bluuebunny/crossref_metadata_2025 huggingface dataset:
Bronchial artery embolization for the management of frequent hemoptysis caused by bronchiectasis
Authors: Lu Guang-Dong , Yan Hai-Tao , Zhang Jin-Xing , Liu Sheng , Shi Hai-Bin , Zu Qing-Quan
Published: November 2022

Background

To retrospectively evaluate the effectiveness of bronchial artery embolization (BAE) compared with conservative therapy for the treatment of frequent hemoptysis caused by bronchiectasis.

Methods

From January 2015 to December 2019, consecutive patients who were admitted due to frequent (more than three times per year) bronchiectasis-related hemoptysis were retrospectively reviewed. Those who were treated with either BAE (n = 69) or conservative therapy (n = 47) were enrolled for analysis. The technical success, clinical success, and complications of the BAE procedure were evaluated. Long-term hemoptysis-free survival rates and clinical success were compared between patients in the BAE group and patients in the conservative group. A Cox proportional hazard regression model was used to identify the predictors of recurrent hemoptysis.

Results

The technical success rate was 100% for the BAE procedure, and clinical success was achieved in 92.8% (64 of 69) of cases. No major procedure-related complications occurred, and minor complications were observed in 16 cases (23.2%). The 1-, 2-, and 3-year hemoptysis-free survival rates were 88.3, 71.3, and 66.2%, respectively, for the BAE group and 31.9, 17.6, and 2.5%, respectively, for the conservative treatment group (P <  0.001). Multivariate analysis showed that BAE was a protective factor against recurrent hemoptysis in treated patients. In addition, the presence of cystic bronchiectasis was the only independent risk factor for rebleeding in the whole population and in the BAE group.

Conclusions

BAE may provide an effective option for patients with frequent bronchiectasis-related hemoptysis, especially for those without cystic bronchiectasis.
What do Turkish, Spanish, and Pakistani medical students value in specialty training positions? A discrete choice experiment
Authors: Kıyak Yavuz Selim , Budakoğlu Işıl İrem , García-Estañ Joaquín , Atta Komal , Coşkun Özlem , Koyun Emin
Published: November 2022

Background:

The aim of this study was to find out specialty training preferences of senior medical students from three medical schools in Turkey, Spain, and Pakistan.

Methods:

A Discrete Choice Experiment was carried out using an electronic form for students in three countries in 2021–2022 term. Each choice set in the form consisted of two hypothetical specialty training positions. The attributes were location, earnings, working conditions, personal perspective, quality of education, probability of malpractice, and prestige. Conditional logit model was used to estimate participants’ preferences and “willingness to accept” values.

Results:

The most valued attribute was “personal perspective on specialty area” for Turkish and Spanish students, while this attribute was not meaningful for Pakistani students. Turkish students needed a 204% of change in their income for a swap between the specialty that they like and not like. This tradeoff necessitated a 300% change for Spanish students. The most valued attribute for Pakistani students, which was “working conditions”, necessitated a 97% increase in income to switch from working in good conditions to working in poor conditions.

Conclusion:

In this first multinational DCE study in the medical education literature, we found the preferences of medical students in Turkey, Spain, and Pakistan are affected to various extents by several factors.
The view of Hong Kong parents on secondary use of dried blood spots in newborn screening program
Authors: Hui L. L. , Nelson E. A.S. , Deng H. B. , Leung T. Y. , Ho C. H. , Chong J. S.C. , Fung G. P.G. , Hui J. , Lam H. S.
Published: November 2022

Background

Residual dried blood spots (rDBS) from newborn screening programmes represent a valuable resource for medical research, from basic sciences, through clinical to public health. In Hong Kong, there is no legislation for biobanking. Parents’ view on the retention and use of residual newborn blood samples could be cultural-specific and is important to consider for biobanking of rDBS.

Objective

To study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents.

Methods

A mixed-method approach was used to study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents of children 0–3 years or expecting parents through focus groups (8 groups; 33 participants) and a survey (n = 1012, 85% mothers) designed with insights obtained from the focus groups. We used framework analysis to summarise the themes as supportive factors, concerns and critical arguments for retention and secondary use of rDBS from focus group discussion. We used multiple logistic regression to assess factors associated with support for retention and secondary use of rDBS in the survey.

Results

Both in focus groups and survey, majority of parents were not aware of the potential secondary use of rDBS. Overall secondary use of rDBS in medical research was well accepted by a large proportion of Hong Kong parents, even if all potential future research could not be specified in a broad consent. However parents were concerned about potential risks of biobanking rDBS including leaking of data and mis-use of genetic information. Parents wanted to be asked for permission before rDBS are stored and mainly did not accept an “opt-out” approach. The survey showed that parents born in mainland China, compared to Hong Kong born parents, had lower awareness of newborn screening but higher support in biobanking rDBS. Higher education was associated with support in rDBS biobanking only among fathers.

