bluuebunny/crossref_metadata_2025 huggingface dataset:
An integrated image processing approach for 3D scanning and micro-defect detection
Authors: Birla Sandesh , Alya Sachin , Singh Ramesh
Published: October 2022

Restoration of high-value components via additive manufacturing requires autonomous surface scanning and defect identification. The 3D free-form surface can be reconstructed with a point cloud obtained from the scanning. Laser line triangulation-based surface scanning is a promising method for generating a 3D point cloud of the component surface. In this article, a robotic defect scanning system developed using py_openshowvar, an open-source cross-platform communication interface is presented. For effective scanning of micro-scale features with minimal noise, it is crucial to optimize the scanning parameters. The scanner parameters such as exposure time and stand-off distance have been optimized for accurate feature detection. After selecting optimal scanning parameters, a generic algorithm is presented for generating a scanning path for automatic scanning of the 3D parts. Surfaces with pre-fabricated micro-defects are automatically scanned using this algorithm, and an integrated image-processing-based defect identification technique is presented. The geometries obtained from the presented technique were validated using focus variation microscopy, and the results are in good agreement with actual defect geometry, and the measurement error is below 9%.
Novel insights into mouse models of ectopic proplatelet release
Authors: Spindler Markus , Bergmeier Wolfgang , Stradal Theresia E. B. , Zhang Jinyi , Siminovitch Katherine A. , Nicolai Leo , Reinhold Annegret , Bender Markus
Published: October 2022

Mature bone marrow (BM) megakaryocytes (MKs) produce platelets by extending proplatelets into sinusoidal blood vessels. Defects in this process can lead to thrombocytopenia and increased risk of bleeding. Mice lacking the actin-regulatory proteins Profilin 1 (PFN1), Wiskott–Aldrich Syndrome protein (WASp), Actin Related Protein 2/3 complex (Arp2/3), or adhesion and degranulation-promoting adapter protein (ADAP) display thrombocytopenia and ectopic release of (pro)platelet-like particles into the BM compartment, pointing to an important axis of actin-mediated directional proplatelet formation. The mechanism underlying ectopic release in these mice is still not completely understood. However, we hypothesized that similar functional defects account for this observation. We analyzed WASp-, ADAP-, PFN1-, and ARPC2-knockout mice to determine the role of actin reorganization and integrin activation in directional proplatelet formation. ADAP-, ARPC2-, and PFN1-deficient MKs displayed reduced adhesion to collagen, defective F-actin organization, and diminished β1-integrin activation. WASp-deficient MKs showed the strongest reduction in the adhesion assay of collagen and altered F-actin organization with reduced podosome formation. Our results indicate that ADAP, PFN1, WASp, and ARP2/3 are part of the same pathway that regulates polarization processes in MKs and directional proplatelet formation into BM sinusoids.
BRANEnet: embedding multilayer networks for omics data integration
Authors: Jagtap Surabhi , Pirayre Aurélie , Bidard Frédérique , Duval Laurent , Malliaros Fragkiskos D.
Published: October 2022

Background

Gene expression is regulated at different molecular levels, including chromatin accessibility, transcription, RNA maturation, and transport. These regulatory mechanisms have strong connections with cellular metabolism. In order to study the cellular system and its functioning, omics data at each molecular level can be generated and efficiently integrated. Here, we proposeBRANEnet, a novel multi-omics integration framework for multilayer heterogeneous networks.BRANEnetis an expressive, scalable, and versatile method to learn node embeddings, leveraging random walk information within a matrix factorization framework. Our goal is to efficiently integrate multi-omics data to study different regulatory aspects of multilayered processes that occur in organisms. We evaluate our framework using multi-omics data ofSaccharomyces cerevisiae, a well-studied yeast model organism.

Results

We testBRANEneton transcriptomics (RNA-seq) and targeted metabolomics (NMR) data for wild-type yeast strain during a heat-shock time course of 0, 20, and 120 min. Our framework learns features for differentially expressed bio-molecules showing heat stress response. We demonstrate the applicability of the learned features for targeted omics inference tasks: transcription factor (TF)-target prediction, integrated omics network (ION) inference, and module identification. The performance ofBRANEnetis compared to existing network integration methods. Our model outperforms baseline methods by achieving high prediction scores for a variety of downstream tasks.
Predicting potential miRNA-disease associations based on more reliable negative sample selection
Authors: Guo Ruiyu , Chen Hailin , Wang Wengang , Wu Guangsheng , Lv Fangliang
Published: October 2022

Background

Increasing biomedical studies have shown that the dysfunction of miRNAs is closely related with many human diseases. Identifying disease-associated miRNAs would contribute to the understanding of pathological mechanisms of diseases. Supervised learning-based computational methods have continuously been developed for miRNA-disease association predictions. Negative samples of experimentally-validated uncorrelated miRNA-disease pairs are required for these approaches, while they are not available due to lack of biomedical research interest. Existing methods mainly choose negative samples from the unlabelled ones randomly. Therefore, the selection of more reliable negative samples is of great importance for these methods to achieve satisfactory prediction results.

