-PCR. MMP3, MMP13, ADAMTS4, ADAMTS5, Aggrecan, Collagen, p-IκBα, and p-p65 protein levels were detected by Western blot. An OA mouse model was established by surgical destabilization of the medial meniscus (DMM), and the Osteoarthritis Research Society International (OARSI) score was evaluated by H&E staining.

Results

DSS did not affect the levels of inflammatory indicators including IL-6, COX-2, TNF-α, iNOS, PEG2, and NO but suppressed COX-2 and iNOS protein expression in IL-1β treated chondrocytes. In addition, DSS downregulated IL-1β-enhanced expression of MMP3, MMP13, ADAMTS4, and ADAMTS5 and upregulated aggrecan and collagen expression. Moreover, DSS significantly inhibited IL-1β-induced phosphorylation of p-IκBα and p-p65 in a dose-dependent manner in chondrocytes, suggesting it plays a role in the NF-κB signaling pathway. Furthermore, DSS significantly reduced DMM-induced cartilage OARSI score in mice, further demonstrating its protective role in OA progression in vivo.

Conclusions

Our study revealed the protective role of DSS in OA, suggesting that DSS might act as a potential treatment for OA.
Deep Learning Based Data Fusion for Sensor Fault Diagnosis and Tolerance in Autonomous Vehicles
Authors: Pan Huihui , Sun Weichao , Sun Qiming , Gao Huijun
Published: July 2021

Environmental perception is one of the key technologies to realize autonomous vehicles. Autonomous vehicles are often equipped with multiple sensors to form a multi-source environmental perception system. Those sensors are very sensitive to light or background conditions, which will introduce a variety of global and local fault signals that bring great safety risks to autonomous driving system during long-term running. In this paper, a real-time data fusion network with fault diagnosis and fault tolerance mechanism is designed. By introducing prior features to realize the lightweight network, the features of the input data can be extracted in real time. A new sensor reliability evaluation method is proposed by calculating the global and local confidence of sensors. Through the temporal and spatial correlation between sensor data, the sensor redundancy is utilized to diagnose the local and global confidence level of sensor data in real time, eliminate the fault data, and ensure the accuracy and reliability of data fusion. Experiments show that the network achieves state-of-the-art results in speed and accuracy, and can accurately detect the location of the target when some sensors are out of focus or out of order. The fusion framework proposed in this paper is proved to be effective for intelligent vehicles in terms of real-time performance and reliability.
Sequence-based genome-wide association study of individual milk mid-infrared wavenumbers in mixed-breed dairy cattle
Authors: Tiplady Kathryn M. , Lopdell Thomas J. , Reynolds Edwardo , Sherlock Richard G. , Keehan Michael , Johnson Thomas JJ. , Pryce Jennie E. , Davis Stephen R. , Spelman Richard J. , Harris Bevin L. , Garrick Dorian J. , Littlejohn Mathew D.
Published: July 2021

Background

Fourier-transform mid-infrared (FT-MIR) spectroscopy provides a high-throughput and inexpensive method for predicting milk composition and other novel traits from milk samples. While there have been many genome-wide association studies (GWAS) conducted on FT-MIR predicted traits, there have been few GWAS for individual FT-MIR wavenumbers. Using imputed whole-genome sequence for 38,085 mixed-breed New Zealand dairy cattle, we conducted GWAS on 895 individual FT-MIR wavenumber phenotypes, and assessed the value of these direct phenotypes for identifying candidate causal genes and variants, and improving our understanding of the physico-chemical properties of milk.

Results

Separate GWAS conducted for each of 895 individual FT-MIR wavenumber phenotypes, identified 450 1-Mbp genomic regions with significant FT-MIR wavenumber QTL, compared to 246 1-Mbp genomic regions with QTL identified for FT-MIR predicted milk composition traits. Use of mammary RNA-seq data and gene annotation information identified 38 co-localized and co-segregating expression QTL (eQTL), and 31 protein-sequence mutations for FT-MIR wavenumber phenotypes, the latter including a null mutation in the ABO gene that has a potential role in changing milk oligosaccharide profiles. For the candidate causative genes implicated in these analyses, we examined the strength of association between relevant loci and each wavenumber across the mid-infrared spectrum. This revealed shared association patterns for groups of genomically-distant loci, highlighting clusters of loci linked through their biological roles in lactation and their presumed impacts on the chemical composition of milk.