Conclusion

Long-term storage and secondary use of rDBS from newborn screening for biomedical research and a broad consent for biobanking of rDBS are generally acceptable to Hong Kong parents given their autonomy is respected and their privacy is protected, highlighting the importance of an accountable governance and a transparent access policy for rDBS biobanks.
Prophylactic antibiotic use during labor and delivery in China: a nationwide, multicenter, hospital-based, cross-sectional study
Authors: Lian Qiguo , Zheng Tao , Huo Xiaona , Zhang Jun , Zhang Lin
Published: November 2022

Background

Prophylactic antibiotic use during delivery is common in routine obstetric practice to prevent infection globally, especially in low- and middle-income countries. In China, however, little is currently known about the national estimates for prophylactic antibiotic use during delivery. Therefore, we aimed to describe the prevalence of prophylactic antibiotic use and guideline adherence using national data in China.

Methods

This cross-sectional study analyzed a national dataset from the China Labor and Delivery Survey in 2015–2016. The primary outcomes were prophylactic antibiotic use and clinician adherence to WHO recommendations for the prevention and treatment of maternal peripartum infections. We estimated the weighted prevalence of the outcomes with Taylor series linearization and investigated the associated factors of the outcomes with logistic regression.

Results

Of the 72,519 deliveries, the prevalence of antibiotic prophylaxis was 52.0%, varying from 92.8% in Shanxi to 17.3% in Hainan. The prevalence of clinician adherence to the WHO guideline was 79.9%, ranging from 93.4% in Shandong to 50.0% in Shanxi. Prophylactic antibiotic use was associated with cesarean delivery (AOR, 55.77; 95%CI, 25.74–120.86), operative vaginal delivery (AOR, 4.00; 95%CI, 1.64–9.78), preterm (AOR, 1.96; 95%CI, 1.60–2.41), premature rupture of membranes (PROM) (AOR, 2.80; 95%CI, 1.87–4.18), and meconium-stained amniotic fluid (AOR, 1.91; 95%CI, 1.30–2.81) in all deliveries and also episiotomy (AOR, 1.48; 95%CI, 1.02–2.16) in vaginal deliveries. Clinician adherence was positively associated with cesarean delivery (AOR, 5.72; 95%CI, 2.74–11.93) while negatively associated with operative vaginal delivery (AOR, 0.26; 95%CI, 0.11–0.61), PROM (AOR, 0.50; 95%CI, 0.35–0.70), and meconium-stained amniotic fluid (AOR, 0.66; 95%CI, 0.48–0.91) in all deliveries. In vaginal deliveries, clinician adherence was negatively associated with episiotomy (AOR, 0.67; 95%CI, 0.46–0.96) and severe perineal trauma (AOR, 0.09; 95%CI, 0.02–0.44). Besides, clinicians in general hospitals prescribed prophylactic antibiotics more likely (AOR, 2.79; 95%CI, 1.50–5.19) and had a lower adherence (AOR, 0.38; 95%CI, 0.20–0.71) than their peers in maternity hospitals.

Conclusions

We observed that about half of all deliveries in China received antibiotics for prophylaxis, and most deliveries were prescribed according to the WHO guideline. Furthermore, the two prevalence rates for prophylactic antibiotic use and clinician adherence varied widely across provinces of China.
Mendelian randomization analysis of factors related to ovulation and reproductive function and endometrial cancer risk
Authors: D’Urso Shannon , Arumugam Pooja , Weider Therese , Hwang Liang-Dar , Bond Tom A. , Kemp John P. , Warrington Nicole M. , Evans David M. , O’Mara Tracy A. , Moen Gunn-Helen
Published: November 2022

Background

Observational epidemiological studies suggest a link between several factors related to ovulation and reproductive function and endometrial cancer (EC) risk; however, it is not clear whether these relationships are causal, and whether the risk factors act independently of each other. The aim of this study was to investigate putative causal relationships between the number of live births, age at last live birth, and years ovulating and EC risk. 

Methods

We conducted a series of observational analyses to investigate various risk factors and EC risk in the UK Biobank (UKBB). Additionally, multivariate analysis was performed to elucidate the relationship between the number of live births, age at last live birth, and years ovulating and other related factors such as age at natural menopause, age at menarche, and body mass index (BMI). Secondly, we used Mendelian randomization (MR) to assess if these observed relationships were causal. Genome-wide significant single nucleotide polymorphisms (SNPs) were extracted from previous studies of woman’s number of live births, age at menopause and menarche, and BMI. We conducted a genome-wide association analysis using the UKBB to identify SNPs associated with years ovulating, years using the contraceptive pill, and age at last live birth.

Results

We found evidence for a causal effect of the number of live births (inverse variance weighted (IVW) odds ratio (OR): 0.537, p = 0.006), the number of years ovulating (IVW OR: 1.051, p = 0.014), in addition to the known risk factors BMI, age at menarche, and age at menopause on EC risk in the univariate MR analyses. Due to the close relationships between these factors, we followed up with multivariable MR (MVMR) analysis. Results from the MVMR analysis showed that number of live births had a causal effect on EC risk (OR: 0.783, p = 0.036) independent of BMI, age at menarche and age at menopause.