Results

In this study, we propose a computational method termed as KR-NSSM which integrates two semi-supervised algorithms to select more reliable negative samples for miRNA-disease association predictions. Our method uses a refinedK-means algorithm for preliminary screening of likely negative and positive miRNA-disease samples. ARocchioclassification-based method is applied for further screening to receive more reliable negative and positive samples. We implement ablation tests in KR-NSSM and find that the combination of the two selection procedures would obtain more reliable negative samples for miRNA-disease association predictions. Comprehensive experiments based on fivefold cross-validations demonstrate improvements in prediction accuracy on six classic classifiers and five known miRNA-disease association prediction models when using negative samples chose by our method than by previous negative sample selection strategies. Moreover, 469 out of 1123 selected positive miRNA-disease associations by our method are confirmed by existing databases.

Conclusions

Our experiments show that KR-NSSM can screen out more reliable negative samples from the unlabelled ones, which greatly improves the performance of supervised machine learning methods in miRNA-disease association predictions. We expect that KR-NSSM would be a useful tool in negative sample selection in biomedical research.
Untargeted metabolomics analysis reveals Mycobacterium tuberculosis strain H37Rv specifically induces tryptophan metabolism in human macrophages
Authors: Xiao Guohui , Zhang Su , Zhang Like , Liu Shuyan , Li Guobao , Ou Min , Zeng Xuan , Wang Zhaoqin , Zhang Guoliang , Lu Shuihua
Published: October 2022

Background

Tuberculosis (TB) caused byMycobacterium tuberculosis(M. tb) remains a global health issue. The characterized virulentM. tbH37Rv, avirulentM. tbH37Ra and BCG strains are widely used as reference strains to investigate the mechanism of TB pathogenicity. Here, we attempted to determine metabolomic signatures associated with the Mycobacterial virulence in human macrophages through comparison of metabolite profile in THP-1-derived macrophages following exposure to theM. tbH37Rv,M. tbH37Ra and BCG strains.

Results

Our findings revealed remarkably changed metabolites in infected macrophages compared to uninfected macrophages. H37Rv infection specifically induced 247 differentially changed metabolites compared to H37Ra or BCG infection. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed H37Rv specifically induces tryptophan metabolism. Moreover, quantitative PCR (qPCR) results showed that indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2) which converts the tryptophan to a series of biologically second metabolites were up-regulated in H37Rv-infected macrophages compared to H37Ra- or BCG-infected macrophages, confirming the result of enhanced tryptophan metabolism induced by H37Rv infection. These findings indicated that targeting tryptophan (Trp) metabolism may be a potential therapeutic strategy for pulmonary TB.

Conclusions

We identified a number of differentially changed metabolites that specifically induced in H37Rv infected macrophages. These signatures may be associated with the Mycobacterial virulence in human macrophages. The present findings provide a better understanding of the host response associated with the virulence of theMtbstrain.
Time optimization of gadobutrol-enhanced brain MRI for metastases and primary tumors using a dynamic contrast-enhanced imaging
Authors: Seo Jeemin , Lim Changmok , Lee Kye Young , Koh Young-Cho , Moon Won-Jin
Published: October 2022

Background

Recent advances in rapid imaging techniques necessitate the reconsideration of the optimal imaging delay time for contrast-enhanced T1-weighted imaging. The aim of our study was to determine the optimal contrast-enhanced T1-weighted imaging delay time from the obtained time-signal intensity curve (TIC) using gadobutrol in patients with brain metastases, primary brain tumors, and meningiomas.

Methods

This prospective study enrolled 78 patients with brain metastases (n = 39), primary brain tumors (n = 22), or meningiomas (n = 17) who underwent 7-min dynamic contrast-enhanced imaging with single-dose gadobutrol. Based on the time-to-peak (TTP) derived from the TIC, we selected four different time points for analysis. Lesion conspicuity, enhanced rate (ER) and contrast rate (CR) of 116 index lesions were evaluated. Statistical comparisons were made for the four different time points using the Friedman test.

Results

Maximum TTP (305.20 ± 63.47 s) was similar across all three groups (p = 0.342). Lesion conspicuity, CR and ER increased over time in all index lesions; however, no significant difference between the 5- and 7-min images was observed. The longest diameter in all groups differed significantly among time points (p < 0.001); the perpendicular diameter did not differ between the 5- and 7-min images.

Conclusions

Maximum contrast enhancement and lesion conspicuity was achieved 5–7 min after a single gadobutrol injection for brain metastases detection and for primary brain tumor/meningioma evaluation. Acquiring images 5 min after gadobutrol injection is the optimal timing for brain tumor detection during MRI work-up.
A rare case of Immunoglobulin A dominant post-infectious glomerulonephritis (IgA PIGN) in a young patient
Authors: Saghar A. , Klaus G. , Trutnau B. , Kömhoff M. , Gröne H. J. , Weber S.
Published: October 2022

Background

Immunoglobulin A dominant postinfectious glomerulonephritis (IgA PIGN) is a unique medical entity that is rare in the paediatric population. It usually presents with severe renal failure, heavy proteinuria, hypertension, and hypocomplementemia and frequently has an unfavourable prognosis. IgA PIGN generally occurs in association with staphylococcal infections and diabetes mellitus in adult patients. Other pathogens include Escherichia coli and Streptococcus sp. Immunofluorescence studies of kidney biopsy samples show IgA as dominant or codominant antibody.

Case presentation

We encountered a 3-year-old girl with IgA PIGN presenting with acute renal failure, oedema, hypertension, and heavy proteinuria of 7955 mg/g creatinine. Renal biopsy specimens showed diffuse glomerular endocapillary hypercellularity with prominent neutrophil and monocyte infiltration on light microscopy. Strong deposits of IgA and C3 were observed along the glomerular basement membranes and the mesangium by immunofluorescence microscopy, and electron microscopy revealed the presence of subepithelial humps.