Conclusions

This study demonstrates the utility of FT-MIR wavenumber phenotypes for improving our understanding of milk composition, presenting a larger number of QTL and putative causative genes and variants than found from FT-MIR predicted composition traits. Examining patterns of significance across the mid-infrared spectrum for loci of interest further highlighted commonalities of association, which likely reflects the physico-chemical properties of milk constituents.
Antimicrobial resistance in patients with decompensated liver cirrhosis and bacterial infections in a tertiary center in Northern Germany
Authors: Hillert Annika , Schultalbers Marie , Tergast Tammo L. , Vonberg Ralf-Peter , Rademacher Jessica , Wedemeyer Heiner , Cornberg Markus , Ziesing Stefan , Maasoumy Benjamin , Höner zu Siederdissen Christoph
Published: July 2021

Background and aims

Bacterial infections are common in patients with decompensated liver cirrhosis and a leading cause of death. Reliable data on antibiotic resistance are required to initiate effective empiric therapy. We here aim to assess the antimicrobial resistance profile of bacteria among patients with liver cirrhosis and infection.

Methods

Overall, 666 cirrhotic patients admitted to Hannover Medical School between January 2012 and April 2018 with ascites were assessed for bacterial infection. In case of infection, bacteria cultured from microbiological specimens of ascites, blood or urine were identified and analyzed for resistances against common antibiotic agents. Furthermore, analyses compared two periods of time and community-acquired vs. nosocomial infections.

Results

In 281 patients with infection, microbiological sampling was performed and culture-positive results were obtained in 56.9%. Multidrug-resistant (MDR)-bacteria were found in 54 patients (19.2%). Gram-positive organisms were more common (n = 141/261, 54.0%) and detected in 116/192 culture-positive infections (60.4%). Comparing infections before and after 2015, a numerical decline for MDR-bacteria (23.8% vs. 15.6%, p = 0.08) was observed with a significant decline in meropenem resistance (34.9% vs. 19.5%, p = 0.03). MDR-bacteria were more frequent in the case of nosocomial infections. Of note, in ascites the majority of the tested bacteria were resistant against ceftriaxone (73.8%) whereas significantly less were resistant against meropenem (27.0%) and vancomycin (25.9%).

Conclusions

In our tertiary center, distinct ratios of gram-positive infection with overall low ratios of MDR-bacteria were found. Adequate gram-positive coverage in the empiric therapy should be considered. Carbapenem treatment may be omitted even in nosocomial infection. In contrast, 3rd generation cephalosporins cannot be recommended even in community-acquired infection in our cirrhotic population.
The effectiveness of syndromic surveillance for the early detection of waterborne outbreaks: a systematic review
Authors: Hyllestad Susanne , Amato Ettore , Nygård Karin , Vold Line , Aavitsland Preben
Published: July 2021

Background

Waterborne outbreaks are still a risk in high-income countries, and their early detection is crucial to limit their societal consequences. Although syndromic surveillance is widely used for the purpose of detecting outbreaks days earlier than traditional surveillance systems, evidence of the effectiveness of such systems is lacking. Thus, our objective was to conduct a systematic review of the effectiveness of syndromic surveillance to detect waterborne outbreaks.

Method

We searched the Cochrane Library, Medline/PubMed, EMBASE, Scopus, and Web of Science for relevant published articles using a combination of the keywords ‘drinking water’, ‘surveillance’, and ‘waterborne disease’ for the period of 1990 to 2018. The references lists of the identified articles for full-text record assessment were screened, and searches in Google Scholar using the same key words were conducted. We assessed the risk of bias in the included articles using the ROBINS-I tool and PRECEPT for the cumulative body of evidence.

Results

From the 1959 articles identified, we reviewed 52 articles, of which 18 met the eligibility criteria. Twelve were descriptive/analytical studies, whereas six were simulation studies. There is no clear evidence for syndromic surveillance in terms of the ability to detect waterborne outbreaks (low sensitivity and high specificity). However, one simulation study implied that multiple sources of signals combined with spatial information may increase the timeliness in detecting a waterborne outbreak and reduce false alarms.

