bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of treatment with montelukast alone, budesonide/formoterol alone and a combination of both in cough variant asthma
Authors: Yi Fang , Zhan Chen , Liu Baojuan , Li Hu , Zhou Jianmeng , Tang Jiaman , Peng Wen , Luo Wei , Chen Qiaoli , Lai Kefang
Published: October 2022

Background

Whether cysteinyl-leukotriene receptor antagonists (LTRAs) have a similar antitussive effect to inhaled corticosteroids and long-acting β2-agonist (ICS/LABA), and that LTRA plus ICS/LABA is superior to LTRAs alone or ICS/LABA alone in treating cough variant asthma (CVA) remain unclear. This study aimed to investigate and compare the efficacy of montelukast alone, budesonide/formoterol alone and the combination of both in the treatment of CVA.

Methods

Ninety-nine CVA patients were assigned randomly in a 1:1:1 ratio to receive montelukast (M group: 10 mg, once daily), budesonide/formoterol (BF group: 160/4.5 μg, one puff, twice daily), or montelukast plus budesonide/formoterol (MBF group) for 8 weeks. The primary outcomes were changes in the cough visual analogue scale (VAS) score, daytime cough symptom score (CSS) and night-time CSS, and the secondary outcomes comprised changes in cough reflex sensitivity (CRS), the percentage of sputum eosinophils (sputum Eos%) and fractional exhaled nitric oxide (FeNO). CRS was presented with the lowest concentration of capsaicin that induced at least 5 coughs (C5). The repeated measure was used in data analysis.

Results

The median cough VAS score (median from 6.0 to 2.0 in the M group, 5.0 to 1.0 in the BF group and 6.0 to 1.0 in the MBF group, all p < 0.001), daytime CSS (all p < 0.01) and night-time CSS (all p < 0.001) decreased significantly in all three groups after treatment for 8 weeks. Meanwhile, the LogC5 and sputum Eos% improved significantly in all three groups after 8 weeks treatment (all p < 0.05). No significant differences were found in the changes of the VAS score, daytime and night-time CSSs, LogC5 and sputum Eos% among the three groups from baseline to week 8 (all p > 0.05). The BF and MBF groups also showed significant decreases in FeNO after 8 weeks treatment (p = 0.001 and p = 0.008, respectively), while no significant change was found in the M group (p = 0.457). Treatment with MBF for 8 weeks significantly improved the FEV1/FVC as well as the MMEF% pred and decreased the blood Eos% (all p < 0.05).

Conclusions

Montelukast alone, budesonide/formoterol alone and a combination of both were effective in improving cough symptom, decreasing cough reflex sensitivity and alleviating eosinophilic airway inflammation in patients with CVA, and the antitussive effect and anti-eosinophilic airway inflammation were similar.

Trial registration ClinicalTrials.gov, number NCT01404013.
Metabolic engineering enables Bacillus licheniformis to grow on the marine polysaccharide ulvan
Authors: Dutschei Theresa , Zühlke Marie-Katherin , Welsch Norma , Eisenack Tom , Hilkmann Maximilian , Krull Joris , Stühle Carlo , Brott Stefan , Dürwald Alexandra , Reisky Lukas , Hehemann Jan-Hendrik , Becher Dörte , Schweder Thomas , Bornscheuer Uwe T.
Published: October 2022

Background

Marine algae are responsible for half of the global primary production, converting carbon dioxide into organic compounds like carbohydrates. Particularly in eutrophic waters, they can grow into massive algal blooms. This polysaccharide rich biomass represents a cheap and abundant renewable carbon source. In nature, the diverse group of polysaccharides is decomposed by highly specialized microbial catabolic systems. We elucidated the complete degradation pathway of the green algae-specific polysaccharide ulvan in previous studies using a toolbox of enzymes discovered in the marine flavobacterium Formosa agariphila and recombinantly expressed in Escherichia coli.

Results

In this study we show that ulvan from algal biomass can be used as feedstock for a biotechnological production strain using recombinantly expressed carbohydrate-active enzymes. We demonstrate that Bacillus licheniformis is able to grow on ulvan-derived xylose-containing oligosaccharides. Comparative growth experiments with different ulvan hydrolysates and physiological proteogenomic analyses indicated that analogues of the F. agariphila ulvan lyase and an unsaturated β-glucuronylhydrolase are missing in B. licheniformis. We reveal that the heterologous expression of these two marine enzymes in B. licheniformis enables an efficient conversion of the algal polysaccharide ulvan as carbon and energy source.

Conclusion

Our data demonstrate the physiological capability of the industrially relevant bacterium B. licheniformis to grow on ulvan. We present a metabolic engineering strategy to enable ulvan-based biorefinery processes using this bacterial cell factory. With this study, we provide a stepping stone for the development of future bioprocesses with Bacillus using the abundant marine renewable carbon source ulvan.
Isolation and identification of endophytic actinobacteria from Citrullus colocynthis (L.) Schrad and their antibacterial properties
Authors: Ali Aram R. , Bahrami Yadollah , Kakaei Elham , Mohammadzadeh Sara , Bouk Sasan , Jalilian Nastaran
Published: October 2022

Background

Antibiotic resistance poses a major threat to human health globally. Consequently, new antibiotics are desperately required to discover and develop from unexplored habitats to treat life-threatening infections. Microbial natural products (NP) are still remained as primary sources for the discovery of new antibiotics. Endophytic actinobacteria (EA) which are well-known producers of bioactive compounds could provide novel antibiotic against pathogenic bacteria. This research aimed to isolate EA from theCitrullus colocynthisplant and explore the antibacterial properties of their metabolites against pathogenic bacteria.

