bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial Genome of Brugia malayi Microfilariae Isolated From a Clinical Sample
Authors: Qing Xiong , Kulkeaw Kasem , Wongkamchai Sirichit , Tsui Stephen Kwok-Wing
Published: February 2021

Lymphatic filariasis is a neglected parasitic disease that is a leading cause of long-term disability. Information obtained from genome sequencing of filarial worm can help us identify systems in the worm that are likely to be useful for novel drug design. Brugia (B.) malayi is still the only lymphatic-dwelling filarial parasite with a nearly complete, fully annotated, and published genome. However, most previous studies were based on the FR3 strain of B. malayi, which originally was isolated from a human patient, and was adapted to the rodent model, then maintained in laboratories for more than 60 years. It is uncertain whether genetic variation exists, thus, sequencing of clinical isolates of lymphatic dwelling filarial parasites is a high priority. Here, we report for the first time the complete mitochondrial genome of B. malayi microfilariae from clinical isolate. Complete mitochondrial (mt) genome of the microfilariae isolated from a blood sample taken from a Thai subject living in Narathiwat Province, which is an endemic area of brugian filariasis, was assembled with sequencing reads obtained by Illumina sequencing. Gene annotation, phylogenetic analysis and single nucleotide polymorphism (SNP) were deployed. A complete 13,658-bp mt genome of B. malayi microfilaria was obtained, and it shows 68x coverage. Based on gene annotation, the mt genome consists of 12 protein-coding, two rRNA, and 23 tRNA genes. Phylogenetic analysis using all protein sequences of DNA sequences of mt genome or cytochrome c oxidase subunit I (COX1) revealed a close relationship among three lymphatic filariae (i.e., B. timori, zoonotic B. pahangi, and Wuchereria spp.). The SNPs in the COX1 gene can differentiate microfilariae of B. malayi in human from those found in canine. Furthermore, the number, order and transcription, and direction of B. malayi microfilariae mitochondrial genes were the same as those found in the FR3 strain of B. malayi. The comparison on mitochondrial genome of B. malayi could have important implications on the development of a new intervention or vaccine to treat or prevent this disease in endemic areas/regions around the world.
Potential Application of T-Follicular Regulatory Cell Therapy in Transplantation
Authors: Dudreuilh Caroline , Basu Sumoyee , Scottà Cristiano , Dorling Anthony , Lombardi Giovanna
Published: February 2021

Regulatory T cells (Tregs) constitute a small proportion of circulating CD4+T cells that function to maintain homeostasis and prevent autoimmunity. In light of their powerful immunosuppressive and tolerance-promoting properties, Tregs have become an interesting potential candidate for therapeutic use in conditions such as solid organ transplant or to treat autoimmune and inflammatory conditions. Clinical studies have demonstrated the safety of polyclonally expanded Tregs in graft-versus-host disease, type 1 diabetes, and more recently in renal and liver transplantation. However, Tregs are heterogenous. Recent insights indicate that only a small proportion of Tregs, called T follicular regulatory cells (Tfr) regulate interactions between B cells and T follicular helper (Tfh) cells within the germinal center. Tfr have been mainly described in mouse models due to the challenges of sampling secondary lymphoid organs in humans. However, emerging human studies, characterize Tfr as being CD4+CD25+FOXP3+CXCR5+cells with different levels of PD-1 and ICOS expression depending on their localization, in the blood or the germinal center. The exact role they play in transplantation remains to be elucidated. However, given the potential ability of these cells to modulate antibody responses to allo-antigens, there is great interest in exploring translational applications in situations where B cell responses need to be regulated. Here, we review the current knowledge of Tfr and the role they play focusing on human diseases and transplantation. We also discuss the potential future applications of Tfr therapy in transplantation and examine the evidence for a role of Tfr in antibody production, acute and chronic rejection and tertiary lymphoid organs. Furthermore, the potential impact of immunosuppression on Tfr will be explored. Based on preclinical research, we will analyse the rationale of Tfr therapy in solid organ transplantation and summarize the different challenges to be overcome before Tfr therapy can be implemented into clinical practice.
Association Between Serum Lipid Levels and Patients With Primary Angle-Closure Glaucoma in China: A Cross Sectional, Case–Control Study
Authors: Shao Mingxi , Li Yingzhu , Teng Jisen , Li Shengjie , Cao Wenjun
Published: February 2021

Objective: To evaluate the serum lipid levels of patients with primary angle-closure glaucoma (PACG) and to investigate the relationship between serum lipid levels and PACG.