Conclusion

This review demonstrates that there is no conclusive evidence on the effectiveness of syndromic surveillance for the detection of waterborne outbreaks, thus suggesting the need to focus on primary prevention measures to reduce the risk of waterborne outbreaks. Future studies should investigate methods for combining health and environmental data with an assessment of needed financial and human resources for implementing such surveillance systems. In addition, a more critical thematic narrative synthesis on the most promising sources of data, and an assessment of the basis for arguments that joint analysis of different data or dimensions of data (e.g. spatial and temporal) might perform better, should be carried out.

Trial registration

PROSPERO: International prospective register of systematic reviews. 2019. CRD42019122332.
Antibodies against citrullinated proteins in relation to periodontitis with or without rheumatoid arthritis: a cross-sectional study
Authors: Lew Pit Hui , Rahman Mohammad Tariqur , Safii Syarida Hasnur , Baharuddin Nor Adinar , Bartold Peter Mark , Sockalingam Sargunan , Kassim Noor Lide Abu , Vaithilingam Rathna Devi
Published: July 2021

Background

Previous studies have reported conflicting findings between serum anti-citrullinated protein antibodies (ACPA) levels in rheumatoid arthritis (RA) participants with and without periodontitis (Pd). This study aimed to analyse possible correlations between serum ACPA levels and clinical parameters in Pd and RA participants.

Methods

Full mouth periodontal examination (probing pocket depth, clinical attachment levels, gingival bleeding index, visual plaque index) was conducted and serum samples obtained from 80 participants comprising RA, Pd, both RA and Pd (RAPd) and healthy individuals (HC). Erythrocyte sedimentation rates (ESR) and periodontal inflamed surface area (PISA) were obtained. Serum samples were analysed for ACPA quantification using enzyme-linked immunosorbent assay (ELISA).

Results

Median levels (IU/mL) of ACPA (interquartile range, IQR) in RAPd, RA, Pd and HC groups were 118.58(274.51), 102.02(252.89), 78.48(132.6) and 51.67(91.31) respectively. ACPA levels were significantly higher in RAPd and RA as compared to HC group (p < 0.05). However, ACPA levels of any of the groups were not correlated with any clinical periodontal and RA parameters within the respective groups.

Conclusions

At individual level, the amount of serum ACPA seem to have an increasing trend with the diseased condition in the order of RAPd > RA > Pd > HC. However, lack of any significant correlation between the serum ACPA levels with the clinical Pd and RA parameters warrants further studies to investigate the causal link between RA and Pd for such a trend. Further studies involving more inflammatory biomarkers might be useful to establish the causal link between Pd in the development and progression of RA or vice versa.
Oral health condition and development of frailty over a 12-month period in community‐dwelling older adults
Authors: Velázquez-Olmedo Laura Bárbara , Borges-Yáñez Socorro Aída , Andrade Palos Patricia , García-Peña Carmen , Gutiérrez-Robledo Luis Miguel , Sánchez-García Sergio
Published: July 2021

Background

To determine the association between oral health condition and development of frailty over a 12-month period in community-dwelling older adults.

Methods

Population-based, case-cohort study derived from the Cohort of Obesity, Sarcopenia, and Frailty of Older Mexican Adults (COSFOMA) study, including data from years 2015 and 2016. Using latent class analysis, we determined the oral health condition of older adults with teeth (t0), i.e., functional teeth, presence of coronal caries, root caries, periodontal disease, dental calculus, dental biofilm, root remains, xerostomia, and need for dental prosthesis. Edentulous was considered as a separate class. Criteria of the Frailty Phenotype (t1) by Fried et al. were used: weight loss, self-report of exhaustion, walking speed, decreased muscle strength, and low physical activity. The presence of three or more criteria indicated a frail condition. The strength of the association (odds ratio, OR) between oral health condition and development of frailty was estimated through bivariate analysis. Multiple logistic regression was used to adjust for the other variables of study: sociodemographic data (sex, age, marital status, level of education, paid work activity, and living alone), comorbidities, cognitive impairment, depressive symptoms, nutritional status, and use of oral health services.