Results

The healthy samples were collected, dissected and surface-sterilized before cultured on four different selection media at 28 °C. Six endophytic actinobacteria were isolated fromCitrullus colocynthisplant. They were taxonomically classified into two family namelyStreptomycetaceaeandNocardiopsaceae,based on colony morphological features, scanning electron microscope analysis and molecular identification of isolates. This is the first report on the identification of EA formCitrullus colocynthisand their antibacterial activity. The strains generated a chain of vibrio-comma, cubed or cylindrical shaped spores with indenting or smooth surfaces. Three of those were reported as endophytes for the first time. The strain KUMS-C1 showed 98.55% sequence similarity to its closely related strains which constitutes as a novel species/ strain for which the nameNocardiopsis colocynthissp. was proposed for the isolated strain. Five isolated strains had antagonist activity againstS. aureus,P. aeruginosa, andE. coli. Among those, stain KUMS-C6 showed the broadest spectrum of antibacterial activity against all test bacteria, whereas the strain KUMS-C4 had no antibacterial activity.

Conclusions

NPs have a long history of safe and efficient use for development of pharmaceutical products. Our study highlights thatCitrullus colocynthisis an untapped source for the isolation of EA, generating novel and bioactive metabolites by which might lead to discovery of new antibiotic(s). This study reveals the future of new antibiotic developments looks bright against multi-drug resistance diseases by mining under- or unexplored habitats.
Evaluate the immune-related eRNA models and signature score to predict the response to immunotherapy in thyroid carcinoma
Authors: Wu Pu , Shi Jinyuan , Wang Zhiyuan , Sun Wei , Zhang Hao
Published: October 2022

Background

The functional alterations of eRNAs have been reported to be correlated with tumorigenesis. However, the roles of eRNAs in thyroid cancer (THCA) remain still unclear. This study aimed to construct an immune-related eRNA prognostic signature that could effectively predict the survival and prognosis for THCA.

Methods

The Weighted Gene Co-Expression Network Analysis (WGCNA) was performed to identify THCA-specific immune-related hub genes and immune-related eRNAs were obtained using Pearson correlation analysis. Univariate and least absolute shrinkage and selection operator (LASSO) Cox regression were conducted to construct an immune-related eRNA prognostic signature in training cohort, and the predictive capability was verified in test cohort and entire cohort. Kaplan–Meier analysis, principal component analysis (PCA), receiver operating characteristic (ROC) curves, and nomogram were used to validate the risk signature. Furthermore, CIBERSORT, ESTIMATE and ssGSEA were analyzed to explore the tumor immune microenvironment (TIME) of the risk signature, and the response of potential immunotherapeutic were also discussed.

Results

A total of 125 immune-related eRNAs were obtained and 16 immune-related eRNAs were significantly correlated with overall survival (OS). A 9-immune-related eRNA prognostic signature was constructed, and the risk score was identified as an independent predictor. High-risk groups were associated with a poorer OS. Immune microenvironment analysis indicated that low risk score was correlated with higher immuneScore, high immune cell infiltration, and the better response of immunotherapy. Additionally, we also detected 9 immune-related eRNA expression levels in sixty-two matched tumorous and non-tumorous tissues using qRT-PCR analysis.

Conclusion

Our immune-related eRNA risk signature that was an independent prognostic factor was strongly correlated with the immune microenvironment and may be promising for the clinical prediction of prognosis and immunotherapeutic responses in THCA patients.
Promoted CD4+ T cell-derived IFN-γ/IL-10 by photobiomodulation therapy modulates neurogenesis to ameliorate cognitive deficits in APP/PS1 and 3xTg-AD mice
Authors: Wu Xiaolei , Shen Qi , Chang Haocai , Li Junyu , Xing Da
Published: October 2022

Background

The immune system has been implicated in synaptic plasticity, inflammation, and the progression of Alzheimer's disease (AD). However, there were few studies on improving the niche microenvironment of neural stem cells (NSCs) in the brain of AD to promote adult hippocampal neurogenesis (AHN) by regulating the function of non-parenchymal immune cells.

Methods

The lymph nodes of amyloid precursor protein/presenilin 1 (APP/PS1) and 3xTg (APP/PS1/tau) mouse models of AD were treated with photobiomodulation therapy (PBMT) for 10 J/cm2 per day for 1 month (10 min for each day), T lymphocytes isolated from these two AD models were treated with PBMT for 2 J/cm2 (5 min for each time). The NSCs isolated from hippocampus of these two AD models at E14, and the cells were co-cultivated with PBMT-treated T lymphocyte conditioned medium for NSCs differentiation.

Results

Our results showed that PBMT treatment could promote AHN and reverse cognitive deficits in AD mouse model. The expression of interferon-γ (IFN-γ) and interleukin-10 (IL-10) was upregulated in the brain of these two AD models after PBMT treated, which was induced by the activation of Janus kinase 2 (JAK2)-mediated signal transducer and activator of transcription 4 (STAT4)/STAT5 signaling pathway in CD4+ T cells. In addition, elevated CD4+ T cell levels and upregulated transforming growth factor-β1 (TGFβ1)/insulin-like growth factors-1 (IGF-1)/brain-derived neurotrophic factor (BDNF) protein expression levels were also detected in the brain. More importantly, co-cultivated the PBMT-treated T lymphocyte conditioned medium with NSCs derived from these two AD models was shown to promote NSCs differentiation, which was reflected in the upregulation of both neuronal class-III β-tubulin (Tuj1) and postsynaptic density protein 95 (PSD95), but the effects of PBMT was blocked by reactive oxygen species (ROS) scavenger or JAK2 inhibitor.