Methods: In this cross-sectional, case–control study, a total of 320 PACG subjects and 242 age- and sex-matched control subjects were recruited. Serum high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (SDLDL-C), triglyceride (TRIG), and cholesterol (CHOL) levels were measured using enzymatic colorimetry. Serum apolipoprotein A (APOA), apolipoprotein B (APOB), apolipoprotein E (APOE), and lipoprotein(a) (LPa) levels were measured by immunoturbidimetry.

Results: The serum LDL-C, TRIG, HDL-C, APOE, LPa, CHOL, APOB, and APOA levels were significantly higher (p < 0.05) in the PACG group than in the control group. Multiple liner regression analyses revealed that there was a statistically correlation between HDL-C levels and mean deviation MD (B = 0.389, P = 0.002, 95% confidence interval [CI] = −1.249 to −0.624); LDL-C levels and MD (B = 0.190, P = 0.019, 95% CI = −5.632 to −1.306); and CHOL levels and MD (B = 0.364, P = 0.27, 95% CI = −7.727 to −1.839). Logistic regression analyses showed that high serum HDL-C (odds ratio [OR] = 11.01, 95% CI = 5.616–21.587), LDL-C (OR = 1.330, 95% CI = 1.079–1.640), SDLDL-C (OR = 1.007, 95% CI = 1.005–1.008), APOA (OR = 13.621, 95% CI = 7.251–25.591), APOB (OR = 2.243, 95% CI = 1.060–4.732), LPa (OR = 0.999, 95% CI = 0.998–1.00), and CHOL (OR = 1.131, 95% CI = 1.005–1.326) levels were significantly associated with PACG.

Conclusions: High serum HDL-C, LDL-C, APOA, APOB, LPa, and CHOL levels were associated with PACG.
The Route of Sucrose Utilization by Streptococcus mutans Affects Intracellular Polysaccharide Metabolism
Authors: Costa Oliveira Bárbara Emanoele , Ricomini Filho Antônio Pedro , Burne Robert A. , Zeng Lin
Published: February 2021

Streptococcus mutans converts extracellular sucrose (Suc) into exopolysaccharides (EPS) by glucosyl-transferase and fructosyl-transferase enzymes and internalizes Suc for fermentation through the phosphotransferase system (PTS). Here, we examined how altering the routes for sucrose utilization impacts intracellular polysaccharide [IPS; glycogen, (glg)] metabolism during carbohydrate starvation. Strain UA159 (WT), a mutant lacking all exo-enzymes for sucrose utilization (MMZ952), and a CcpA-deficient mutant (∆ccpA) were cultured with sucrose or a combination of glucose and fructose, followed by carbohydrate starvation. At baseline (0h), and after 4 and 24h of starvation, cells were evaluated for mRNA levels of the glg operon, IPS storage, glucose-1-phosphate (G1P) concentrations, viability, and PTS activities. A pH drop assay was performed in the absence of carbohydrates at the baseline to measure acid production. We observed glg operon activation in response to starvation (p<0.05) in all strains, however, such activation was significantly delayed and reduced in magnitude when EPS synthesis was involved (p<0.05). Enhanced acidification and greater G1P concentrations were observed in the sucrose-treated group, but mostly in strains capable of producing EPS (p<0.05). Importantly, only the WT exposed to sucrose was able to synthesize IPS during starvation. Contrary to CcpA-proficient strains, IPS was progressively degraded during starvation in ∆ccpA, which also showed increased glg operon expression and greater PTS activities at baseline. Therefore, sucrose metabolism by secreted enzymes affects the capacity of S. mutans in synthesizing IPS and converting it into organic acids, without necessarily inducing greater expression of the glg operon.
Multimodal Retinal Imaging for Detection of Ischemic Stroke
Authors: Zhao Lu , Wang Hui , Yang Xiufen , Jiang Bin , Li Hongyang , Wang Yanling
Published: February 2021

Background: This study aims to evaluate ocular changes in patients with ischemic stroke using multimodal imaging and explore the predictive value of ocular abnormalities for ischemic stroke.

Methods: A total of 203 patients (ischemic stroke group, 62; control group, 141) were enrolled in this study. Basic data from patients, including age; gender; height; weight; history of hypertension, hyperlipidemia, diabetes, alcohol use, and coronary heart disease; and smoking status, were collected. Consequently, Doppler color ultrasound, color fundus photography, and optical coherence tomography (OCT) examinations were conducted. Differences in traditional risk factors and ocular parameters between the two groups were compared, and binary logistic regression was used for multivariate analysis.