Results

663 non-frail older adults were evaluated, with a mean age of 68.1 years (SD ± 6.1), of whom 55.7% were women. In t0, a three-class model with an acceptable value was obtained (entropy = 0.796). The study participants were classified as: edentulous persons (6.9%); Class 1 = Acceptable oral health (57.9%); Class 2 = Somewhat acceptable oral health (13.9%); and Class 3 = Poor oral health (21.3%). In t1, 18.0% (n = 97) of participants developed frailty. Using Acceptable oral health (Class 1) as a reference, we observed that older adults with edentulism (OR 4.1, OR adjusted 2.3) and Poor oral health (OR 2.4, OR adjusted 2.2) were at an increased risk of developing frailty compared to those with Acceptable oral health.

Conclusion

Older adults with edentulism and poor oral health had an increased risk of developing frailty over a 12-month period.
Women’s awareness regarding the use of dental imaging during pregnancy
Authors: Bahanan Lina , Tehsin Abdulrahman , Mousa Reyouf , Albadi Mohammed , Barayan Mohammed , Khan Emad , Khalifah Hanadi
Published: July 2021

Background

There is often anxiety among pregnant women about dental imaging during pregnancy. This may hinder some women from seeking dental treatment during pregnancy and consequently, may negatively affect the oral health of the mother and fetus. This study was conducted to assess women’s awareness regarding the use of dental imaging during pregnancy.

Methods

In this cross-sectional study, the electronic distribution of structured questionnaires was done via social media. The self-administered questionnaires contained questions related to women’s knowledge regarding the radiation protection measures during dental imaging, the safest period for dental imaging, the type of radiographs that can be acquired during pregnancy, and the possibility of radiation-induced malignancy and fetal malformation as a result of dental imaging.

Results

In total, 410 completed questionnaires were received and analyzed. More than half of the participants were 30–49 years of age. The majority of the participants (91%) demonstrated poor knowledge concerning dental imaging. Only 4% reported that pregnant women can have dental imaging during any trimester. The majority believed that panoramic images and cone-beam computed tomography should not be acquired during pregnancy. The majority also believed there is a high risk of congenital malformation due to dental imaging and were unsure about the oncogenic risks.

Conclusions

Our study suggests that there is insufficient knowledge about dental imaging safety during pregnancy. This misconception may have a direct impact on the attitude toward seeking dental care. Therefore, community awareness initiatives aimed at informing our society about radiation exposure, safety, and required protection measures are critical.
Investigating causal relationships between exposome and human longevity: a Mendelian randomization analysis
Authors: Huang Shu-Yi , Yang Yu-Xiang , Chen Shi-Dong , Li Hong-Qi , Zhang Xue-Qing , Kuo Kevin , Tan Lan , Feng Lei , Dong Qiang , Zhang Can , Yu Jin-Tai
Published: July 2021

Background

Environmental factors are associated with human longevity, but their specificity and causality remain mostly unclear. By integrating the innovative “exposome” concept developed in the field of environmental epidemiology, this study aims to determine the components of exposome causally linked to longevity using Mendelian randomization (MR) approach.

Methods

A total of 4587 environmental exposures extracting from 361,194 individuals from the UK biobank, in exogenous and endogenous domains of exposome were assessed. We examined the relationship between each environmental factor and two longevity outcomes (i.e., surviving to the 90th or 99th percentile age) from various cohorts of European ancestry. Significant results after false discovery rates correction underwent validation using an independent exposure dataset.

Results

Out of all the environmental exposures, eight age-related diseases and pathological conditions were causally associated with lower odds of longevity, including coronary atherosclerosis (odds ratio = 0.77, 95% confidence interval [0.70, 0.84], P = 4.2 × 10−8), ischemic heart disease (0.66, [0.51, 0.87], P = 0.0029), angina (0.73, [0.65, 0.83], P = 5.4 × 10−7), Alzheimer’s disease (0.80, [0.72, 0.89], P = 3.0 × 10−5), hypertension (0.70, [0.64, 0.77], P = 4.5 × 10−14), type 2 diabetes (0.88 [0.80, 0.96], P = 0.004), high cholesterol (0.81, [0.72, 0.91], P = 0.0003), and venous thromboembolism (0.92, [0.87, 0.97], P = 0.0028). After adjusting for genetic correlation between different types of blood lipids, higher levels of low-density lipoprotein cholesterol (0.72 [0.64, 0.80], P = 2.3 × 10−9) was associated with lower odds of longevity, while high-density lipoprotein cholesterol (1.36 [1.13, 1.62], P = 0.001) showed the opposite. Genetically predicted sitting/standing height was unrelated to longevity, while higher comparative height size at 10 was negatively associated with longevity. Greater body fat, especially the trunk fat mass, and never eat sugar or foods/drinks containing sugar were adversely associated with longevity, while education attainment showed the opposite.