Conclusions

MVMR analysis showed that the number of live births causally reduced the risk of EC.
Maternal factors during pregnancy influencing maternal, fetal, and childhood outcomes
Authors: Muglia Louis J. , Benhalima Katrien , Tong Stephen , Ozanne Susan
Published: November 2022

Enhancing pregnancy health is known to improve the mother’s and offspring’s life-long well-being. The maternal environment, encompassing genetic factors, impacts of social determinants, the nutritional/metabolic milieu, and infections and inflammation, have immediate consequences for the in utero development of the fetus and long-term programming into childhood and adulthood. Moreover, adverse pregnancy outcomes such as preterm birth or preeclampsia, often attributed to the maternal environmental factors listed above, have been associated with poor maternal cardiometabolic health after pregnancy. In this BMC Medicine article collection, we explore a broad spectrum of maternal characteristics across pregnancy and postnatal phenotypes, anticipating substantial cross-fertilization of new understanding and shared mechanisms around diverse outcomes. Advances in the ability to leverage ‘omics across different platforms (genome, transcriptome, proteome, metabolome, microbiome, lipidome), large high-dimensional population databases, and unique cohorts are generating exciting new insights: The first articles in this collection highlight the role of placental biomarkers of preterm birth, metabolic influences on fetal and childhood growth, and the impact of common pre-existing maternal disorders, obesity and smoking on pregnancy outcomes, and the child’s health. As the collection grows, we look forward to seeing the connections emerge across maternal, fetal, and childhood outcomes that will foster new insights and preventative strategies for women.
Alterations of DNA methylation and expression of genes related to thyroid hormone metabolism in colon epithelium of obese patients
Authors: Shimi Ghazaleh , Pourvali Katayoun , Ghorbani Arman , Nooshin Sajad , Zare Karizi Shohreh , Iranirad Reza , Zand Hamid
Published: November 2022

Background

Colorectal cancer is common among obese individuals. The purpose of the current study was to determine changes in DNA methylation status and mRNA expression of thyroid hormone receptor beta (THRB), as a tumor suppressor, and thyroid hormone inactivating enzyme, type 3 deiodinase (DIO3) genes, in human epithelial colon tissues of healthy obese individuals.

Methods

Colon biopsies were analyzed by methylation sensitive-high resolution melting (MS-HRM) to investigate promoter methylation of DIO3 and THRB, and by quantitative real-time polymerase chain reaction to assay expression of DIO3 and THRB mRNA on eighteen obese and twenty-one normal-weight healthy men.

Results

There was no significant difference in mean methylation levels at the THRB promoter region between the two groups. Nevertheless, obesity decreased THRB expression levels, significantly (P < 0.05; fold change: 0.19). Furthermore, obesity attenuated DNA methylation (P < 0.001) and enhanced mRNA expression of DIO3 (P < 0.05; fold change: 3).

Conclusions

Our findings suggest that obesity may alter expression of THRB and DIO3 genes through epigenetic mechanism. Alterations of THRB and DIO3 expressions may predispose colon epithelium of obese patients to neoplastic transformation.
NK cells and solid tumors: therapeutic potential and persisting obstacles
Authors: Tong Le , Jiménez-Cortegana Carlos , Tay Apple H.M. , Wickström Stina , Galluzzi Lorenzo , Lundqvist Andreas
Published: November 2022

Natural killer (NK) cells, which are innate lymphocytes endowed with potent cytotoxic activity, have recently attracted attention as potential anticancer therapeutics. While NK cells mediate encouraging responses in patients with leukemia, the therapeutic effects of NK cell infusion in patients with solid tumors are limited. Preclinical and clinical data suggest that the efficacy of NK cell infusion against solid malignancies is hampered by several factors including inadequate tumor infiltration and persistence/activation in the tumor microenvironment (TME). A number of metabolic features of the TME including hypoxia as well as elevated levels of adenosine, reactive oxygen species, and prostaglandins negatively affect NK cell activity. Moreover, cancer-associated fibroblasts, tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells actively suppress NK cell-dependent anticancer immunity. Here, we review the metabolic and cellular barriers that inhibit NK cells in solid neoplasms as we discuss potential strategies to circumvent such obstacles towards superior therapeutic activity.
Prevalence and pathology of equine parvovirus-hepatitis in racehorses from New York racetracks
Authors: Jager Mason C. , Tomlinson Joy E. , Henry Caitlin E. , Fahey Megan J. , Van de Walle Gerlinde R.
Published: November 2022

Background

Theiler’s disease, a.k.a. equine serum hepatitis, is a devastating, highly fatal disease of horses. Equine parvovirus-hepatitis (EqPV-H) has been identified as the likely cause of this disease. While the incidence of Theiler’s disease is low, the prevalence of EqPV-H DNA in horses is high, with up to 37% in some regions, suggesting that subclinical or persistent infection is common.

Methods

To determine the prevalence and pathogenicity of EqPV-H infection at New York racetracks, DNA was extracted from archived formalin-fixed, paraffin-embedded liver tissues from racehorses submitted for necropsy to the Animal Health Diagnostic Center as part of the New York State Gaming Commission-Cornell University postmortem examination program. A total of 191 liver samples from horses between 2 and 13 years old were evaluated. Extracted DNA was tested for EqPV-H using PCR and gel electrophoresis. PCR-positive samples were further assessed for tissue morphology using histology and detection of viral nucleic acid using in situ hybridization.

Results

Forty-two samples were PCR positive (22%). Of those, 31 samples had positive viral nucleic acid hybridization in hepatocytes with 11 samples showing positive hybridization in necrotic hepatocytes associated with inflammatory cells, indicating active hepatitis. Both individual hepatocyte necrosis and hepatitis were positively associated with EqPV-H detection (p < 0.0001 and p = 0.0005, respectively).