Results: The central retinal artery equivalent (CRAE) in the ischemic stroke group was 150.72 ± 20.15 μm and that in the control group was 159.68 ± 20.05 μm. The difference was statistically significant (P = 0.004). Moreover, the subfoveal choroidal thickness (SFChT) in the ischemic stroke group was 199.90 ± 69.27 μm and that in the control group was 227.40 ± 62.20 μm. The difference was statistically significant (P = 0.006). Logistic regression results showed that smoking [odds ratio (OR) = 2.823; 95% confidence interval (95% CI) = 1.477–5.395], CRAE (OR = 0.980; 95% CI = 0.965–0.996), and SFChT (OR = 0.994; 95% CI = 0.989–0.999) are associated with increased risk of ischemic stroke when ocular parameters were combined with traditional risk factors. The area under the receiver operating characteristic (ROC) curve was 0.726, which shows good diagnostic accuracy.

Conclusion: SFChT may be a diagnostic marker for early detection and monitoring of ischemic stroke. Combined with traditional risks, retinal artery diameter, and choroidal thickness, the prediction model can improve ischemic stroke prediction.
Selective H3 Antagonist (ABT-239) Differentially Modifies Cognitive Function Under the Impact of Restraint Stress
Authors: Trofimiuk Emil , Wielgat Przemysław , Car Halina
Published: February 2021

Background: A considerable number of competitive antagonists/inverse agonists of histamine H3 receptor (H3R) have progressed to clinical assessment, with pitolisant approved for the treatment of narcolepsy. H3R, highly expressed in the CNS, is regarded as a relevant target in CNS disorders. At the same time, new compounds including ABT-239 H3R antagonist (ABT; benzonitrile, 4-[2-[2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl]-5-benzofuranyl]-) are continually being tested. The study aimed to test ABT-239 as a prophylactic agent in stress-induced memory impairments.

Methods: Stressed and non-stressed rats were pre-treated with ABT-239 and subsequently subjected to several behavioral tests aimed at assessing the animals’ working and spatial reference memory [Morris water maze (MWM), Barnes maze (BM)], assessing the locomotor function and anxiety-like behavior [Open field (OF), elevated “plus” maze—EPM].

Results: Chronically stressed rats displayed a significant decline in spatial (working and reference) memory. In the MWM test, we observed an improvement in spatial reference memory in stressed animals and a positive after ABT-239 pre-treatment. In the BM test, the effect of ABT-239 administration on spatial memory changed in successive attempts, from negative initially to favorable in subsequent attempts, and negative in the last trial of the test in the control group of rats. However, a beneficial effect is noted in the group of stressed animals, which remained throughout the entire testing period.

Conclusions: Presented findings demonstrate that ABT-239 shows the potential to abolish or prevent restraint stress-induced spatial memory impairments and cognitive deficits. However, in conditions of appetitive modulation, it could increase damage to memory (unstressed animals).
Comparison of Intraoperative Ultrasound B-Mode and Strain Elastography for the Differentiation of Glioblastomas From Solitary Brain Metastases. An Automated Deep Learning Approach for Image Analysis
Authors: Cepeda Santiago , García-García Sergio , Arrese Ignacio , Fernández-Pérez Gabriel , Velasco-Casares María , Fajardo-Puentes Manuel , Zamora Tomás , Sarabia Rosario
Published: February 2021

Background

The differential diagnosis of glioblastomas (GBM) from solitary brain metastases (SBM) is essential because the surgical strategy varies according to the histopathological diagnosis. Intraoperative ultrasound elastography (IOUS-E) is a relatively novel technique implemented in the surgical management of brain tumors that provides additional information about the elasticity of tissues. This study compares the discriminative capacity of intraoperative ultrasound B-mode and strain elastography to differentiate GBM from SBM.

Methods

We performed a retrospective analysis of patients who underwent craniotomy between March 2018 to June 2020 with glioblastoma (GBM) and solitary brain metastases (SBM) diagnoses. Cases with an intraoperative ultrasound study were included. Images were acquired before dural opening, first in B-mode, and then using the strain elastography module. After image pre-processing, an analysis based on deep learning was conducted using the open-source software Orange. We have trained an existing neural network to classify tumors into GBM and SBM via the transfer learning method using Inception V3. Then, logistic regression (LR) with LASSO (least absolute shrinkage and selection operator) regularization, support vector machine (SVM), random forest (RF), neural network (NN), and k-nearest neighbor (kNN) were used as classification algorithms. After the models’ training, ten-fold stratified cross-validation was performed. The models were evaluated using the area under the curve (AUC), classification accuracy, and precision.