The patient was managed with steroid (and probatory antibiotic) therapy and is now undergoing follow-up, with a significant improvement 6 months after the initial presentation (glomerular filtration rate (GFR) and cystatin C clearance rate of 165 ml/min/1.73m2 and 106 ml/min/1.73m2, respectively). No signs of bacterial infection were detectable.

Conclusion

This variant of IgA PIGN must be distinguished from other clinical entities, especially IgA nephropathy (mesangial IgA deposits) and postinfectious glomerulonephritis (C3, IgG and occasional IgM capillary loop deposits with or without mesangial distribution), since patients with IgA PIGN may require steroid treatment in addition to antibiotic therapy. Differential diagnosis should also include C3 glomerulopathy.

IgA PIGN is a recently identified disease entity that generally manifests in adult patients with both IgA and C3 mesangial and glomerular capillary wall deposits. We present a biopsy-proven case of IgA PIGN that manifested in a patient at an exceptionally young age and that has had a good clinical outcome. To the best of our knowledge, this is the youngest IgA PIGN patient reported thus far.
A case of GFAP-IgG positivity followed by anti-NMDAR encephalitis
Authors: Zhang Jia , Gan Jing , Wang Jianjun
Published: October 2022

Background

In recent years, there have been an increasing number of reports on overlapping antibodies in autoimmune encephalitis (AE). There are various types of overlapping antibodies, but the clinical significance of each type is not yet clear. Glial antibodies, such as MOG, AQP4, and especially NMDAR, can be detected in patients with AE. However, little is known about the overlapping antibodies of anti-glial fibrillary acidic protein (GFAP), and only a few case reports have described this overlap.

Case presentation

The patient was a 7-year-old girl with recurrent intermittent fever and seizures, and viral encephalitis was diagnosed at the beginning of the disease. She was discharged after treatment with acyclovir, high-dose immunoglobulins, and valproic acid as an antiseizure medication. Subsequently, the patient still had occasional seizures and abnormal behavior, and the anti-NMDAR antibody test was positive (1:3.2). She was treated with high-dose methylprednisolone and antiseizure therapy. Approximately half a year later, the patient experienced fever and seizures again, serum GFAP IgG was 1:100, and a head MRI indicated new lesions. Improvement was achieved after repeated high-dose methylprednisolone and continuous prednisone anti-inflammatory therapy.

Conclusions

Anti-NMDAR encephalitis combined with GFAP-IgG is uncommon, and repeated tests for AE-associated antibodies may be required in patients with recurrent encephalitis. Compared with cerebrospinal fluid antibody-positive children, serum GFAP IgG-positive children should be comprehensively diagnosed according to their clinical manifestations. It is worth considering whether overlapping antibody syndrome can still be an issue for patients with AE who recover and have negative antibodies after a few months if disease recurrence and new antibodies are detected.
Dietary vitamin A intakes of chinese children with adequate liver stores as assessed by the retinol isotope dilution technique
Authors: Zeng Jing , Li Yanming , Ren Yan , Gu Weiwei , Li Zhaolin , Yang Mei , Xiang Bing
Published: October 2022

Background

We attempted to estimate dietary vitamin A requirements based on dietary vitamin A intake in well-nourished Chinese children with adequate liver vitamin A reserves.

Methods

A cross-sectional study was conducted in a kindergarten and an elementary school in Shiyan city, Hubei province of China from December 2009 to July 2010. After screening, 60 children (22 aged 4 ~ 6 y and 38 aged 7 ~ 9 y) were randomly subjected to a 3-d or 18-d deuterated-retinol-dilution (DRD) procedure to evaluate the vitamin A reserves in the body and liver. Dietary intakes of vitamin A were estimated from two (one in winter and one in summer) consecutive 3-day weighed food records and dietary recalls.

Results

The dietary vitamin A intakes were significantly correlated with vitamin A stores in the body and liver, but not with the serum level of retinol. The dietary vitamin A intakes were 476.9 ± 196.7 µg retinol equivalent (RE) (or 377.7 ± 166.2 µg retinol activity equivalent (RAE)) / day for 4 ~ 6 y children and 529.1 ± 87.2 µg RE/d (or 464.0 ± 81.1 µg RAE/d) for 7 ~ 9 y children with adequate liver vitamin A reserves. The estimated liver stores of vitamin A derived from both time points (3-d and 18-d) were similar.

Conclusion

Adequate dietary vitamin A intakes among the well-nourished Chinese children were estimated to be 477 µg RE/d (95%CI 385 ~ 570) or 378 µg RAE/d (95%CI 304 ~ 441) for 4 ~ 6 y children and 529 µg RE/d (95%CI 500 ~ 560) or 464 µg RAE/d (95%CI 437 ~ 491) for 7 ~ 9 y children. Although it needs to be verified in a larger population of different regions in China, our results provide important data to establish the dietary requirement of vitamin A specifically for Chinese children.
Risk factors of in-home unintentional injuries among 0-6-year-old children in Changsha city of China: a cross-sectional survey based on Bronfenbrenner’s ecological system theory
Authors: Ma Yihan , Song Juan , Hu Ming , Yang Rusi , Yang Panzi
Published: October 2022

Background

In-home unintentional injuries (IUIs) seriously threatened children’s safety. Three factors, including risky behaviors, parental supervision, and home environmental risks, have been identified as major causes for IUIs. Studies considering the interrelations between the three were limited and no relative studies has been carried out among Chinese children. The purpose of this study is to fully explore the influences of behavioral, supervisory and environmental risk factors on IUIs and their associations among Chinese children on the bases of our self-developed scales.