Conclusion

These findings indicate that presence of EqPV-H in the liver and parvoviral-associated hepatitis are prevalent in racehorses from New York racetracks, thus warranting additional studies examining potential associations between EqPV-H infection and racehorse performance.
Human intracranial pulsatility during the cardiac cycle: a computational modelling framework
Authors: Causemann Marius , Vinje Vegard , Rognes Marie E.
Published: November 2022

Background

Today’s availability of medical imaging and computational resources set the scene for high-fidelity computational modelling of brain biomechanics. The brain and its environment feature a dynamic and complex interplay between the tissue, blood, cerebrospinal fluid (CSF) and interstitial fluid (ISF). Here, we design a computational platform for modelling and simulation of intracranial dynamics, and assess the models’ validity in terms of clinically relevant indicators of brain pulsatility. Focusing on the dynamic interaction between tissue motion and ISF/CSF flow, we treat the pulsatile cerebral blood flow as a prescribed input of the model.

Methods

We develop finite element models of cardiac-induced fully coupled pulsatile CSF flow and tissue motion in the human brain environment. The three-dimensional model geometry is derived from magnetic resonance images (MRI) and features a high level of detail including the brain tissue, the ventricular system, and the cranial subarachnoid space (SAS). We model the brain parenchyma at the organ-scale as an elastic medium permeated by an extracellular fluid network and describe flow of CSF in the SAS and ventricles as viscous fluid movement. Representing vascular expansion during the cardiac cycle, a prescribed pulsatile net blood flow distributed over the brain parenchyma acts as the driver of motion. Additionally, we investigate the effect of model variations on a set of clinically relevant quantities of interest.

Results

Our model predicts a complex interplay between the CSF-filled spaces and poroelastic parenchyma in terms of ICP, CSF flow, and parenchymal displacements. Variations in the ICP are dominated by their temporal amplitude, but with small spatial variations in both the CSF-filled spaces and the parenchyma. Induced by ICP differences, we find substantial ventricular and cranial-spinal CSF flow, some flow in the cranial SAS, and small pulsatile ISF velocities in the brain parenchyma. Moreover, the model predicts a funnel-shaped deformation of parenchymal tissue in dorsal direction at the beginning of the cardiac cycle.

Conclusions

Our model accurately depicts the complex interplay of ICP, CSF flow and brain tissue movement and is well-aligned with clinical observations. It offers a qualitative and quantitative platform for detailed investigation of coupled intracranial dynamics and interplay, both under physiological and pathophysiological conditions.
Comment on “The effect of disease-modifying anti-rheumatic drugs on skeletal muscle mass in rheumatoid arthritis patients: a systematic review with meta-analysis”
Authors: Minamino Hiroto , Torii Mie , Katsushima Masao , Fujita Yoshihito , Hashimoto Motomu
Published: November 2022

We read with great interest the article by Hein et al., which described the meta-analysis study on the impact of disease-modifying anti-rheumatic drugs (DMARDs) therapy on skeletal muscle mass in rheumatoid arthritis (RA) patients. While the data presented are impressive, we add some remarks about methodological issues that should be considered. First, this meta-analysis does not include several necessary studies that have provided data on the relationship between anti-tumor necrosis factor (anti-TNF) therapy and body composition. To make the meta-analysis more comprehensive, it could be necessary to incorporate these studies into this analysis. Second, this study did not employ a representative measure of skeletal muscle mass that was adjusted for body size, such as skeletal muscle mass index (SMI). It is well recognized that skeletal muscle mass varies with body size, particularly height and body mass index. Given the heterogeneity background of body size in the studies included in this meta-analysis, it may be worthwhile to conduct an additional analysis regarding the associations between DMARDs and the adjusted measure of skeletal muscle mass such as SMI, which is recommended in several guidelines when determining and contrasting the quantity of skeletal muscle mass. Third, when determining body composition, several reports show variances between bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DEXA) in RA as well as in general. In this regard, it may not be appropriate to simultaneously perform a meta-analysis of skeletal muscle mass determined by DEXA and BIA. With the issues described above, we conclude by recommending additional investigations to strengthen the arguments presented by this valuable meta-analysis.
Within-week differences in external training load demands in elite volleyball players
Authors: Akyildiz Zeki , de Oliveira Castro Henrique , Çene Erhan , Laporta Lorenzo , Parim Coskun , Altundag Emre , Akarçeşme Cengiz , Guidetti Giovanni , Miale Giovanni , Silva Ana Filipa , Nobari Hadi , Clemente Filipe Manuel
Published: November 2022

Purpose

The aim of this study was to analyze the within-week differences in external training intensity in different microcycles considering different playing positions in women elite volleyball players.

Methods

The training and match data were collected during the 2020–2021 season, which included 10 friendly matches, 41 league matches and 11 champions league matches. The players’ position, training/match duration, training/match load, local positioning system (LPS) total distance, LPS jumps, accelerations, decelerations, high metabolic load distance (HMLD), acute and chronic (AC) mean and AC ratio calculated with the rolling average (RA) method and the exponentially weighted moving average (EWMA) method, monotony and strain values were analyzed.

Results

All the variables except strain, Acc/Dec ratio and acute mean (RA) showed significant differences among distance to match days. Regarding the players’ positions, the only difference was found in the AC ratio (EWMA); in all microcycles, the middle blocker player showed workload values when compared with the left hitter, setter and libero.