Results

A total of 36 patients were included in the analysis, 26 GBM and 10 SBM. Models were built using a total of 812 ultrasound images, 435 of B-mode, 265 (60.92%) corresponded to GBM and 170 (39.8%) to metastases. In addition, 377 elastograms, 232 (61.54%) GBM and 145 (38.46%) metastases were analyzed. For B-mode, AUC and accuracy values of the classification algorithms ranged from 0.790 to 0.943 and from 72 to 89%, respectively. For elastography, AUC and accuracy values ranged from 0.847 to 0.985 and from 79% to 95%, respectively.

Conclusion

Automated processing of ultrasound images through deep learning can generate high-precision classification algorithms that differentiate glioblastomas from metastases using intraoperative ultrasound. The best performance regarding AUC was achieved by the elastography-based model supporting the additional diagnostic value that this technique provides.
A New Proton Therapy Solution Provides Superior Cardiac Sparing Compared With Photon Therapy in Whole Lung Irradiation for Pediatric Tumor Patients
Authors: Sha Xue , Duan Jinghao , Lin Xiutong , Zhu Jian , Zhang Ruohui , Sun Tao , Wang Hui , Meng Xiangjuan , Yin Yong
Published: February 2021

Objective

Whole lung irradiation (WLI) plays a crucial role in local control in pediatric patients with lung metastases and improves patient survival. The intention of this research was to explore the advantage of cardiac sparing between photons and protons during WLI. We also propose a new solution for cardiac sparing with proton techniques.

Methods

Eleven patients with pediatric tumors and pulmonary metastasis treated with 12 Gy WLI (all received volumetric-modulated arc therapy (VMAT)) in our institute between 2010 and 2019 were retrospectively selected. Each patient was replanned with intensity-modulated radiation therapy (IMRT), helical tomotherapy (HT), and two intensity-modulated proton radiotherapy (IMPT) plans (IMPT-1 and IMPT-2). IMPT-1 considered the whole lung as the planning target volume (PTV), utilizing the anteroposterior technique (0/180°). IMPT-2 was a new proton solution that we proposed in this research. This approach considered the unilateral lung as the PTV, and 3 ipsilateral fields were designed for each lung. Then, IMPT-2 was generated by summing two unilateral lung plans. The primary objective was to obtain adequate coverage (95% of the prescription dose to the PTV) while maximally sparing the dose to the heart. The PTV coverage, conformity index (CI), homogeneity index (HI), and dose–volume statistics of the heart and substructures were assessed by means of the averages of each comparison parameter.

Results

All treatment techniques achieved the target volume coverage required by clinical practice. HT yielded the best coverage and homogeneity for the target structure compared with other techniques. The CI from IMRT was excellent. For photon radiation therapy, the HT plan afforded superior dose sparing for the V5, V6, V7, V8, and Dmean of the heart and Dmean of the right ventricle (RV). IMRT displayed the most notable dose reductions in the V9, V10, V11, and V12 of the heart and Dmean of the right atrium (RA). The VMAT plan was the least effective on the heart and substructures. However, compared with photon radiation therapy, IMPT-1 did not show an advantage for heart protection. Interestingly, IMPT-2 provided significant superiority in cardiac sparing, including maximum dose sparing for the V5, V6, V7, V8, V9 and Dmean of the heart and Dmean of the RA, RV, left atrium (LA) and left ventricle (LV) compared to all other techniques.

Conclusions

Considering the complex anatomical relation between target volumes and organs at risk (OARs), IMPT can provide a dose advantage for organs located outside of the target area rather than within or surrounding the area. It is hoped that advances in proton therapy (PT) plan design will lead to further improvements in radiotherapy approaches and provide the best treatment choice for individual patients.
MR-Guided Radiotherapy: The Perfect Partner for Immunotherapy?
Authors: Hörner-Rieber Juliane , Klüter Sebastian , Debus Jürgen , Adema Gosse , Ansems Marleen , Verheij Marcel
Published: February 2021