Conclusion

Our research suggests that PBMT exerts a beneficial neurogenesis modulatory effect through activating the JAK2/STAT4/STAT5 signaling pathway to promote the expression of IFN-γ/IL-10 in non-parenchymal CD4+ T cells, induction of improvement of brain microenvironmental conditions and alleviation of cognitive deficits in APP/PS1 and 3xTg-AD mouse models.
Exposure to conflict and child health outcomes: evidence from a large multi-country study
Authors: Goli Srinivas , Mavisakalyan Astghik , Rammohan Anu , Vu Loan
Published: October 2022

Background

Previous research has consistently found evidence of poor health outcomes among children living in conflict areas. However, the methodological focus of these studies has largely been on case studies, chart or registry reviews, qualitative studies, and single country studies. This reflects the need for a comprehensive multi-country analysis of the associations between conflicts and child health over a longer period. This study analyses the adverse impact of exposure to different types of conflicts  from in utero to five years of age, on several child health measures across a large group of countries. Our analysis pools data from multiple countries and time-points, to provide robust evidence on the relationship between conflict and child health.

Methods

Geo-referenced data on various forms of conflict are combined with theDemographic Health Surveydataset, to construct a large unique database of 590,488 pre-school age children across 52 developing countries over the period 1997 to 2018. Our analysis exploits the within-country differences in children’s exposure to conflict from in utero to age five, to estimate its association with health outcomes. Our multivariate regression models estimate the links between conflict exposure and child health outcomes, measured using child nutrition outcomes (height-for-age and weight-for-age z-scores) and immunization status.

Results and conclusions

Empirical estimates show that even after controlling for a large array of socio-economic and demographic characteristics and location fixed effects, conflict exposure is negatively associated with child nutrition and immunization, across all our measures of conflict. These findings are robust across a range of specifications, alternative measures of conflict and sub-samples.
Engineering sigma factors and chaperones for enhanced heterologous lipoxygenase production in Escherichia coli
Authors: Pang Cuiping , Zhang Guoqiang , Liu Song , Zhou Jingwen , Li Jianghua , Du Guocheng
Published: October 2022

Background

Lipoxygenase (EC. 1.13.11.12, LOX) can catalyze the addition of oxygen into polyunsaturated fatty acids to produce hydroperoxides, which are widely used in the food, chemical, and pharmaceutical industries. In recent years, the heterologous production of LOX by Escherichia coli has attracted extensive attention. However, overexpressed recombinant LOX in E. coli aggregates and forms insoluble inclusion bodies owing to protein misfolding.

Results

In this study, a split green fluorescent protein-based screening method was developed to screen sigma (σ) factors and molecular chaperones for soluble LOX expression. Three mutant libraries of Skp, GroES, and RpoH was analyzed using the high-throughput screening method developed herein, and a series of mutants with significantly higher yield of soluble heterologous LOX were obtained. The soluble expression level of LOX in the isolated mutants increased by 4.2- to 5.3-fold. Further, the highest LOX activity (up to 6240 ± 269 U·g-DCW−1) was observed in E. coli REopt, with the regulatory factor mutants, RpoH and GroES. Based on RNA-Seq analysis of the selected strains, E. coli Eopt, E. coli Sopt, E. coli Ropt, and wild type, amino acid substitutions in σ factors and molecular chaperones regulated the expression level of genes related to gene replication, recombination, and repair. Furthermore, the regulatory factor mutants were identified to be beneficial to the soluble expression of two other heterologous proteins, amylase and bone morphological protein 12.

Conclusion

In this study, a high-throughput screening method was developed for improved soluble LOX expression. The obtained positive mutants of the regulatory factor were analyzed and employed for the expression of other heterologous proteins, thus providing a potential solution for the inclusion-body protein.
Financial structure, cycle, and instability
Authors: Ninomiya Kenshiro
Published: October 2022

The subprime loan mortgage crisis has revived scholarly interest in Minsky’s financial instability hypothesis. The related mathematical models present two types of Minskian financial structures. We construct macrodynamic models that consider both structures and discuss financial instability and cycles. We also demonstrate that one of the financial cycles occurs when a real factor stabilizes the economy. The burden of interest-bearing debt is an important determinant of the cycle. We posit that the escalating financial fragility in this cycle is a more appropriate interpretation of the Minskian financial structure that refers to hedging, speculative and Ponzi behaviors. We further demonstrate that another financial structure destabilizes the economy. If the instability occurs at the point of fragility, then the economy may deteriorate into financial crisis. Fragility then becomes instability.
Unraveling the structures, functions and mechanisms of epithelial membrane protein family in human cancers
Authors: Zhang Nan , Zhu Hong‑Ping , Huang Wei , Wen Xiang , Xie Xin , Jiang Xian , Peng Cheng , Han Bo , He Gu
Published: October 2022