Conclusion

Overall, the analysis revealed that the intensity of all performance indicators, except for strain, acc/dec and acute mean load (RA), showed significant differences among distance to match day with moderate to large effect sizes. When comparing players’ positions, the middle blocker accumulated the lowest loads. There were no significant differences among other positions.
A correlation map of genome-wide DNA methylation patterns between paired human brain and buccal samples
Authors: Sommerer Yasmine , Ohlei Olena , Dobricic Valerija , Oakley Derek H. , Wesse Tanja , Sedghpour Sabet Sanaz , Demuth Ilja , Franke Andre , Hyman Bradley T. , Lill Christina M. , Bertram Lars
Published: November 2022

Epigenome-wide association studies (EWAS) assessing the link between DNA methylation (DNAm) and phenotypes related to structural brain measures, cognitive function, and neurodegenerative diseases are becoming increasingly more popular. Due to the inaccessibility of brain tissue in humans, several studies use peripheral tissues such as blood, buccal swabs, and saliva as surrogates. To aid the functional interpretation of EWAS findings in such settings, there is a need to assess the correlation of DNAm variability across tissues in the same individuals. In this study, we performed a correlation analysis between DNAm data of a total of n = 120 matched post-mortem buccal and prefrontal cortex samples. We identified nearly 25,000 (3% of approximately 730,000) cytosine-phosphate-guanine (CpG) sites showing significant (false discovery rate q < 0.05) correlations between buccal and PFC samples. Correlated CpG sites showed a preponderance to being located in promoter regions and showed a significant enrichment of being determined by genetic factors, i.e. methylation quantitative trait loci (mQTL), based on buccal and dorsolateral prefrontal cortex mQTL databases. Our novel buccal–brain DNAm correlation map will provide a valuable resource for future EWAS using buccal samples for studying DNAm effects on phenotypes relating to the brain. All correlation results are made freely available to the public online.
High phytosterol levels in corn cobs point to their sustainable use as a nutritional source
Authors: Bae Hwan-Hee , Ha Jun Young , Go Young Sam , Son Jae-Han , Son Beom-Young , Kim Jae-Hong , Shin Seonghyu , Jung Tae-Wook , Yi Gibum
Published: November 2022

Phytosterols are important structural components of plant cells that affect membrane fluidity, permeability, and membrane-related metabolic regulation. These compounds, which are abundant in vegetable oils and corn kernel oil, are also beneficial for human health. Cultivation of corn (Zea mays L.) produces huge amounts of cobs as a by-product, but efforts to utilize cobs are still limited. Here, we investigated phytosterol, crude oil, and fatty acid contents in the kernels and cobs of four major corn cultivars in South Korea and explored the potential use of cobs as a source of phytosterols. Total phytosterol levels were two times higher in cobs (68.0–217.1 mg 100 g−1 DW) than in kernels (43.8–89.5 mg 100 g−1 DW) and were highest in the kernels and cobs of Sinhwangok at 60 days after pollination. We showed that not only kernels but also cobs can be a rich source of phytosterols. The results also revealed that the amount of phytosterol is depending on a genetic background as well as developmental stages suggesting further investigation would enhance the utilization of corn cobs as a phytosterol source.
The natural FGF-trap long pentraxin 3 inhibits lymphangiogenesis and lymphatic dissemination
Authors: Turati Marta , Giacomini Arianna , Rezzola Sara , Maccarinelli Federica , Gazzaroli Giorgia , Valentino Sonia , Bottazzi Barbara , Presta Marco , Ronca Roberto
Published: November 2022

The lymphatic vascular system represents a major route for dissemination of several solid tumors, including melanoma. Even though the members of the Vascular Endothelial Growth Factor family VEGF-C and VEGF-A have been shown to drive tumor lymphangiogenesis, experimental evidence indicates that also the pro-angiogenic factor Fibroblast Growth Factor-2 (FGF2) may play a role in the lymphangiogenic switch by triggering the activation of lymphatic endothelial cells (LECs) in cooperation with VEGFs.

The soluble pattern recognition receptor Long Pentraxin 3 (PTX3) acts as a natural FGF trap, thus exerting an oncosuppressive role in FGF-dependent tumors. Here, the capacity of PTX3 to modulate lymphangiogenesis was assessed in vitro and in vivo. The results demonstrate that recombinant human PTX3 inhibits the lymphangiogenic activity exerted by the VEGF-A/FGF2/sphingosine-1-phosphate (VFS) cocktail on human and murine LECs. In keeping with in vitro data, a reduced lymphangiogenic response was observed in a lymphangiogenic Matrigel plug assay following the subcutaneous injection of the VFS cocktail in PTX3-overexpressing transgenic TgN(Tie2-hPTX3) mice when compared to wild-type or Ptx3 null animals. Accordingly, the capacity of B16F10-VEGFC-luc melanoma cells to colonize the primary tumor-draining lymph node after grafting into the foot pad was dramatically impaired in PTX3-overexpressing mice.