During the last years, preclinical and clinical studies have emerged supporting the rationale to integrate radiotherapy and immunotherapy. Radiotherapy may enhance the effects of immunotherapy by improving tumor antigen release, antigen presentation, and T-cell infiltration. Recently, magnetic resonance guided radiotherapy (MRgRT) has become clinically available. Compared to conventional radiotherapy techniques, MRgRT firstly allows for daily on-table treatment adaptation, which enables both dose escalation for increasing tumor response and superior sparing of radiosensitive organs-at-risk for reducing toxicity. The current review focuses on the potential of combining MR-guided adaptive radiotherapy with immunotherapy by providing an overview on the current status of MRgRT, latest developments in preclinical and clinical radio-immunotherapy, and the unique opportunities and challenges for MR-guided radio-immunotherapy. MRgRT might especially assist in answering open questions in radio-immunotherapy regarding optimal radiation dose, fractionation, timing of immunotherapy, appropriate irradiation volumes, and response prediction.
Comparison of Radiomic Models Based on Low-Dose and Standard-Dose CT for Prediction of Adenocarcinomas and Benign Lesions in Solid Pulmonary Nodules
Authors: Liu Jieke , Xu Hao , Qing Haomiao , Li Yong , Yang Xi , He Changjiu , Ren Jing , Zhou Peng
Published: February 2021

Objectives

This study aimed to develop radiomic models based on low-dose CT (LDCT) and standard-dose CT to distinguish adenocarcinomas from benign lesions in patients with solid solitary pulmonary nodules and compare the performance among these radiomic models and Lung CT Screening Reporting and Data System (Lung-RADS). The reproducibility of radiomic features between LDCT and standard-dose CT were also evaluated.

Methods

A total of 141 consecutive pathologically confirmed solid solitary pulmonary nodules were enrolled including 50 adenocarcinomas and 48 benign nodules in primary cohort and 22 adenocarcinomas and 21 benign nodules in validation cohort. LDCT and standard-dose CT scans were conducted using same acquisition parameters and reconstruction method except for radiation dose. All nodules were automatically segmented and 104 original radiomic features were extracted. The concordance correlation coefficient was used to quantify reproducibility of radiomic features between LDCT and standard-dose CT. Radiomic features were selected to build radiomic signature, and clinical characteristics and radiomic signature were combined to develop radiomic nomogram for LDCT and standard-dose CT, respectively. The performance of radiomic models and Lung-RADS was assessed by area under curve (AUC) of receiver operating characteristic curve, sensitivity, and specificity.

Results

Shape and first order features, and neighboring gray tone difference matrix features were highly reproducible between LDCT and standard-dose CT. No significant differences of AUCs were found among radiomic signature and nomogram of LDCT and standard-dose CT in both primary and validation cohort (0.915 vs. 0.919 vs. 0.898 vs. 0.909 and 0.976 vs. 0.976 vs. 0.985 vs. 0.987, respectively). These radiomic models had higher specificity than Lung-RADS (all correct P < 0.05), while there were no significant differences of sensitivity between Lung-RADS and radiomic models.

Conclusions

The diagnostic performance of LDCT-based radiomic models to differentiate adenocarcinomas from benign lesions in solid pulmonary nodules were equivalent to that of standard-dose CT. The LDCT-based radiomic model with higher specificity and lower false-positive rate than Lung-RADS might help reduce overdiagnosis and overtreatment of solid pulmonary nodules in lung cancer screening.
Congenital Hypopituitarism During the Neonatal Period: Epidemiology, Pathogenesis, Therapeutic Options, and Outcome
Authors: Bosch i Ara Laura , Katugampola Harshini , Dattani Mehul T.
Published: February 2021

Introduction:Congenital hypopituitarism (CH) is characterized by a deficiency of one or more pituitary hormones. The pituitary gland is a central regulator of growth, metabolism, and reproduction. The anterior pituitary produces and secretes growth hormone (GH), adrenocorticotropic hormone, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, and prolactin. The posterior pituitary hormone secretes antidiuretic hormone and oxytocin.

Epidemiology:The incidence is 1 in 4,000–1 in 10,000. The majority of CH cases are sporadic; however, a small number of familial cases have been identified. In the latter, a molecular basis has frequently been identified. Between 80–90% of CH cases remain unsolved in terms of molecular genetics.

Pathogenesis:Several transcription factors and signaling molecules are involved in the development of the pituitary gland. Mutations in any of these genes may result in CH includingHESX1, PROP1, POU1F1, LHX3, LHX4, SOX2, SOX3, OTX2, PAX6, FGFR1, GLI2, andFGF8. Over the last 5 years, several novel genes have been identified in association with CH, but it is likely that many genes remain to be identified, as the majority of patients with CH do not have an identified mutation.