Peripheral myelin protein 22 (PMP22) and epithelial membrane proteins (EMP-1, -2, and -3) belong to a small hydrophobic membrane protein subfamily, with four transmembrane structures. PMP22 and EMPs are widely expressed in various tissues and play important roles in cell growth, differentiation, programmed cell death, and metastasis. PMP22 presents its highest expression in the peripheral nerve and participates in normal physiological and pathological processes of the peripheral nervous system. The progress of molecular genetics has shown that the genetic changes of the PMP22 gene, including duplication, deletion, and point mutation, are behind various hereditary peripheral neuropathies. EMPs have different expression patterns in diverse tissues and are closely related to the risk of malignant tumor progression. In this review, we focus on the four members in this protein family which are related to disease pathogenesis and discuss gene mutations and post-translational modification of them. Further research into the interactions between structural alterations and function of PMP22 and EMPs will help understand their normal physiological function and role in diseases and might contribute to developing novel therapeutic tools.
Frequency, breed predispositions and other demographic risk factors for diagnosis of hypothyroidism in dogs under primary veterinary care in the UK
Authors: O’Neill Dan G. , Khoo Janine Su Pheng , Brodbelt Dave C. , Church David B. , Pegram Camilla , Geddes Rebecca F.
Published: October 2022

Background

Hypothyroidism is a commonly diagnosed endocrinopathy in dogs. This study aimed to investigate the frequency and risk factors for diagnosis of hypothyroidism in UK primary-care practice. Dogs diagnosed with hypothyroidism were identified by searching electronic patient records of primary-care practices participating in VetCompass. A cohort study design estimated one-year (2016) period prevalence and incidence risk for hypothyroidism. Multivariable binary logistic regression models were used to evaluate associations between demographic risk factors and hypothyroidism.

Results

From 905,553 dogs, 2,105 dogs were recorded with diagnosed hypothyroidism in 2016; 359 incident and 1,746 pre-existing, giving an annual prevalence of 0.23% (95% CI 0.22–0.24) and annual incidence risk of 0.04% (95% CI 0.04–0.04). Multivariable logistic regression identified 24 predisposed and nine protected breeds. Standard Doberman pinscher (odds ratio [OR] = 17.02, 95% CI 12.8–22.64), Tibetan terrier (11.25, 95% CI 8.27–15.32) and boxer (10.44, 95% CI 8.66–12.58) breeds showed high predisposition. Pug (OR 0.29, 95% CI 0.09–0.89), Yorkshire terrier (OR 0.38, 95% CI 0.24–0.59), Shih-tzu (OR 0.38, 95% CI 0.23–0.64) and Jack Russell terrier (OR 0.40, 95% CI 0.29–0.54) were the most protected breeds. Overall, being a purebred dog, being insured, having bodyweight above the breed-sex mean, increasing age, being neutered and rising adult bodyweight also showed increased odds being a dog living with a diagnosis of hypothyroidism.

Conclusions

Several strong breed predispositions for diagnosis of hypothyroidism were identified that can assist with disorder prioritisation in ongoing efforts to improve breed health. Other risk factors were also identified that can assist veterinary surgeons during clinical work-up of suspected cases. Identification of novel evidence for protected breeds provides useful information for research into genetic mechanisms.
Perioperative patient positioning following scalp tumor surgery: an anesthetic challenge
Authors: Kumar Rajnish , Sahay Nishant , Naaz Shagufta , Haq Ansarul , Kumar Rajesh
Published: October 2022

Background

Spindle cell tumors of the scalp are notorious for their potential to present with torrential life-threatening bleeds during surgery and in the postoperative period. We present the successful management of one such case.

Case presentation

A 54-year-old male was operated on for a huge spindle cell tumor of the scalp located in the occipital area. During surgery, blood loss of 2 l was replaced with crystalloids, colloids, and packed red cells. However, during the change of position from prone to supine immediately after surgery, the patient developed sudden and torrential bleeding from the surgical site, leading to asystole and cardiac arrest. The patient was revived and put on postoperative ventilatory support for 1 day in the intensive care unit. He could be discharged successfully without sequelae.

Conclusions

Positioning after surgery of a vascular tumor of the scalp should be gentle, slow, and monitored. Sudden movements predispose patients to secondary hemorrhage, which in scalp tumors could be torrential and life-threatening.
Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary Sjögren syndrome: results of an epidemiologic systematic review/meta-analysis and a consensus guideline from the Brazilian society of rheumatology (hepatic, gastrointestinal and pancreatic)
Authors: Trevisani Virginia Fernandes Moça , Pinheiro Aysa César , de Magalhães Souza Fialho Sonia Cristina , Fernandes Marilena Leal Mesquita Silvestre , Pugliesi Alisson , Pasoto Sandra Gofinet , Lopes Maria Lucia Lemos , Guedes Lissiane Karine Noronha , Miyamoto Samira Tatiyama , dos Santos Laura Caldas , Appenzeller Simone , Fidelix Tania , Ribeiro Sandra Lúcia Euzébio , de Brito Danielle Christinne Soares Egypto , Libório-Kimura Tatiana Nayara , Santos Maria Carmen Lopes Ferreira Silva , Cantali Diego Ustárroz , Gennari Juliana D.’Agostino , Capobianco Karina Gatz , Civile Vinicius Tassoni , Pinto Ana Carolina Pereira Nunes , da Rocha Aline Pereira , Rocha-Filho César Ramos , Oliveira Fabiola Reis , Valim Valeria
Published: October 2022

Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, some systemic manifestations, mainly liver, gastrointestinal, and pancreatic are not routinely evaluated. To address these manifestations, the Sjögren's Syndrome Committee of the Brazilian Society of Rheumatology conducted a broad systematic review of the literature on studies investigating prevalence and diagnosis of these symptoms in Sjogren´s patients and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. This is the second part of this guideline, providing 6 recommendations for liver, gastrointestinal, and pancreatic care of SS patients.
Combatting Fusarium head blight: advances in molecular interactions between Fusarium graminearum and wheat
Authors: Xu Ming , Wang Qinhu , Wang Guanghui , Zhang Xue , Liu Huiquan , Jiang Cong
Published: October 2022

Fusarium head blight (FHB), mainly caused by Fusarium graminearum, is one of the most devastating diseases in wheat and barley worldwide. In addition to causing severe yield losses, F. graminearum produces deoxynivalenol (DON), a trichothecene mycotoxin which is harmful to human health and serves as an important virulence factor. Currently, changes in global climate and tillage systems have made FHB epidemics more frequent and severe. During the past decade, considerable efforts have been deployed to reveal the pathogenic mechanisms of F. graminearum, identify resistance genes in wheat, and breed FHB-resistant varieties. In this review, we highlight recent advances in FHB pathogenesis, F. graminearum-wheat interaction, and wheat defense mechanisms. This review contains four main sections: (1) signal sensing and transduction associated with the pathogenesis of F. graminearum; (2) regulation and functions of DON during wheat infection; (3) roles of F. graminearum-secreted enzymes and effectors in facilitating pathogen infection of wheat; (4) wheat components involved in interactions with F. graminearum. A comprehensive understanding of the molecular interactions between F. graminearum and wheat will contribute to the development of novel and efficient strategies for controlling FHB.
Posterior quadrant epilepsy surgery: case series of a South American hospital
Authors: Velasco Mario , Cárdenas-Cruz Andrés Felipe , Aguilera-Pena María Paula , Vargas-Moreno Alejandro , Nariño Daniel , Pérez Juan Carlos , Zorro Oscar
Published: October 2022

Background

Posterior quadrant epilepsy (PCE) is a type of focal epilepsy that originates in the parietal lobe, occipital lobe, and the parietal-occipital border of the temporal lobe, or in any combination of these regions. PCE has a low incidence, but it can cause a great burden in disability-adjusted life years. In this retrospective cohort, patients of all ages with a diagnosis of PCE between 2006 and 2019 were evaluated in a referral center in Bogotá, Colombia. A descriptive analysis of demographic data, clinical history, imaging findings, type of surgery, histopathological diagnosis, outcome, and follow-up was performed using the Engel scale.

Methods

This study included refractory PCE patients of all ages who were evaluated by the epilepsy surgery group of the Hospital Universitario San Ignacio from 2006 to 2019. Clinical, imaging and surgical variables were obtained from the medical records and analyzed.

Results

Thirteen patients were included in the study, including 8 males and 5 females.  The mean age of diagnosis was 8.8 years, while the mean age of surgery was 25 years. The most frequent clinical finding was intellectual disability. The most common findings on magnetic resonance imaging were encephalomalacia and gliosis. In 61.5% of the patients, the lateralization of video-EEG matched with brain magnetic resonance imaging alteration. The most frequent types of surgery performed were lobectomies, lesionectomies and cortical resections. Seizure-freedom was achieved in approximately one third of the patients; however, more than half of the patients were free of disabling seizures or had significant improvement after surgery.

Conclusions

PCE surgery is scarcely performed worldwide, therefore the effectiveness and outcomes are quite variable in the reported literature. In this study, we show that patients with PCE can obtain great benefits in terms of reduction of seizures with a low risk of surgical complications, encouraging the use of this type of procedure in carefully selected patients.
An efficient approach for anti-jamming in IRNSS receivers using improved PSO based parametric wavelet packet thresholding
Authors: Kambham Jacob Silva Lorraine , Ramarakula Madhu
Published: October 2022

The Indian Regional Navigation Satellite System provides accurate positioning service to the users within and around India, extending up to 1500 km. However, when a receiver encounters a Continuous Wave Interference, its positioning accuracy degrades, or sometimes it even fails to work. Wavelet Packet Transform (WPT) is the most widely used technique for anti-jamming in Global Navigation Satellite System receivers. But the conventional method suffers from threshold drifting and employs inflexible thresholding functions. So, to address these issues, an efficient approach using Improved Particle Swarm Optimization based Parametric Wavelet Packet Thresholding (IPSO-PWPT) is proposed. Firstly, a new parameter adaptive thresholding function is constructed. Then, a new form of inertia weight is presented to enhance the performance of PSO. Later, IPSO is used to optimize the key parameters of WPT. Finally, the implementation of the IPSO-PWPT anti-jamming algorithm is discussed. The performance of the proposed technique is evaluated for various performance metrics in four jamming environments. The evaluation results manifest the proposed method’s efficacy compared to the conventional WPT in terms of anti-jamming capability. Also, the results show the ability of the new thresholding function to process various signals effectively. Furthermore, the findings reveal that the improved PSO outperforms the variants of PSO.
Applying implementation frameworks to the clinical trial context
Authors: Stensland Kristian D. , Sales Anne E. , Damschroder Laura J. , Skolarus Ted A.
Published: October 2022

Background

Clinical trials advance science, benefit society, and provide optimal care to individuals with some conditions, such as cancer. However, clinical trials often fail to reach their endpoints, and low participant enrollment remains a critical problem with trial conduct. In these ways, clinical trials can be considered beneficial evidence-based practices suffering from poor implementation. Prior approaches to improving trials have had difficulties with reproducibility and limited impact, perhaps due to the lack of an underlying trial improvement framework. For these reasons, we propose adapting implementation science frameworks to the clinical trial context to improve the implementation of clinical trials.