Together with the observation that both the VFS cocktail and melanoma cell conditioned media caused a significant downregulation of PTX3 expression in LECs, these data indicate that the FGF trap activity of PTX3 may exert a key effect in the modulation of lymphangiogenesis and tumor metastatic dissemination.
De novo mutations within metabolism networks of amino acid/protein/energy in Chinese autistic children with intellectual disability
Authors: Chen Wen-Xiong , Liu Bin , Zhou Lijie , Xiong Xiaoli , Fu Jie , Huang Zhi-Fang , Tan Ting , Tang Mingxi , Wang Jun , Tang Ya-Ping
Published: November 2022

Background

Autism spectrum disorder (ASD) is often accompanied by intellectual disability (ID). Despite extensive studies, however, the genetic basis for this comorbidity is still not clear. In this study, we tried to develop an analyzing pipeline for de novo mutations and possible pathways related to ID phenotype in ASD. Whole-exome sequencing (WES) was performed to screen de novo mutations and candidate genes in 79 ASD children together with their parents (trios). The de novo altering genes and relative pathways which were associated with ID phenotype were analyzed. The connection nodes (genes) of above pathways were selected, and the diagnostic value of these selected genes for ID phenotype in the study population was also evaluated.

Results

We identified 89 de novo mutant genes, of which 34 genes were previously reported to be associated with ASD, including double hits in the EGF repeats of NOTCH1 gene (p.V999M and p.S1027L). Interestingly, of these 34 genes, 22 may directly affect intelligence quotient (IQ). Further analyses revealed that these IQ-related genes were enriched in protein synthesis, energy metabolism, and amino acid metabolism, and at least 9 genes (CACNA1A, ALG9, PALM2, MGAT4A, PCK2, PLEKHA1, PSME3, ADI1, and TLE3) were involved in all these three pathways. Seven patients who harbored these gene mutations showed a high prevalence of a low IQ score (< 70), a non-verbal language, and an early diagnostic age (< 4 years). Furthermore, our panel of these 9 genes reached a 10.2% diagnostic rate (5/49) in early diagnostic patients with a low IQ score and also reached a 10% diagnostic yield in those with both a low IQ score and non-verbal language (4/40).

Conclusion

We found some new genetic disposition for ASD accompanied with intellectual disability in this study. Our results may be helpful for etiologic research and early diagnoses of intellectual disability in ASD. Larger population studies and further mechanism studies are warranted.
Summarising data and factors associated with COVID-19 related conspiracy theories in the first year of the pandemic: a systematic review and narrative synthesis
Authors: Tsamakis Konstantinos , Tsiptsios Dimitrios , Stubbs Brendon , Ma Ruimin , Romano Eugenia , Mueller Christoph , Ahmad Ayesha , Triantafyllis Andreas S. , Tsitsas George , Dragioti Elena
Published: November 2022

Conspiracy theories can have particularly harmful effects by negatively shaping health-related behaviours. A significant number of COVID-19 specific conspiracy theories emerged in the immediate aftermath of the pandemic outbreak. The aim of this study was to systematically review the literature on conspiracy theories related to COVID-19 during the first year of the pandemic (2020), to identify their prevalence, their determinants and their public health consequences. A comprehensive literature search was carried out in PubMed and PsycINFO to detect all studies examining any conspiracy theory related to COVID-19 between January 1st 2020, and January 10th 2021. Forty-three studies were included with a total of 61,809 participants. Between 0.4 and 82.7% of participants agreed with at least one conspiracy belief. Certain sociodemographic factors (young age, female gender, being non-white, lower socioeconomic status), psychological aspects (pessimism, blaming others, anger) and other qualities (political conservatism, religiosity, mistrust in science and using social media as source of information) were associated with increased acceptance of conspiracy theories. Conspiracy beliefs led to harmful health-related behaviours and posed a serious public health threat. Large-scale collaborations between governments and healthcare organizations are needed to curb the spread of conspiracy theories and their adverse consequences.
Nanoarchitectonics-based model membrane platforms for probing membrane-disruptive interactions of odd-chain antimicrobial lipids
Authors: Yoon Bo Kyeong , Tan Sue Woon , Tan Jia Ying Brenda , Jackman Joshua A. , Cho Nam-Joon
Published: November 2022

The use of nanoscience tools to investigate how antimicrobial lipids disrupt phospholipid membranes has greatly advanced molecular-level biophysical understanding and opened the door to new application possibilities. Until now, relevant studies have focused on even-chain antimicrobial lipids while there remains an outstanding need to investigate the membrane-disruptive properties of odd-chain antimicrobial lipids that are known to be highly biologically active. Herein, using the quartz crystal microbalance-dissipation (QCM-D) and electrochemical impedance spectroscopy (EIS) techniques, we investigated how an 11-carbon, saturated fatty acid and its corresponding monoglyceride—termed undecanoic acid and monoundecanoin, respectively—disrupt membrane-mimicking phospholipid bilayers with different nanoarchitectures. QCM-D tracking revealed that undecanoic acid and monoundecanoin caused membrane tubulation and budding from supported lipid bilayers, respectively, and were only active above their experimentally determined critical micelle concentration (CMC) values. Monoundecanoin was more potent due to a lower CMC and electrochemical impedance spectroscopy (EIS) characterization demonstrated that monoundecanoin caused irreversible membrane disruption of a tethered lipid bilayer platform at sufficiently high compound concentrations, whereas undecanoic acid only induced transient membrane disruption. This integrated biophysical approach also led us to identify that the tested 11-carbon antimicrobial lipids cause more extensive membrane disruption than their respective 12-carbon analogues at 2 × CMC, which suggests that they could be promising molecular components within next-generation antimicrobial nanomedicine strategies.
Isolation and characterization of extracellular vesicles from biotechnologically important fungus Aureobasidium pullulans
Authors: Černoša Anja , Gostinčar Cene , Lavrin Teja , Kostanjšek Rok , Lenassi Metka , Gunde-Cimerman Nina
Published: November 2022