Clinical manifestations:Genotype-phenotype correlations are difficult to establish. There is a high phenotypic variability associated with different genetic mutations. The clinical spectrum includes severe midline developmental disorders, hypopituitarism (in isolation or combined with other congenital abnormalities), and isolated hormone deficiencies.

Diagnosis and treatment:Key investigations include MRI and baseline and dynamic pituitary function tests. However, dynamic tests of GH secretion cannot be performed in the neonatal period, and a diagnosis of GH deficiency may be based on auxology, MRI findings, and low growth factor concentrations. Once a hormone deficit is confirmed, hormone replacement should be started. If onset is acute with hypoglycaemia, cortisol deficiency should be excluded, and if identified this should be rapidly treated, as should TSH deficiency. This review aims to give an overview of CH including management of this complex condition.
Comparative Phylogeography of Veronica spicata and V. longifolia (Plantaginaceae) Across Europe: Integrating Hybridization and Polyploidy in Phylogeography
Authors: Buono Daniele , Khan Gulzar , von Hagen Klaus Bernhard , Kosachev Petr A. , Mayland-Quellhorst Eike , Mosyakin Sergei L. , Albach Dirk C.
Published: February 2021

Climatic fluctuations in the Pleistocene caused glacial expansion-contraction cycles in Eurasia and other parts of the world. Consequences of these cycles, such as population expansion and subsequent subdivision, have been studied in many taxa at intraspecific population level across much of the Northern Hemisphere. However, the consequences for the potential of hybridization and polyploidization are poorly understood. Here, we investigated the phylogeographic structure of two widespread, closely related species,Veronica spicataandVeronica longifolia, across their European distribution ranges. We assessed the extent and the geographic pattern of polyploidization in both species and hybridization between them. We used genome-scale SNP data to clarify phylogenetic relationships and detect possible hybridization/introgression events. In addition, crossing experiments were performed in different combination betweenV. spicataandV. longifoliaindividuals of two ploidy levels and of different geographic origins. Finally, we employed ecological niche modeling to infer macroclimatic differences between both species and both ploidy levels. We found a clear genetic structure reflecting the geographical distribution patterns in both species, withV. spicatashowing higher genetic differentiation thanV.longifolia. We retrieved significant signals of hybridization and introgression in natural populations from the genetic data and corroborated this with crossing experiments. However, there were no clear phylogeographic patterns and unequivocal macroclimatic niche differences between diploid and tetraploid lineages. This favors the hypothesis, that autopolyploidization has happened frequently and in different regions. The crossing experiments produced viable hybrids when the crosses were made between plants of the same ploidy levels but not in the interploidy crosses. The results suggest that hybridization occurs across the overlapping areas of natural distribution ranges of both species, with apparently directional introgression fromV. spicatatoV. longifolia. Nevertheless, the two species maintain their species-level separation due to their adaptation to different habitats and spatial isolation rather than reproductive isolation.
Development of Attention and Accuracy in Learning a Categorization Task
Authors: Coppens Leonora C. , Postema Christine E. S. , Schüler Anne , Scheiter Katharina , van Gog Tamara
Published: February 2021

Being able to categorize objects as similar or different is an essential skill. An important aspect of learning to categorize is learning to attend to relevant features (i.e., features that determine category membership) and ignore irrelevant features of the to-be-categorized objects. Feature variability across objects of different categories is informative, because it allows inferring the rules underlying category membership. In this study, participants learned to categorize fictitious creatures (i.e., aliens). We measured attention to the aliens during learning using eye-tracking and calculated the attentional focus as the ratio of attention to relevant versus irrelevant features. As expected, participants’ categorization accuracy improved with practice; however, in contrast to our expectations, their attentional focus did not improve with practice. When computing the attentional focus, attention to the aliens’ eyes was disregarded, because while eyes attract a lot of attention, they did not vary across aliens (non-informative feature). Yet, an explorative analysis of attention to eyes suggested that participants’ attentional focus did become somewhat more efficient in that over time they learned to ignore the eyes. Results are discussed in the context of the need for instructional methods to improve attentional focus in learning to categorize.
A Systematic Review of Culturally Responsive Approaches to Child and Adolescent Mental Health Care in Ethiopia
Authors: Meshesha Hana Shewamoltot , Johnson Veronica
Published: February 2021