Main text

We adapted an outcomes framework (Proctor’s Implementation Outcomes Framework) and a determinants framework (the Consolidated Framework for Implementation Research) to the trial context. We linked these frameworks to ERIC-based improvement strategies and present an inferential process model for identifying and selecting trial improvement strategies based on the Implementation Research Logic Model. We describe example applications of the framework components to the trial context and present a worked example of our model applied to a trial with poor enrollment. We then consider the implications of this approach on improving existing trials, the design of future trials, and assessing trial improvement interventions. Additionally, we consider the use of implementation science in the clinical trial context, and how clinical trials can be “test cases” for implementation research.

Conclusions

Clinical trials can be considered beneficial evidence-based interventions suffering from poor implementation. Adapting implementation science approaches to the clinical trial context can provide frameworks for contextual assessment, outcome measurement, targeted interventions, and a shared vocabulary for clinical trial improvement. Additionally, exploring implementation frameworks in the trial context can advance the science of implementation through both “test cases” and providing fertile ground for implementation intervention design and testing.
The effect of nonlinear loads on the underground distribution cables: a case study
Authors: Elsharkawy Tamer M. Z. , Osman Gomaa F. A. , Salem Waleed A. A.
Published: October 2022

Nonlinear loads have become more prevalent in all applications, including computers, transformers, and adjustable speed drives. The harmonic level of the underground distribution cables rises as a result of these loads. As a result, the cable layers' temperatures are affected by the harmonic levels. The purpose of this paper is to calculate the temperature distribution of a cable conductor and the soil around it under cyclic loading conditions, including the impact of linear and nonlinear loads. The IEC 60,853-2 standard is used to consider the thermal model of an underground cable. The finite element method is investigated to obtain a heat map of the cable layers and their surrounding soil. In this study, the small-scale model was constructed in the laboratory. The cable is installed using two methods at the same loading conditions. The heat transfer in the four-core low-voltage cable installation is measured. Furthermore, total harmonic distortion is measured using a Fluke 125 scope meter. The experimental results from the laboratory model proved that there was an extreme increase in the temperature of cable layers when the cable was installed inside the polyvinyl chloride duct in the soil compared with its installation directly buried in the soil. The results of the experimental tests are compared with simulation results.
Khettaras in the Tafilalet oasis (Morocco): contribution to the promotion of tourism and sustainable development
Authors: Beraaouz Mohamed , Abioui Mohamed , Hssaisoune Mohammed , Martínez-Frías Jesús
Published: October 2022

The khettaras constitute a hydraulic system for mobilising water by gravity from the water table to the surface to irrigate fields in oases. This system, which has been fairly widespread in North Africa, in particular in Algeria (foggara) and Morocco (khettaras), was introduced several centuries ago in the oases of southeastern Morocco and has continued to operate despite various natural and anthropic constraints. Based on these ingenious and millennial hydraulic systems, successive civilisations living in these environments have been able to establish laws and regulations for the management and mobilisation of natural resources, especially water. Indeed, to get the most out of these systems, users have had to abide by rules (Al Orf/Azref) designed to protect, promote, and care for the systems to enhance their sustainability. These hydraulic systems have declined in recent years, notably due to extensive groundwater pumping, climate variability (severe droughts), and the local population’s disinterest for this type of development. Therefore, we have unfortunately witnessed the loss of a thousand-year-old local ancestral know-how that had been developed by different succeeding civilisations in the area. Recent initiatives (2008–2011) have been undertaken by the Moroccan government for the restoration and development of some abandoned khettaras in the Tafilalet Oasis so that they could be utilised in the development of an oasis-based cultural tourism and integrated in a tourist circuit known asMajhoul.This initiative, still in its infancy, has constituted an alternative and a fairly encouraging development for this national and world heritage.
Upconversion nanoparticles for super-resolution quantification of single small extracellular vesicles
Authors: Huang Guan , Liu Yongtao , Wang Dejiang , Zhu Ying , Wen Shihui , Ruan Juanfang , Jin Dayong
Published: October 2022

Although small EVs (sEVs) have been used widely as biomarkers in disease diagnosis, their heterogeneity at single EV level has rarely been revealed. This is because high-resolution characterization of sEV presents a major challenge, as their sizes are below the optical diffraction limit. Here, we report that upconversion nanoparticles (UCNPs) can be used for super-resolution profiling the molecular heterogeneity of sEVs. We show that Er3+-doped UCNPs has better brightness and Tm3+-doped UCNPs resulting in better resolution beyond diffraction limit. Through an orthogonal experimental design, the specific targeting of UCNPs to the tumour epitope on single EV has been cross validated, resulting in the Pearson’s R-value of 0.83 for large EVs and ~ 65% co-localization double-positive spots for sEVs. Furthermore, super-resolution nanoscopy can distinguish adjacent UCNPs on single sEV with a resolution of as high as 41.9 nm. When decreasing the size of UCNPs from 40 to 27 nm and 18 nm, we observed that the maximum UCNPs number on single sEV increased from 3 to 9 and 21, respectively. This work suggests the great potentials of UCNPs approach “digitally” quantify the surface antigens on single EVs, therefore providing a solution to monitor the EV heterogeneity changes along with the tumour progression progress.
Treatment of Cushing Disease With Pituitary-Targeting Seliciclib
Authors: Liu Ning-Ai , Ben-Shlomo Anat , Carmichael John D , Wang Christina , Swerdloff Ronald S , Heaney Anthony P , Barkhoudarian Garni , Kelly Daniel , Noureddin Mazen , Lu Lin , Desai Manish , Stolyarov Yana , Yuen Kevin , Mamelak Adam N , Mirocha James , Tighiouart Mourad , Melmed Shlomo
Published: October 2022

Context

Preclinical studies show seliciclib (R-roscovitine) suppresses neoplastic corticotroph proliferation and pituitary adrenocorticotrophic hormone (ACTH) production.