Methods

Through stratified cluster sampling, a cross-sectional survey was conducted with 798 parents of children aged 0 ~ 6 years in Changsha, China. Social demographics and IUIs history in the past year were collected by self-administered questionnaires. Three IUI-related scales, which had been developed and validated by our team, aimed to measure risks from children behavior, parental supervision and in-home environment. Structural equation models were constructed to analyze the relationship of these factors and their influences on IUIs using SPSS 26.0 and AMOS 22.0.

Results

Seven hundred ninety-eight parents were surveyed in total, and 33.58% of them reported with IUIs history of their children. X2/df, goodness-of-fit index (GFI), adjusted goodness-of-fit index (AGFI) and the root-mean-square error of approximation (RMSEA) for the model of the whole children were 4.832, 0.879, 0.856 and 0.069 respectively, indicating an acceptable level of model fit. Direct influences were discovered between risky behaviors and children’s IUIs. Home environmental risks indirectly exerted impacts on IUIs by the mediating effect of risky behaviors, while the significant effect of parental supervision only existed in children aged 4-6 and girls.

Conclusions

Risky behaviors played a mediating role in IUIs among children. Supervision and environmental risks affected IUIs indirectly by the exposure to risky behaviors. Parental supervision may not be able to offset the risks posed by the environmental and behavioral factors, so effective IUIs prevention strategies should focus on behavioral and environmental interventions, with appropriate supervision strategies based on the age and sex characteristics of the child.
Prevalence, awareness, treatment, and control of type 2 diabetes mellitus among the adult residents of tehran: Tehran Cohort Study
Authors: Oraii Alireza , Shafiee Akbar , Jalali Arash , Alaeddini Farshid , Saadat Soheil , Masoudkabir Farzad , Vasheghani-Farahani Ali , Heidari Amirhossein , Sadeghian Saeed , Boroumand Mohamamdali , Karimi Abbasali , H. Franco Oscar
Published: October 2022

Background

The prevalence of type 2 diabetes mellitus has increased in the past decades. We investigated the prevalence of diabetes and its awareness, treatment, and control among adult residents of Tehran.

Methods

We used the recruitment phase data of the Tehran Cohort study, enrolling a random sample of adult residents of Tehran aged ≥35 years. Diabetes was defined as self-report, current use of glucose-lowering medications, and/or fasting plasma glucose (FPG) ≥126mg/dl. Impaired fasting glucose (IFG) was defined as an FPG of 100-125mg/dl. Awareness was defined as diabetes self-report, treatment as receiving glucose-lowering medications, and glycemic control as FPG <126mg/dl. The age- and sex-weighted estimates were calculated using the 2016 national census. Logistic regression models were used to determine the factors associated with diabetes awareness, treatment, and control.

Results

A total of 8151 participants were included. Age- and sex-weighted prevalence of diabetes mellitus and IFG were 16.7% (95% CI: 15.1–18.4) and 25.1% (95% CI: 23.1–27.1), respectively. Diabetes was more prevalent in the eastern and central districts of Tehran. Advanced age (OR per 1-year increase: 1.026, 95% CI: 1.021-1.030), male sex (OR: 1.716, 95% CI: 1.543-1.909), higher BMI levels (OR for BMI ≥35 vs. <20 kg/m2: 4.852, 95% CI: 3.365-6.998), pre-existing hypertension (OR: 1.552, 95% CI: 1.378-1.747), dyslipidemia (OR: 1.692, 95% CI: 1.521-1.883), and chronic kidney disease (OR: 1.650, 95% CI: 1.019-2.673) were associated with an increased odds of diabetes mellitus. On the contrary, diabetes mellitus was less likely in current tobacco (OR: 0.872, 95% CI: 0.765-0.994) and alcohol users (OR: 0.836, 95% CI: 0.703-0.994) compared to non-users. Among diabetic individuals, 82.8% were aware of their condition, 71.9% received treatment, and 31.7% of treated patients had adequate glycemic control. Advanced age and pre-existing comorbidities, including hypertension and dyslipidemia, were associated with higher diabetes awareness and treatment. Furthermore, advanced age, higher levels of education, and female sex were determinants of better glycemic control among treated diabetic participants.

Conclusion

There is a high prevalence of diabetes and IFG among adult residents of Tehran. Additionally, more than two-thirds of treated diabetics living in Tehran remain uncontrolled.
Association of perceived life satisfaction with attitudes toward life-sustaining treatment among the elderly in South Korea: a cross-sectional study
Authors: Yun Il , Kim Hyunkyu , Park Eun-Cheol , Jang Suk-Yong
Published: October 2022

Background

Amidst rapid population aging, South Korea enacted the Well-dying Act, late among advanced countries, but public opinion on the act is not still clear. Against this background, this study aims to: 1) investigate factors affecting elderly individuals’ attitude toward life-sustaining treatment, and 2) examine whether attitude toward life-sustaining treatment is related to their perceived life satisfaction.

Methods

Data from the 2020 Survey of Living Conditions and Welfare Needs of Korean Older Persons were used. There were 9,916 participants (3,971 males; 5,945 females). We used multivariable-adjusted Poisson regression models with robust variance to examine the association between perceived life satisfaction and attitude toward life-sustaining treatment and calculate prevalence ratios (PR) and 95% confidence intervals (CI).