Conclusions

The present study supports that some age-related diseases as well as education are causally related to longevity and highlights several new targets for achieving longevity, including management of venous thromboembolism, appropriate intake of sugar, and control of body fat. Our results warrant further studies to elucidate the underlying mechanisms of these reported causal associations.
Epicardial adipose tissue and severe Coronavirus Disease 19
Authors: Bihan Hélène , Heidar Richard , Beloeuvre Aude , Allard Lucie , Ouedraogo Elise , Tatulashvili Sopio , Tandjaoui Yacine , Gaudry Stephane , Brillet Pierre-Yves , Cosson Emmanuel
Published: July 2021

Background

Both visceral adipose tissue and epicardial adipose tissue (EAT) have pro-inflammatory properties. The former is associated with Coronavirus Disease 19 (COVID-19) severity. We aimed to investigate whether an association also exists for EAT.

Material and methods

We retrospectively measured EAT volume using computed tomography (CT) scans (semi-automatic software) of inpatients with COVID-19 and analyzed the correlation between EAT volume and anthropometric characteristics and comorbidities. We then analyzed the clinicobiological and radiological parameters associated with severe COVID-19 (O2 $$\ge$$
≥
6 l/min), intensive care unit (ICU) admission or death, and 25% or more CT lung involvement, which are three key indicators of COVID-19 severity.

Results

We included 100 consecutive patients; 63% were men, mean age was 61.8 ± 16.2 years, 47% were obese, 54% had hypertension, 42% diabetes, and 17.2% a cardiovascular event history. Severe COVID-19 (n = 35, 35%) was associated with EAT volume (132 ± 62 vs 104 ± 40 cm3, p = 0.02), age, ferritinemia, and 25% or more CT lung involvement. ICU admission or death (n = 14, 14%) was associated with EAT volume (153 ± 67 vs 108 ± 45 cm3, p = 0.015), hypertension and 25% or more CT lung involvement. The association between EAT volume and severe COVID-19 remained after adjustment for sex, BMI, ferritinemia and lung involvement, but not after adjustment for age. Instead, the association between EAT volume and ICU admission or death remained after adjustment for all five of these parameters.

Conclusions

Our results suggest that measuring EAT volume on chest CT scans at hospital admission in patients diagnosed with COVID-19 might help to assess the risk of disease aggravation.
Tumor microenvironment: a prospective target of natural alkaloids for cancer treatment
Authors: Luo Yanming , Yin Shuangshuang , Lu Jia , Zhou Shiyue , Shao Yingying , Bao Xiaomei , Wang Tao , Qiu Yuling , Yu Haiyang
Published: July 2021

Malignant tumor has become one of the major diseases that seriously endangers human health. Numerous studies have demonstrated that tumor microenvironment (TME) is closely associated with patient prognosis. Tumor growth and progression are strongly dependent on its surrounding tumor microenvironment, because the optimal conditions originated from stromal elements are required for cancer cell proliferation, invasion, metastasis and drug resistance. The tumor microenvironment is an environment rich in immune/inflammatory cells and accompanied by a continuous, gradient of hypoxia and pH. Overcoming immunosuppressive environment and boosting anti-tumor immunity may be the key to the prevention and treatment of cancer. Most traditional Chinese medicine have been proved to have good anti-tumor activity, and they have the advantages of better therapeutic effect and few side effects in the treatment of malignant tumors. An increasing number of studies are giving evidence that alkaloids extracted from traditional Chinese medicine possess a significant anticancer efficiency via regulating a variety of tumor-related genes, pathways and other mechanisms. This paper reviews the anti-tumor effect of alkaloids targeting tumor microenvironment, and further reveals its anti-tumor mechanism through the effects of alkaloids on different components in tumor microenvironment.
Health-related quality of life in amyotrophic lateral sclerosis using EQ-5D-5L
Authors: Wei Qian-Qian , Hou Yanbing , Chen Yongping , Ou Ruwei , Cao Bei , Zhang Lingyu , Yang Tianmi , Shang Huifang
Published: July 2021