In 2012/2013, the prevalence of child mental illness was estimated to be between 12 and 25% in Ethiopia. The Federal Ministry of Health is currently considering the implementation of the second national mental health strategy guided by the World Health Organization’s pyramid model for an optimal mix of services. This model states self-care as the fundamental concept and practice that can be facilitated by the formal and informal sectors surrounding an individual. Despite this remarkable move toward endorsing contemporary approaches to mental health services, Ethiopia struggles with a limited number of knowledgeable and skilled mental health professionals. This systematic review aims at identifying the main challenges Ethiopia might face while implementing the pyramid model. We will suggest ways to bridge the gap between the need for child/adolescent trained mental health professionals and training mental health professionals informed with the value of integrating the concepts of the pyramid model into the system of mental health care for Ethiopians. The paper also discusses the importance of integrating the Wellness based mental health approach into mental health professionals’ training as a means of developing a culturally responsive approach to child and adolescent services. This review provides implications for further studies and mental health policy, systems and services in Ethiopia.
What Is Success? A Narrative Review of Research Evaluating Outcomes of Antibiotics Used for Treatment of Clinical Mastitis
Authors: Ruegg Pamela L.
Published: February 2021

Treatment of clinical mastitis is the most common reason that antimicrobials are given to adult dairy cows and careful consideration of treatment protocols is necessary to ensure responsible antimicrobial stewardship. Clinical mastitis is caused by a variety of bacteria which stimulate an immune response that often results in spontaneous bacteriological clearance but can develop into long-term subclinical infections. Use of antimicrobial therapy is most beneficial for cases that are caused by pathogens that have a low rate of spontaneous cure but high rate of therapeutic cure. The purpose of this paper is to review studies that evaluated outcomes of antimicrobial therapy of clinical mastitis. Few studies reported differences in bacteriological cure among treatments and this outcome was rarely associated with clinical outcomes. Return to normal milk appearance was evaluated in most studies but demonstrated little variation and is not a reliable indicator of therapeutic success. Somatic cell count should be measured at quarter-level and will decline gradually after bacteriological clearance. Few researchers have evaluated important clinical outcomes such as post-treatment milk yield or culling. Few differences among approved antimicrobial therapies have been demonstrated and selection of antimicrobial therapy should consider the spectrum of activity relative to etiology.
Aromatic and Sensory Characterization of Maturana Blanca Wines Made with Different Technologies
Authors: Naranjo Ana , Martínez-Lapuente Leticia , Ayestarán Belén , Guadalupe Zenaida , Pérez Irene , Canals Clara , Adell Elena
Published: February 2021

Vitis vinífera L. cv. Maturana Blanca is an autochthonous minor variety recently recovered in the Rioja Qualified Denomination of Origin (D.O.Ca Rioja, Spain) for the production of monovarietal white wines with singular and differentiated characteristics. In this paper, Maturana Blanca wines made with different technologies were analyzed by sensory analysis and aromatic profile by gas chromatography-mass detector. Maturana Blanca wines were characterized by low pH, high acidity, and yellowish tonalities. The compounds that most influenced the aroma of Maturana Blanca wines were those related to fruity (acetates and ethyl esters), floral aromas (2-phenylethanol), and spicy notes (γ-decalactone). These wines were mainly characterized by volatile compounds of fruity aromas of banana and apple. The use of pre-fermentative maceration increased the concentration of ethyl esters and acetates and produced wines with higher odor activity values, indicating a greater aromatic intensity. The aromatic profile of Maturana Blanca wines fermented in oak barrels showed a greater complexity as they were also characterized by the presence of important amounts of furfural, whiskey lactone, and eugenol. The sensory analysis confirmed the results obtained in the aromatic analysis, and described the wines as fresh and balanced in mouth, with notes of acidity and medium to high persistence. These results will contribute to a better knowledge of this white variety.
Evaluation of the Temporal Muscle Thickness as an Independent Prognostic Biomarker in Patients with Primary Central Nervous System Lymphoma
Authors: Furtner Julia , Nenning Karl-Heinz , Roetzer Thomas , Gesperger Johanna , Seebrecht Lukas , Weber Michael , Grams Astrid , Leber Stefan L. , Marhold Franz , Sherif Camillo , Trenkler Johannes , Kiesel Barbara , Widhalm Georg , Asenbaum Ulrika , Woitek Ramona , Berghoff Anna S. , Prayer Daniela , Langs Georg , Preusser Matthias , Wöhrer Adelheid
Published: February 2021