Results

After adjusting potential confounders, the probabilities that the elderly who were dissatisfied with their current life would favor life-sustaining treatment were 1.52 times (95% CI: 1.15–1.64) and 1.28 times (95% CI: 1.09–1.51) higher for men and women, respectively, than the elderly who were satisfied. In addition, attitudes in favor of life-sustaining treatment were observed prominently among the elderly with long schooling years or high household income, when they were dissatisfied with their life.

Conclusions

Our results suggested that for the elderly, life satisfaction is an important factor influencing how they exercise their autonomy and rights regarding dying well and receiving life-sustaining treatment. It is necessary to introduce interventions that would enhance the life satisfaction of the elderly and terminally ill patients and enable them to make their own decisions according to the values of life.
Identifying the presence and severity of dementia by applying interpretable machine learning techniques on structured clinical records
Authors: Vyas Akhilesh , Aisopos Fotis , Vidal Maria-Esther , Garrard Peter , Paliouras Georgios
Published: October 2022

Background

Dementia develops as cognitive abilities deteriorate, and early detection is critical for effective preventive interventions. However, mainstream diagnostic tests and screening tools, such as CAMCOG and MMSE, often fail to detect dementia accurately. Various graph-based or feature-dependent prediction and progression models have been proposed. Whenever these models exploit information in the patients’ Electronic Medical Records, they represent promising options to identify the presence and severity of dementia more precisely.

Methods

The methods presented in this paper aim to address two problems related to dementia: (a) Basic diagnosis: identifying the presence of dementia in individuals, and (b) Severity diagnosis: predicting the presence of dementia, as well as the severity of the disease. We formulate these two tasks as classification problems and address them using machine learning models based on random forests and decision tree, analysing structured clinical data from an elderly population cohort. We perform a hybrid data curation strategy in which a dementia expert is involved to verify that curation decisions are meaningful. We then employ the machine learning algorithms that classify individual episodes into a specific dementia class. Decision trees are also used for enhancing the explainability of decisions made by prediction models, allowing medical experts to identify the most crucial patient features and their threshold values for the classification of dementia.

Results

Our experiment results prove that baseline arithmetic or cognitive tests, along with demographic features, can predict dementia and its severity with high accuracy. In specific, our prediction models have reached an average f1-score of 0.93 and 0.81 for problems (a) and (b), respectively. Moreover, the decision trees produced for the two issues empower the interpretability of the prediction models.

Conclusions

This study proves that there can be an accurate estimation of the existence and severity of dementia disease by analysing various electronic medical record features and cognitive tests from the episodes of the elderly population. Moreover, a set of decision rules may comprise the building blocks for an efficient patient classification. Relevant clinical and screening test features (e.g. simple arithmetic or animal fluency tasks) represent precise predictors without calculating the scores of mainstream cognitive tests such as MMSE and CAMCOG. Such predictive model can identify not only meaningful features, but also justifications of classification. As a result, the predictive power of machine learning models over curated clinical data is proved, paving the path for a more accurate diagnosis of dementia.
IL-10 producing regulatory B cells are decreased in blood from smokers and COPD patients
Authors: Jacobs Merel , Verschraegen Sven , Salhi Bihiyga , Anckaert Jasper , Mestdagh Pieter , Brusselle Guy G. , Bracke Ken R.
Published: October 2022

Background

Two opposing B cell subsets have been defined based on their cytokine profile: IL-6 producing effector B cells (B-effs) versus IL-10 producing regulatory B cells (B-regs) that respectively positively or negatively regulate immune responses. B-regs are decreased and/or impaired in many autoimmune diseases and inflammatory conditions. Since there is increasing evidence that links B cells and B cell-rich lymphoid follicles to the pathogenesis of COPD, the aim of this study was to investigate the presence and function of B-regs in COPD.

Methods

First, presence of IL-10 producing regulatory B cells in human lung tissue was determined by immunohistochemistry. Secondly, quantification of IL-10 + B-regs and IL-6 + B-effs in peripheral blood mononuclear cells (PBMCs) from healthy controls, smokers without airflow limitation, and COPD patients (GOLD stage I-IV) was performed by flow cytometry. Thirdly, we exposed blood-derived B cells from COPD patients in vitro to cigarette smoke extract (CSE) and quantified IL-10 + B-regs and IL-6 + B-effs. Furthermore, we aimed at restoring the perturbed IL10 production by blocking BAFF. Fourthly, we determined mRNA expression of transcription factors involved in IL-10 production in FACS sorted memory- and naive B cells upon exposure to medium or CSE.

Results

The presence of IL-10 producing regulatory B cells in parenchyma and lymphoid follicles in lungs was confirmed by immunohistochemistry. The percentage of IL-10 + B-regs was significantly decreased in blood-derived memory B cell subsets from smokers without airflow limitation and patients with COPD, compared to never smokers. Furthermore, the capacity of B cells to produce IL-10 was reduced upon in vitro exposure to CSE and this could not be restored by BAFF-blockade. Finally, upon CSE exposure, mRNA levels of the transcription factors IRF4 and HIF-1α, were decreased in memory B cells.