Extracellular vesicles (EVs) are increasingly recognized as an important mechanism for cell–cell interactions. Their role in fungi is still poorly understood and they have been isolated from only a handful of species. Here, we isolated and characterized EVs from Aureobasidium pullulans, a biotechnologically important black yeast-like fungus that is increasingly used for biocontrol of phytopathogenic fungi and bacteria. After optimization of the isolation protocol, characterization of EVs from A. pullulans by transmission electron microscopy (TEM) revealed a typical cup-shaped morphology and different subpopulations of EVs. These results were confirmed by nanoparticle tracking analysis (NTA), which revealed that A. pullulans produced 6.1 × 108 nanoparticles per milliliter of culture medium. Proteomic analysis of EVs detected 642 proteins. A small fraction of them had signal peptides for secretion and transmembrane domains. Proteins characteristic of different synthesis pathways were found, suggesting that EVs are synthesized by multiple pathways in A. pullulans. Enrichment analysis using Gene Ontology showed that most of the proteins found in the EVs were associated with primary metabolism. When sequencing the small RNA fraction of A. pullulans EVs, we found two hypothetical novel mil-RNAs. Finally, we tested the biocontrol potential of EVs from A. pullulans. The EVs did not inhibit the germination of spores of three important phytopathogenic fungi—Botrytis cinerea, Colletotrichum acutatum, and Penicillium expansum. However, exposure of grown cultures of C. acutatum and P. expansum to A. pullulans EVs resulted in visible changes in morphology of colonies. These preliminary results suggest that EVs may be part of the antagonistic activity of A. pullulans, which is so far only partially understood. Thus, the first isolation and characterization of EVs from A. pullulans provides a starting point for further studies of EVs in the biotechnologically important traits of the biocontrol black fungus A. pullulans in particular and in the biological role of fungal EVs in general.
The allogeneic shell technique for alveolar ridge augmentation: a multicenter case series and experiences of more than 300 cases
Authors: Kämmerer Peer W. , Tunkel Jochen , Götz Werner , Würdinger Robert , Kloss Frank , Pabst Andreas
Published: November 2022

Purpose

Allogeneic cortical bone plates (CP) might be used for alveolar ridge augmentation as an alternative to autogenous grafts (AG) and bone substitutes (BS). We report about a multicenter case series and our experiences of more than 300 cases using CP and the shell technique for reconstruction of the alveolar process to illustrate surgical key steps, variations, and complication management.

Methods

Different types of alveolar ridge defects were augmented using the shell technique via CP. The space between the CP and the alveolar bone was filled with either autogenous or allogeneic granules (AUG, ALG) or a mixture of both. Implants were placed after 4–6 months. Microscopic and histological assessments were performed. In addition, space filling using AUG, ALG and bovine BS was discussed.

Results

Scanning electron microscopy demonstrated the compact cortical structure of CP and the porous structure of ALG allowing micro-vessel ingrowth and bone remodeling. Histological assessment demonstrated sufficient bone remodeling and graft resorption after 4–6 months. In total, 372 CP cases and 656 implants were included to data analysis. The mean follow-up period was about 3.5 years. Four implants failed, while all implant failures were caused by peri-implantitis. Next, 30 CP complications were seen, while in 26 CP complications implant placement was possible. CP rehydration, stable positioning by adjusting screws, smoothing of sharp edges, and a tension-free wound closure were identified as relevant success factors. Space filling using ALG and a mixture of AUG/ALG resulted in sufficient bone remodeling, graft resorption and stability of the augmented bone.

Conclusions

CP and the shell technique is appropriate for alveolar ridge augmentation with adequate bone remodeling and low complication rates. Allografts can prevent donor site morbidity and therefore may decrease discomfort for the patient.
Functional tooth number in the posterior region associated serum ucOC levels
Authors: Nakamura Masahiko , Kondo Yusuke , Nakamoto Tetsuji , Nakagawa Aonuma Fumiko , Nodai Tomotaka , Munemasa Takashi , Mukaibo Taro , Masaki Chihiro , Hosokawa Ryuji
Published: November 2022

Purpose

The purpose of this study was to investigate serum undercarboxylated osteocalcin (ucOC) levels in partially edentulous patients scheduled to receive implant treatment and determine the association between ucOC levels, vegetable intake, vitamin K, dietary fiber intake, and functional tooth number in the posterior region (p-FTN).

Methods

A total of 46 patients (20 male and 26 female, 61.9 ± 12.7 years old) were included. The association among serum ucOC levels, vegetable intake, vitamin K and dietary fiber intake was assessed using Spearman’s rank correlation coefficient and binary logistic regression analysis.

Results

In total, 35% of patients (16/46 subjects) showed an abnormally high ucOC level (≧ 4.5 ng/mL). p-FTN showed a weak positive correlation with vegetable intake, vitamin K and dietary fiber intake (r = 0.28, 0.21, and 0.14, respectively) and a significant negative correlation with ucOC levels (r = − 0.51). Multivariate analysis demonstrated that p-FTN as well as vitamin K intake showed a significant negative association with serum ucOC levels.