Objective

To evaluate seliciclib as an effective pituitary-targeting treatment for patients with Cushing disease (CD).

Methods

Two prospective, open-label, phase 2 trials, conducted at a tertiary referral pituitary center, included adult patients with de novo, persistent, or recurrent CD who received oral seliciclib 400 mg twice daily for 4 consecutive days each week for 4 weeks. The primary endpoint in the proof-of-concept single-center study was normalization of 24-hour urinary free cortisol (UFC; ≤ 50 µg/24 hours) at study end; in the pilot multicenter study, primary endpoint was UFC normalization or ≥ 50% reduction in UFC from baseline to study end.

Results

Sixteen patients were consented and 9 were treated. Mean UFC decreased by 42%, from 226.4 ± 140.3 µg/24 hours at baseline to 131.3 ± 114.3 µg/24 hours by study end. Longitudinal model showed significant UFC reductions from baseline to each treatment week. Three patients achieved ≥ 50% UFC reduction (range, 55%-75%), and 2 patients exhibited 48% reduction; none achieved UFC normalization. Plasma ACTH decreased by 19% (P = 0.01) in patients who achieved ≥ 48% UFC reduction. Three patients developed grade ≤ 2 elevated liver enzymes, anemia, and/or elevated creatinine, which resolved with dose interruption/reduction. Two patients developed grade 4 liver-related serious adverse events that resolved within 4 weeks of seliciclib discontinuation.

Conclusion

Seliciclib may directly target pituitary corticotrophs in CD and reverse hypercortisolism. Potential liver toxicity of seliciclib resolves with treatment withdrawal. The lowest effective dose requires further determination.
Metabolomic Profile of Children Conceived With Medically Assisted Technologies
Authors: Tolani Alisha T , Cedars Marcelle I , Zablotska Lydia B , Rinaudo Paolo F
Published: October 2022

Context

Assisted reproductive technologies (ART) and non–in vitro fertilization fertility treatments (NIFT) are treatments for infertility. These technologies may have long-term health effects in children such as increased hypertension, glucose intolerance, and hypertriglyceridemia. Few studies have compared children born following ART and NIFT to those conceived spontaneously by subfertile couples.

Objective

This work aimed to describe metabolic differences in children conceived by ART and NIFT compared to children conceived spontaneously by infertile couples.

Methods

Children conceived by parent(s) receiving infertility care at the University of California, San Francisco, between 2000 and 2017 were invited to participate in the Developmental Epidemiological Study of Children born through Reproductive Technology (DESCRT). Serum metabolomic analyses were conducted using samples from 143 enrolled children (age range 4-12 years, 43% female) conceived using NIFT or ART (with fresh or frozen embryos with and without intracytoplasmic sperm injection [ICSI]) and children conceived spontaneously by subfertile couples. Principal component analysis and multivariable regression were used to compare the distribution of metabolites between groups.

Results

There was no separation in metabolites based on treatment or sex. NIFT-conceived children showed no differences compared to spontaneously conceived controls. Only spontaneously conceived children had different metabolomics profiles from children conceived from fresh ART, frozen ART, and all ICSI. Pantoate and propionylglycine levels were elevated in fresh ART compared to the spontaneous group (P < .001). Propionylglycine levels were elevated in the ICSI (both fresh and frozen) vs the spontaneous group (P < .001). Finally, 5-oxoproline levels were decreased in frozen ART compared to the spontaneous group (P < .001).

Conclusion

NIFT-conceived children did not show any metabolic differences compared with spontaneously conceived children. The metabolic differences between ART-conceived children and children conceived spontaneously were small but unlikely to be clinically significant but should be examined in future studies.
Η ιταλική πολιτική στην Αλβανία και η ελληνική μειονότητα, 1939-1943
Authors: Γιώτης Σπυρίδων
Published: October 2022