Background

The study aimed to appraise the health-related quality of life (HRQoL) measured by the five-level EuroQol-5 dimensions (EQ-5D-5L) in amyotrophic lateral sclerosis (ALS), and to explore the associations between non-motor symptoms (mood changes, cognitive disturbances and sleep disturbances).

Methods

EQ-5D-5L descriptive scores were converted into a single aggregated “health utility” score. A calibrated visual analog scale (EQ-VAS) was used for self-rating of current health status. Multiple logistic regression analysis was used to explore the factors associated with HRQoL.

Results

Among the 547 enrolled ALS patients who were assessed using EQ-5D-5L, the highest frequency of reported problems was with usual activities (76.7%), followed by self-care (68.8%) and anxiety/depression (62.0%). The median health utility score was 0.78 and the median EQ-VAS score was 70. Clinical factors corresponding to differences in the EQ-5D-5L health utility score included age of onset, onset region, the ALS Functional Rating Scale-Revised (ALSFRS-R) score, and King’s College stages. Patients with depression, anxiety, and poor sleep had lower health utility scores. Patients with excessive daytime sleepiness and rapid eye movement sleep behavior disorder had lower EQ-VAS scores. Multivariate logistic analysis indicated that ALSFRS-R scores, depression, and anxiety were associated with health utility scores. After adjusting other parameters, ALSFRS-R score, stages, and depression were significantly associated with EQ-VAS scores (P < 0.05).

Conclusion

This study examined HRQoL in ALS patients using the Chinese version of the EQ-5D-5L scale across different stages of the disease. We found that HRQoL is related to disease severity and to mood disturbances. Management of non-motor symptoms may help improve HRQoL in ALS patients.
Role of α- and β-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease
Authors: Archer M. , Dogra N. , Dovey Z. , Ganta T. , Jang H.-S. , Khusid J. A. , Lantz A. , Mihalopoulos M. , Stockert J. A. , Zahalka A. , Björnebo L. , Gaglani S. , Noh M. R. , Kaplan S. A. , Mehrazin R. , Badani K. K. , Wiklund P. , Tsao K. , Lundon D. J. , Mohamed N. , Lucien F. , Padanilam B. , Gupta M. , Tewari A. K. , Kyprianou N.
Published: July 2021

The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis. Adrenergic receptors (adrenoceptors) are G-Protein coupled-receptors that are distributed throughout the body. The major function of α1-adrenoceptors is signaling smooth muscle contractions through GPCR and intracellular calcium influx. Pharmacologic intervention of α-and β-adrenoceptors is routinely and successfully implemented in the treatment of benign urologic illnesses, through the use of α-adrenoceptor antagonists. Furthermore, cell-based evidence recently established the antitumor effect of α1-adrenoceptor antagonists in prostate, bladder and renal tumors by reducing neovascularity and impairing growth within the tumor microenvironment via regulation of the phenotypic epithelial-mesenchymal transition (EMT). There has been a significant focus on repurposing the routinely used, Food and Drug Administration-approved α1-adrenoceptor antagonists to inhibit GU tumor growth and angiogenesis in patients with advanced prostate, bladder, and renal cancer. In this review we discuss the current evidence on (a) the signaling events of the autonomic nervous system mediated by its cognate α- and β-adrenoceptors in regulating the phenotypic landscape (EMT) of genitourinary organs; and (b) the therapeutic significance of targeting this signaling pathway in benign and malignant urologic disease.
NLRP3 inhibition attenuates early brain injury and delayed cerebral vasospasm after subarachnoid hemorrhage
Authors: Dodd William S. , Noda Imaray , Martinez Melanie , Hosaka Koji , Hoh Brian L.
Published: July 2021

Background

The NLRP3 inflammasome is a critical mediator of several vascular diseases through positive regulation of proinflammatory pathways. In this study, we defined the role of NLRP3 in both the acute and delayed phases following subarachnoid hemorrhage (SAH). SAH is associated with devastating early brain injury (EBI) in the acute phase, and those that survive remain at risk for developing delayed cerebral ischemia (DCI) due to cerebral vasospasm. Current therapies are not effective in preventing the morbidity and mortality associated with EBI and DCI. NLRP3 activation is known to drive IL-1β production and stimulate microglia reactivity, both hallmarks of SAH pathology; thus, we hypothesized that inhibition of NLRP3 could alleviate SAH-induced vascular dysfunction and functional deficits.