Conclusions

More than one-third of patients showed abnormally high ucOC levels. p-FTN showed a negative association with serum ucOC levels, which indicated the possibility that oral status affected bone quality.
Extracellular vesicles in the pathogenesis and treatment of acute lung injury
Authors: Hu Qian , Zhang Shu , Yang Yue , Yao Jia-Qi , Tang Wen-Fu , Lyon Christopher J. , Hu Tony Ye , Wan Mei-Hua
Published: November 2022

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common life-threatening lung diseases associated with acute and severe inflammation. Both have high mortality rates, and despite decades of research on clinical ALI/ARDS, there are no effective therapeutic strategies. Disruption of alveolar-capillary barrier integrity or activation of inflammatory responses leads to lung inflammation and injury. Recently, studies on the role of extracellular vesicles (EVs) in regulating normal and pathophysiologic cell activities, including inflammation and injury responses, have attracted attention. Injured and dysfunctional cells often secrete EVs into serum or bronchoalveolar lavage fluid with altered cargoes, which can be used to diagnose and predict the development of ALI/ARDS. EVs secreted by mesenchymal stem cells can also attenuate inflammatory reactions associated with cell dysfunction and injury to preserve or restore cell function, and thereby promote cell proliferation and tissue regeneration. This review focuses on the roles of EVs in the pathogenesis of pulmonary inflammation, particularly ALI/ARDS.
Immune checkpoint inhibitor therapy and elevated levels of C-reactive protein associated with COVID-19 aggravation in patients with lung cancer
Authors: Maki Masatoshi , Takada Ryo , Taniguchi Akihiko , Nomura Naoyuki , Kuramoto Seiichiro , Chiko Yuki , Okada Toshiaki , Saito Seiji , Tamura Koji
Published: November 2022

Background

COVID-19 has become a significant health threat and a primary healthcare concern among the most vulnerable patients with cancer. Patients with COVID-19 who have lung cancer are at great risk and need careful monitoring if they are affected. This study aimed to investigate the clinical characteristics of COVID-19-positive patients with lung cancer and the risks associated with anticancer medication.

Methods

This study was a single-center, retrospective cohort study. Patients with lung cancer who presented with COVID-19 during hospitalization were divided into two groups: those who presented with respiratory failure and those who did not. The patient's background, clinical laboratory values, and anticancer drugs used for therapy were investigated to identify risk factors for respiratory failure.

Results

Thirty-one patients were included in the study; 18 (58.1%) were in the respiratory failure group and 13 (41.9%) were in the group without respiratory failure. In the respiratory failure group, there was a significant difference in using immune checkpoint inhibitor (ICI) use within 90 days (p = 0.025) and the level of C-reactive protein (CRP) level (p = 0.017). The analysis of the operating characteristic of the receiver revealed a cutoff value of 2.75 mg/dL for CRP (area under the curve = 0.744, sensitivity 0.611, specificity 0.923).

Conclusions

A history of ICI within 90 days and elevated CRP (≥ 2.75 mg/dL) levels are potential factors leading to respiratory failure in COVID-19-affected patients undergoing chemotherapy for lung cancer.
Some Japanese mothers do not follow package instructions of infant formula: a web-based analytical cross-sectional study
Authors: Endoh Kaori
Published: November 2022

Background:

Not following the infant formula package instruction endangers infant health. Although infant formula misuse has been reported abroad, its incidence in Japan remains unknown. Furthermore, it is reasonable to assume that experience in childcare reduces the likelihood of making mistakes in using infant formula. This study aimed to examine the association between compliance with infant formula package instruction and childcare experience in Tokyo and surrounding prefectures in Japan.

Methods:

Using a web-based questionnaire, mothers with infants were analyzed cross-sectionally and surveyed regarding their infants’ nutrition and formula preparation methods in August 2021. Compliance with the infant formula package was determined according to (a) using unlabeled infant formula, (b) preparing infant formula without reading package instructions, (c) giving formula to children ≥ 2 h after preparing, and (d) adding other ingredients to the formula bottle. The association between the misuse of infant formula and childcare experience was examined by grouping the participants by infant age (< 6 months and ≥ 6 months), and by comparing first-born child status with later-born. Of the 333 mothers with infants, 3 were excluded due to out-of-scope responses, and 330 were included in the analysis.

Results:

The major sources of information on infant feeding methods among the participants were obstetric facilities (92.1%), internet (36.1%), and family (20.9%). The proportions of participants using infant formulas not labeled as “infant formula,” such as follow-up milk, not preparing at prescribed concentrations, feeding infant formulas > 2 h after preparation, and adding additional ingredients to the bottle were 7.9%, 4.1%, 23.1%, and 15.9%, respectively, which suggest the misuse of infant formula. These four answers did not differ significantly between mothers of children aged < 6 months and ≥ 6 months or between those with first-born and later-born children.

Conclusion:

This study suggested that some Japanese mothers do not follow package instructions of infant formula in Japan. The misuse of infant formula may not be related to the length of time spent in childcare or the presence or absence of childcare experience. Providing appropriate information on the correct use of infant formula to all caregivers, regardless of their parenting experience, is required.