Conclusion

Decreased numbers and impaired function of B-regs in smokers and patients with COPD might contribute to the initiation and progression of the disease.
Cognitive and biological effects of citrus phytochemicals in subjective cognitive decline: a 36-week, randomized, placebo-controlled trial
Authors: Galluzzi Samantha , Zanardini Roberta , Ferrari Clarissa , Gipponi Sara , Passeggia Ilaria , Rampini Michela , Sgrò Giovanni , Genovese Salvatore , Fiorito Serena , Palumbo Lucia , Pievani Michela , Frisoni Giovanni B. , Epifano Francesco
Published: October 2022

Background

Auraptene (AUR) and naringenin (NAR) are citrus-derived phytochemicals that influence several biological mechanisms associated with cognitive decline, including neuronal damage, oxidative stress and inflammation. Clinical evidence of the efficacy of a nutraceutical with the potential to enhance cognitive function in cohorts at risk of cognitive decline would be of great value from a preventive perspective. The primary aim of this study is to determine the cognitive effects of a 36-week treatment with citrus peel extract standardized in levels of AUR and NAR in older adults experiencing subjective cognitive decline (SCD). The secondary aim is to determine the effects of these phytochemicals on blood-based biomarkers indicative of neuronal damage, oxidative stress, and inflammation.

Methods

Eighty older persons with SCD will be recruited and randomly assigned to receive the active treatment (400 mg of citrus peel extract containing 0.1 mg of AUR and 3 mg of NAR) or the placebo at a 1:1 ratio for 36 weeks. The primary endpoint is a change in the Repeatable Battery for the Assessment of Neuropsychological Status score from baseline to weeks 18 and 36. Other cognitive outcomes will include changes in verbal and nonverbal memory, attention, executive and visuospatial functions. Blood samples will be collected from a consecutive subsample of 60 participants. The secondary endpoint is a change in interleukin-8 levels over the 36-week period. Other biological outcomes include changes in markers of neuronal damage, oxidative stress, and pro- and anti-inflammatory cytokines.

Conclusion

This study will evaluate whether an intervention with citrus peel extract standardized in levels of AUR and NAR has cognitive and biological effects in older adults with SCD, facilitating the establishment of nutrition intervention in people at risk of cognitive decline.

Trial registration

The trial is registered with the United States National Library of Medicine at the National Institutes of Health Registry of Clinical Trials under the code NCT04744922 on February 9th, 2021 (https://www.clinicaltrials.gov/ct2/show/NCT04744922).
ME-NBI combined with endoscopic ultrasonography for diagnosing and staging the invasion depth of early esophageal cancer: a diagnostic meta-analysis
Authors: Su Feng , Zhu Meiling , Feng Ru , Li Yunhong
Published: October 2022

Background

Several methods can assist in detecting early esophageal cancer (EEC) and staging esophageal cancer (EC) invasion depth.

Objective

To evaluate the accuracy of magnifying endoscopy with narrow-band imaging (ME-NBI) plus endoscopic ultrasonography (EUS) for diagnosing EC.

Methods

We searched the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases for relevant studies. The Quality Assessment of Diagnostic Accuracy Studies 2 (QADAS2) was used to assess the studies’ methodological quality. The sensitivity, specificity, positive likelihood (LR+), negative likelihood (LR−), and diagnostic odds ratio (DOR) were calculated, and the summary receiver operating characteristic (SROC) curves were drawn to evaluate the diagnostic performance.

Results

Seven studies were included. The meta-analysis suggested that the pooled sensitivity, specificity, LR+, LR−, and DOR of ME-NBI plus EUS for diagnosing EC were 0.947 (95% confidence interval [CI], 0.901–0.975), 0.894 (95% CI, 0.847–0.931), 7.989 (95% CI, 4.264–14.970), 0.066 (95% CI, 0.035–0.124), and 137.96 (95% CI, 60.369–315.27), respectively. Those values for staging the invasive depth were 0.791 (95% CI, 0.674–0.881), 0.943 (95% CI, 0.906–0.968), 13.087 (95% CI, 7.559–22.657), 0.226 (95% CI, 0.142–0.360), and 61.332 (95% CI, 27.343–137.57). The areas under the curves (AUCs) for diagnosis and staging were 0.97 and 0.95, respectively.

Conclusions

ME-NBI plus EUS might be an adequate diagnostic and staging modality for EC. Due to the study limitations, more large-scale, high-quality studies are needed to confirm the diagnostic accuracy of ME-NBI plus EUS.
Blood transcriptomics to facilitate diagnosis and stratification in pediatric rheumatic diseases – a proof of concept study
Authors: Ha My Kieu , Bartholomeus Esther , Van Os Luc , Dandelooy Julie , Leysen Julie , Aerts Olivier , Siozopoulou Vasiliki , De Smet Eline , Gielen Jan , Guerti Khadija , De Maeseneer Michel , Herregods Nele , Lechkar Bouchra , Wittoek Ruth , Geens Elke , Claes Laura , Zaqout Mahmoud , Dewals Wendy , Lemay Annelies , Tuerlinckx David , Weynants David , Vanlede Koen , van Berlaer Gerlant , Raes Marc , Verhelst Helene , Boiy Tine , Van Damme Pierre , Jansen Anna C. , Meuwissen Marije , Sabato Vito , Van Camp Guy , Suls Arvid , Werff ten Bosch Jutte Van der , Dehoorne Joke , Joos Rik , Laukens Kris , Meysman Pieter , Ogunjimi Benson
Published: October 2022

Background

Transcriptome profiling of blood cells is an efficient tool to study the gene expression signatures of rheumatic diseases. This study aims to improve the early diagnosis of pediatric rheumatic diseases by investigating patients’ blood gene expression and applying machine learning on the transcriptome data to develop predictive models.