Methods

We studied NLRP3 in an anterior circulation autologous blood injection model of SAH in mice. Mice were randomized to either sham surgery + vehicle, SAH + vehicle, or SAH + MCC950 (a selective NLRP3 inhibitor). The acute phase was studied at 1 day post-SAH and delayed phase at 5 days post-SAH.

Results

NLRP3 inhibition improved outcomes at both 1 and 5 days post-SAH. In the acute (1 day post-SAH) phase, NLRP3 inhibition attenuated cerebral edema, tight junction disruption, microthrombosis, and microglial reactive morphology shift. Further, we observed a decrease in apoptosis of neurons in mice treated with MCC950. NLRP3 inhibition also prevented middle cerebral artery vasospasm in the delayed (5 days post-SAH) phase and blunted SAH-induced sensorimotor deficits.

Conclusions

We demonstrate a novel association between NLRP3-mediated neuroinflammation and cerebrovascular dysfunction in both the early and delayed phases after SAH. MCC950 and other NLRP3 inhibitors could be promising tools in the development of therapeutics for EBI and DCI.
Contributions of economic growth, terrestrial sinks, and atmospheric transport to the increasing atmospheric CO2 concentrations over the Korean Peninsula
Authors: Yun Jeongmin , Jeong Sujong
Published: July 2021

Background

Understanding a carbon budget from a national perspective is essential for establishing effective plans to reduce atmospheric CO2 growth. The national characteristics of carbon budgets are reflected in atmospheric CO2 variations; however, separating regional influences on atmospheric signals is challenging owing to atmospheric CO2 transport. Therefore, in this study, we examined the characteristics of atmospheric CO2 variations over South and North Korea during 2000–2016 and unveiled the causes of their regional differences in the increasing rate of atmospheric CO2 concentrations by utilizing atmospheric transport modeling.

Results

The atmospheric CO2 concentration in South Korea is rising by 2.32 ppm year− 1, which is more than the globally-averaged increase rate of 2.05 ppm year− 1. Atmospheric transport modeling indicates that the increase in domestic fossil energy supply to support manufacturing export-led economic growth leads to an increase of 0.12 ppm year− 1 in atmospheric CO2 in South Korea. Although enhancements of terrestrial carbon uptake estimated from both inverse modeling and process-based models have decreased atmospheric CO2 by up to 0.02 ppm year− 1, this decrease is insufficient to offset anthropogenic CO2 increases. Meanwhile, atmospheric CO2 in North Korea is also increasing by 2.23 ppm year− 1, despite a decrease in national CO2 emissions close to carbon neutrality. The great increases estimated in both South Korea and North Korea are associated with changes in atmospheric transport, including increasing emitted and transported CO2 from China, which have increased the national atmospheric CO2 concentrations by 2.23 ppm year− 1 and 2.27 ppm year− 1, respectively.

Conclusions

This study discovered that economic activity is the determinant of regional differences in increasing atmospheric CO2 in the Korea Peninsula. However, from a global perspective, changes in transported CO2 are a major driver of rising atmospheric CO2 over this region, yielding an increase rate higher than the global mean value. Our findings suggest that accurately separating the contributions of atmospheric transport and regional sources to the increasing atmospheric CO2 concentrations is important for developing effective strategies to achieve carbon neutrality at the national level.
Safety of exercise training in multiple sclerosis: a protocol for an updated systematic review and meta-analysis
Authors: Learmonth Y. C. , Pilutti L. A. , Herring M. P. , Motl R. W. , Chan B. , Metse A. P.
Published: July 2021

Background

There has been an exponential growth in the number of clinical research studies regarding exercise training in multiple sclerosis, and literature reviews and meta-analyses have documented the many benefits of exercise training. This research further requires careful review for documenting the safety of exercise training in multiple sclerosis, as clarity on safety represents a major hurdle in the clinical prescription of exercise behaviour.