Η παρούσα μελέτη αφορά την ελληνική μειονότητα στην Αλβανία κατά την περίοδο 1939-1943. Η έρευνα επικεντρώνεται στην ανάλυση των κοινωνικών προβλημάτων της ελληνικής μειονότητας που προέκυψαν από την ένωση της Αλβανίας με το ιταλικό Βασίλειο, στις συνέπειες του ελληνοϊταλικού πολέμου, καθώς και στον προσδιορισμό των συνθηκών και στη μελέτη των παραγόντων που επηρέασαν τη στάση της ελληνικής μειονότητας απέναντι στον αλβανικό αντιστασιακό αγώνα. Το βασικό επιχείρημα της μελέτης είναι ότι οι πολιτικές και κοινωνικές παράμετροι, μέσα σε ένα περιβάλλον ανασφάλειας, ήταν αποφασιστικής σημασίας για τον πολιτικό προσανατολισμό της μειονότητας. Με βάση την ανάλυση των αρχειακών τεκμηρίων της εποχής, μέρος των οποίων έρχεται στο φως για πρώτη φορά, διερευνάται ο ρόλος της ιταλικής πολιτικής στη διαμόρφωση των σχέσεων της ελληνικής μειονότητας με τους Αλβανούς, τους Ιταλούς και τις ελληνικές αντιστασιακές οργανώσεις, αλλά και ο μηχανισμός πολιτικής ένταξης των μειονοτικών στην αλβανική αντίσταση. Η παρούσα διατριβή φιλοδοξεί να απαντήσει σε όλα εκείνα τα ερωτήματα που οριοθετούν το πλαίσιο, μέσα στο οποίο αποτυπώθηκαν οι κοινές εμπειρίες για την ελληνική μειονότητα. Πρόθεση είναι η καταγραφή των γεγονότων χωρίς την ένταση που προκύπτει από την ομοιογενή σκέψη της εθνικής ιδεολογίας, για την πληρέστερη κατανόηση των εξελίξεων που σηματοδότησαν τις αποφάσεις και τις επιλογές των ανθρώπων της μειονότητας. Από αυτή την άποψη, η έρευνα μπορεί να υπερβεί την κυρίαρχη επίσημη αφήγηση, καθώς βασίζεται σε στοιχεία σημαντικά για ένα ιστορικό ζήτημα, το οποίο εδώ και δεκαετίες έχει σχεδόν αγνοηθεί.
Predictive value of 18F-fluorodeoxyglucose accumulation in visceral fat activity to detect colorectal cancer metastases (prospective observational cohort study)
Authors: Suleimanov Amil , Saduakassova Aigul , Vinnikov Denis , Pokrovsky Vadim , Mamyrbekova Saltanat , Daniyarova Anara , Kozhabek Lyaila
Published: October 2022

Background: To evaluate functional visceral adipose tissue (VAT) activity assessed by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) as a predictive factor of metastases in colorectal cancer (CRC) patients.

Methods: We reviewed study protocols and PET/CT data of 534 CRC patients; 474 patients were subsequently excluded for various reasons. The remaining 60 patients with histologically confirmed adenocarcinoma were then prospectively assessed and were exposed to 18F-FDG PET/CT after a surgical treatment and chemoradiotherapy. Age, histology, stage, and tumor grade data were recorded. Functional VAT activity was verified with maximum standardized uptake value (SUVmax) using 18F-FDG PET/CT and tested as a predictive factor of later metastases in eight subdomains of abdominal regions (RE – epigastric region, RLH – left hypochondriac region, RRL – right lumbar region, RU – umbilical region, RLL – left lumbar region, RRI – right inguinal region, RP – hypogastric (pubic) region, RLI – left inguinal region) and pelvic cavity (P) in the adjusted regression models. In addition, we studied the best areas under the curve (AUC) for SUVmax with the corresponding sensitivity (Se) and specificity (Sp).

Results: In both adjusted for age regression models and receiver operating characteristic (ROC) curve analysis, 18F-FDG accumulation in RLH (cut-off SUVmax 0.74; Se 75%; Sp 61%; AUC 0.668; p=0.049), RU (cut-off SUVmax 0.78; Se 69%; Sp 61%; AUC 0.679; p=0.035), RRL (cut-off SUVmax 1.05; Se 69%; Sp 77%; AUC 0.682; p=0.032) and RRI (cut-off SUVmax 0.85; Se 63%; Sp 61%; AUC 0.672; p=0.043) could predict later metastases in CRC patients, as opposed to age, sex, primary tumor location, tumor grade and histology.

Conclusions: Functional VAT activity was importantly related to later metastases in CRC patients and can be used as their predictive factor.
Case Report: Localized Ewing’s sarcoma of the scapula in an adult
Authors: Elafram Rafik , Ben Romdhane Majdi , Khassairi Nayssem , Ben Rjeb Sarrah , Toumi Saiffallah , Sghaier Majdi
Published: October 2022

Background: Ewing’s sarcoma (ES) of the scapula is a rare entity. It is often discovered late at the metastatic stage of the disease because of its deep location. This neoplasm is common in children and adolescents. We present the first reported case of a localized Ewing’s sarcoma of the scapula in an adult over 40 years-old.

Case presentation: A 48-year-old man presented with left shoulder pain evolving for one year. Physical examination showed a painful, ill-defined swelling of the left shoulder measuring 5 x 3 cm. Magnetic resonance imaging (MRI) was performed showing a mass of the left scapula invading the soft tissues of the shoulder suggestive of a sarcoma. The patient underwent a surgical biopsy finding an ES of the scapula with no secondary localization on the computerized tomography (CT) scan nor on the bone scintigraphy. Neo-adjuvant multiagent chemotherapy was started obtaining a total response. Therefore, the patient underwent a total left scapulectomy. Histopathological examination confirmed the diagnosis of ES with a complete response to chemotherapy. Adjuvant chemotherapy was then indicated. After 3 years of follow-up, no local or distant recurrence was found.

Discussion: ES is a high-grade aggressive lesion that most commonly originates in bone. The ES may affect any bone but is frequent in femur, tibia and ilium, the tumors arising from the scapula comprise fewer than 4% of all ES. No cases of localized Ewing’s sarcoma in adults have been reported to our knowledge. The diagnosis is confirmed by immunohistochemical examination and cytogenic. A multimodal treatment approach including a combination of chemotherapy, surgery, and radiation can modestly improve local tumor outcomes. Metastatic tumors still have poor diagnosis.

Conclusions: ES occurs rarely in adults greater than 20 years-old, and tumors localized in the scapula are even rarer. Histopathology differentiates it from other primary bone/soft tissues tumors.