Methods

RNA sequencing was performed on whole blood collected from children with rheumatic diseases. Random Forest classification models were developed based on the transcriptome data of 48 rheumatic patients, 46 children with viral infection, and 35 controls to classify different disease groups. The performance of these classifiers was evaluated by leave-one-out cross-validation. Analyses of differentially expressed genes (DEG), gene ontology (GO), and interferon-stimulated gene (ISG) score were also conducted.

Results

Our first classifier could differentiate pediatric rheumatic patients from controls and infection cases with high area-under-the-curve (AUC) values (AUC = 0.8 ± 0.1 and 0.7 ± 0.1, respectively). Three other classifiers could distinguish chronic recurrent multifocal osteomyelitis (CRMO), juvenile idiopathic arthritis (JIA), and interferonopathies (IFN) from control and infection cases with AUC ≥ 0.8. DEG and GO analyses reveal that the pathophysiology of CRMO, IFN, and JIA involves innate immune responses including myeloid leukocyte and granulocyte activation, neutrophil activation and degranulation. IFN is specifically mediated by antibacterial and antifungal defense responses, CRMO by cellular response to cytokine, and JIA by cellular response to chemical stimulus. IFN patients particularly had the highest mean ISG score among all disease groups.

Conclusion

Our data show that blood transcriptomics combined with machine learning is a promising diagnostic tool for pediatric rheumatic diseases and may assist physicians in making data-driven and patient-specific decisions in clinical practice.
Environmental and health-related research on application and production of rare earth elements under scrutiny
Authors: Klingelhöfer Doris , Braun Markus , Dröge Janis , Fischer Axel , Brüggmann Dörthe , Groneberg David A.
Published: October 2022

Background

Unlike most other commodities, rare earth elements (REEs) are part of a wide range of applications needed for daily life all over the world. These applications range from cell phones to electric vehicles to wind turbines. They are often declared as part of “green technology” and, therefore, often called “green elements”. However, their production and use are not only useful but also risky to the environment and human health, as many studies have shown. Consequently, the range of global research efforts is broad and highly variable, and therefore difficult to capture and assess. Hence, this study aims to assess the global parameters of global research on REE in the context of environment and health (REEeh). In addition to established bibliometric parameters, advanced analyses using market driver and scientific infrastructure values were carried out to provide deep insight into incentives, necessities, and barriers to international research.

Results

The focus of REE research is in line with national aspirations, especially from the major global players, China and the USA. Whereas globally, regional research interests are related to market interests, as evidenced by the inclusion of drivers such as electric vehicles, wind turbines, and permanent magnets. The topics receiving the most attention are related to gadolinium used for magnetic resonance imaging and the use of ceria nanoparticles. Since both are used for medical purposes, the medical research areas are equally profiled and mainly addressed in high-income countries. Nevertheless, environmental issues are increasingly in focus.

Conclusions

There is still a need for research that is independent and open-ended. For this, market-independent technologies, substitutes and recycling of REEs need to be addressed scientifically. The results of this study are relevant for all stakeholders, from individual scientists to planners to funders, to improve future research strategies in line with these research mandates.

Graphical Abstract
Tarsal coalition resections: a long-term retrospective analysis of 97 resections in 78 patients
Authors: Saxena Amol , Allen Ryan , Wright Anthony , Migliorini Filippo , Maffulli Nicola
Published: October 2022

Background

Resection of tarsal coalitions provides good patient satisfaction scores, reduced pain, and improved long-term function in both athletic and non-athletic populations. This study aimed to determine when athletic patients undergoing resection of a tarsal coalition were able to return to their desired activity, and whether they experienced a decreased desired activity level (DDA).

Methods

Data on a total of 78 patients who underwent 97 tarsal coalition resections (49 talocalcaneal coalitions, 47 calcaneo-navicular, 14 cuboid-navicular, and three cuneo-navicular; some patients had more than one coalition) operated between January 2001 and June 2020 were prospectively collected. To subjectively assess outcomes, the Roles and Maudsley score (RM) was utilized.

Results

At an average follow-up from the index procedure of 33.6 ± 41.5 months, return to activity for the entire cohort was 18.3 ± 9.6 weeks. Post-RM was 1.3 ± 0.6.

Conclusion

Surgical excision of tarsal coalitions produced favorable results, with most patients able to return to their desired activity level.

Level of evidence

IV.
Long-term safety and efficacy of gene-corrected autologous keratinocyte grafts for recessive dystrophic epidermolysis bullosa
Authors: So Jodi Y. , Nazaroff Jaron , Iwummadu Chinonso V. , Harris Nicki , Gorell Emily S. , Fulchand Shivali , Bailey Irene , McCarthy Daniel , Siprashvili Zurab , Marinkovich M. Peter , Tang Jean Y. , Chiou Albert S.
Published: October 2022

Background

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating blistering genodermatosis caused by mutations in the COL7A1 gene, which encodes for type VII collagen and is necessary for dermal-epidermal adhesion and integrity. Disease manifestations include severe and debilitating wounds, aggressive squamous cell carcinomas, and premature death; however, there are currently no approved therapies. This Phase 1/2a, open-label study evaluated the long-term efficacy and safety of gene-corrected autologous keratinocyte grafts (EB-101) for chronic RDEB wounds.