Objectives

To enhance understanding of the feasibility of exercise in multiple sclerosis, we (1) provide a protocol of a systematic review and meta-analysis that summarises rates and risks of clinical relapse, adverse events (i.e., an unfavourable outcome that occurs during the intervention delivery time period), and serious adverse events (i.e., an untoward occurrence that results in death or is life threatening, requires hospitalisation, or results in disability during the intervention delivery time period), as well as retention, adherence, and compliance, from randomised controlled trials of exercise training in persons with multiple sclerosis; and (2) identify moderators of relapse, adverse events, and serious adverse event rates.

Methods

Eight field-relevant databases will be searched electronically. Studies that involve a randomised controlled trial of exercise training (with non-exercise, non-pharmacological, comparator), report on safety outcomes, and include adults with multiple sclerosis will be included. Rates and relative risks of the three primary outcomes (relapse, adverse event, and serious adverse event) will be calculated and reported each with standard error and 95% confidence interval. Random-effects meta-analysis will estimate mean population relative risk for outcomes. Potential sources of variability, including participant characteristics, features of the exercise stimulus, and comparison condition, will be examined with random-effects meta-regression with maximum likelihood estimation.

Discussion

The results from this systematic review and meta-analysis will inform and guide healthcare practitioners, researchers, and policymakers on the safety of exercise training in persons with multiple sclerosis. Where possible, we will identify the impact of exercise type, exercise delivery style, participant disability level, and the prescription of exercise guidelines, on the safety of exercise training. The result will identify critical information on the safety of exercise in persons with multiple sclerosis, while also identifying gaps in research and setting priorities for future enquiries.

Systematic review registration

PROSPERO 2020 CRD42020190544
The causal influence of responsive parenting behaviour on academic readiness: a protocol for a systematic review and meta-analysis of randomized controlled trials
Authors: Prime Heather , Andrews Krysta , Gonzalez Andrea , Janus Magdalena , Tricco Andrea C. , Bennett Teresa , Atkinson Leslie
Published: July 2021

Background

Children’s academic readiness has important implications for subsequent achievement and psychosocial functioning. A growing number of studies are utilizing randomized controlled trials (RCT) to examine whether responsive parenting interventions lead to positive gains in children’s academic readiness. A synthesis of the extant literature is warranted to gain a precise estimate of the causal influence of responsive parenting on academic readiness, as well as to examine moderators that may serve to strengthen or weaken this effect. The main objective of this study will be to conduct a systematic review and meta-analysis of RCTs evaluating the use of responsive parenting interventions to target academic readiness: problem-solving/reasoning, language proficiency, executive functioning, and pre-academic skills (e.g., numeracy/literacy).

Methods

Studies that took place in the early childhood period (< 6 years at baseline), targeted responsive parenting behaviours using an RCT (with control group, waitlist, or treatment as usual as a comparator), and included an outcome assessment of academic readiness will be considered for eligibility. Children and/or parents with special needs and/or disabilities will be excluded. The primary outcome is the effect of responsive parenting interventions on academic readiness. Secondary outcomes include substantive and methodological moderators and parent-mediated effects on outcomes. We will search MEDLINE, PsycINFO, ERIC, and ProQuest Dissertations & Theses Global databases from their inception onwards and we will also conduct backward/forward searching of eligible studies. Published and unpublished works will be considered. Screening, full-text assessments, and data extraction will be completed by two independent reviewers. Risk of bias will be assessed using the CLARITY tool for RCTs. Effect sizes will be calculated based on study-level standardized differences between experimental and control groups and entered into random effects models to obtain a pooled effect (meta-analysis). Moderation will be examined through Q-statistics and meta-regression to study sources of between-study variation in effect sizes. A pooled path model of mediation will be used to study parent-mediated effects.

Discussion

Findings will illuminate causal relations between responsive parenting and academic readiness, with implications for developmental science. Findings will also guide decision making in policy and practice for supporting early childhood development and reducing social disparities in children prior to school-entry.

Systematic review registration

PROSPERO CRD42020222143.