Methods

Autologous keratinocytes were harvested from participants with severe RDEB, transduced with a retrovirus containing the full-length COL7A1 gene, and grown into 5 × 7 cm (35 cm2) sheets. Gene-corrected keratinocyte sheets were then transplanted onto chronic RDEB wounds present for ≥ 12 weeks.

Results

Seven adult participants with severe RDEB were grafted with six sheets each (42 total sheets) onto wounds and followed for a mean of 5.9 years (range 4–8 years). Long-term improvements in wound healing and symptoms were observed. At year five, 70% (21/30) of treated sites demonstrated ≥ 50% wound healing compared to baseline by investigator global assessment. No sites with ≥ 50% wound healing were painful or pruritic, compared to 67% (6/9) of sites with < 50% wound healing (p < 0.001) at year five. Grafts were well-tolerated throughout long-term follow-up. No serious adverse events related to treatment were reported over a mean of 5.9 years of follow-up. No persistent systemic autoimmunity against type VII collagen or replication-competent retrovirus infections were identified, and no participants developed squamous cell carcinomas related to treatment during long-term follow-up.

Conclusions

Treatment with EB-101 appears safe and efficacious, and produces long-term improvements in wound healing, pain, and itch for RDEB patients. Results from the Phase 3 randomized controlled trial are forthcoming.

Trial registration

ClinicalTrials.gov, NCT01263379. Registered December 15, 2010. https://clinicaltrials.gov/ct2/show/NCT01263379
The epidemiology and outcomes of prolonged trauma care (EpiC) study: methodology of a prospective multicenter observational study in the Western Cape of South Africa
Authors: Suresh Krithika , Dixon Julia M. , Patel Chandni , Beaty Brenda , del Junco Deborah J. , de Vries Shaheem , Lategan Hendrick J. , Steyn Elmin , Verster Janette , Schauer Steven G. , Becker Tyson E. , Cunningham Cord , Keenan Sean , Moore Ernest E. , Wallis Lee A. , Baidwan Navneet , Fosdick Bailey K. , Ginde Adit A. , Bebarta Vikhyat S. , Mould-Millman Nee-Kofi
Published: October 2022

Background

Deaths due to injuries exceed 4.4 million annually, with over 90% occurring in low-and middle-income countries. A key contributor to high trauma mortality is prolonged trauma-to-treatment time. Earlier receipt of medical care following an injury is critical to better patient outcomes. Trauma epidemiological studies can identify gaps and opportunities to help strengthen emergency care systems globally, especially in lower income countries, and among military personnel wounded in combat. This paper describes the methodology of the “Epidemiology and Outcomes of Prolonged Trauma Care (EpiC)” study, which aims to investigate how the delivery of resuscitative interventions and their timeliness impacts the morbidity and mortality outcomes of patients with critical injuries in South Africa.

Methods

The EpiC study is a prospective, multicenter cohort study that will be implemented over a 6-year period in the Western Cape, South Africa. Data collected will link pre- and in-hospital care with mortuary reports through standardized clinical chart abstraction and will provide longitudinal documentation of the patient’s clinical course after injury. The study will enroll an anticipated sample of 14,400 injured adults. Survival and regression analysis will be used to assess the effects of critical early resuscitative interventions (airway, breathing, circulatory, and neurologic) and trauma-to-treatment time on the primary 7-day mortality outcome and secondary mortality (24-h, 30-day) and morbidity outcomes (need for operative interventions, secondary infections, and organ failure).

Discussion

This study is the first effort in the Western Cape of South Africa to build a standardized, high-quality, multicenter epidemiologic trauma dataset that links pre- and in-hospital care with mortuary data. In high-income countries and the U.S. military, the introduction of trauma databases and registries has led to interventions that significantly reduce post-injury death and disability. The EpiC study will describe epidemiology trends over time, and it will enable assessments of how trauma care and system processes directly impact trauma outcomes to ultimately improve the overall emergency care system.

Trial Registration: Not applicable as this study is not a clinical trial.
Role of ursodeoxycholic acid in neonatal indirect hyperbilirubinemia: a systematic review and meta-analysis of randomized controlled trials
Authors: Lazarus Glen , Francie Jerrell , Roeslani Rosalina Dewi , Saldi Siti Rizny Fitriana , Oswari Hanifah
Published: October 2022

Background

Neonatal jaundice is a transitional phenomenon affecting three out of five full-term newborns globally. Ursodeoxycholic acid could be beneficial in neonatal jaundice needing phototherapy. 

Methods

We searched PubMed, EBSCO, ProQuest, and Cochrane Library up to August 21st, 2021, for articles to be reviewed. Meta-analysis using random-effects model was performed.

Results

Eight studies involving 1116 neonates were chosen in this review; however, only five studies were included for meta-analysis. Phototherapy duration was significantly lower in the interventional group with high heterogeneities. Subgroup analysis of the phototherapy duration based on the risk of bias resulted in a shorter duration (mean difference (MD) = –17.82; 95% CI = –20.17 to –15.47; p =  < 0.001) with low heterogeneity in the treatment group. Secondary outcome focusing on mean total serum bilirubin showed a lower mean total serum bilirubin in 48 h post-treatment (MD = –0.43; 95% CI = –0.64 to –0.22; p =  < 0.0001) with low heterogeneities in Asian countries.”

Conclusions

Ursodeoxycholic acid might be considered as a novel adjuvant therapy in neonatal indirect hyperbilirubinemia to shorten the phototherapy duration and lower the mean total serum bilirubin.