In this study, we assessed the prognostic relevance of temporal muscle thickness (TMT), likely reflecting patient’s frailty, in patients with primary central nervous system lymphoma (PCNSL). In 128 newly diagnosed PCNSL patients TMT was analyzed on cranial magnetic resonance images. Predefined sex-specific TMT cutoff values were used to categorize the patient cohort. Survival analyses, using a log-rank test as well as Cox models adjusted for further prognostic parameters, were performed. The risk of death was significantly increased for PCNSL patients with reduced muscle thickness (hazard ratio of 3.189, 95% CI: 2–097–4.848, p < 0.001). Importantly, the results confirmed that TMT could be used as an independent prognostic marker upon multivariate Cox modeling (hazard ratio of 2.504, 95% CI: 1.608–3.911, p < 0.001) adjusting for sex, age at time of diagnosis, deep brain involvement of the PCNSL lesions, Eastern Cooperative Oncology Group (ECOG) performance status, and methotrexate-based chemotherapy. A TMT value below the sex-related cutoff value at the time of diagnosis is an independent adverse marker in patients with PCNSL. Thus, our results suggest the systematic inclusion of TMT in further translational and clinical studies designed to help validate its role as a prognostic biomarker.
In Vitro and In Vivo Characterization of MCT1 Inhibitor AZD3965 Confirms Preclinical Safety Compatible with Breast Cancer Treatment
Authors: Benyahia Zohra , Blackman Marine C. N. M. , Hamelin Loïc , Zampieri Luca X. , Capeloa Tania , Bedin Marie L. , Vazeille Thibaut , Schakman Olivier , Sonveaux Pierre
Published: February 2021

To survive and proliferate in solid tumors, cancer cells adapt and evolve rapidly in microenvironments where oxygen and substrate bioavailability fluctuates over time and space. This creates metabolic heterogeneity. Cancer cells can further cooperate metabolically, for example by swapping glycolytic end-product lactate for blood-borne glucose. This type of cooperation can be targeted therapeutically, since transmembrane lactate exchanges are facilitated by lactate-proton symporters of the monocarboxylate (MCT) family. Among new drugs, AZD3965 is a first-in-class selective MCT1 inhibitor currently tested in Phase I/II clinical trials for patients with different types of cancers. Because MCT1 can function bidirectionally, we tested here whether and how malignant and nonmalignant cells adapt their metabolism and MCT repertoire when AZD3965 inhibits either lactate import or export. Using breast-associated malignant and nonmalignant cell lines as models, we report that AZD3965 is not directly cytotoxic. In the presence of glucose and glutamine, oxidative cells can survive when lactate uptake is blocked, and proliferating cells compensate MCT1 inhibition by overexpressing MCT4, a specialized facilitator of lactate export. Phenotypic characterization of mice focusing on metabolism, muscle and brain physiology found partial and transient memory retention defect as sole consequence of MCT1 inhibition by AZD3965. We therefore conclude that AZD3965 is compatible with anticancer therapy.
The Protein Secretome Is Altered in Rectal Cancer Tissue Compared to Normal Rectal Tissue, and Alterations in the Secretome Induce Enhanced Innate Immune Responses
Authors: Heeran Aisling B. , Dunne Margaret R. , Morrissey Maria E. , Buckley Croí E. , Clarke Niamh , Cannon Aoife , Donlon Noel E. , Nugent Timothy S. , Durand Michael , Dunne Cara , Larkin John O. , Mehigan Brian , McCormick Paul , Lynam-Lennon Niamh , O’Sullivan Jacintha
Published: February 2021

Locally advanced rectal cancer is treated with neoadjuvant-chemoradiotherapy; however, only ~22% of patients achieve a complete response, and resistance mechanisms are poorly understood. The role of inflammation and immune cell biology in this setting is under-investigated. In this study, we profiled the inflammatory protein secretome of normal (non-cancer) (n = 8) and malignant rectal tissue (n = 12) pre- and post-radiation in human ex vivo explant models and examined the influence of these untreated and treated secretomes on dendritic cell biology (n = 8 for cancer and normal). These resultant profiles were correlated with patient clinical characteristics. Nineteen factors were secreted at significantly higher levels from the rectal cancer secretome when compared to the normal rectal secretome; Flt-1, P1GF, IFN-γ, IL-6, IL-10, CCL20, CCL26, CCL22, CCL3, CCL4, CCL17, GM-CSF, IL-12/IL-23p40, IL-17A, IL-1α, IL-17A/F, IL-1RA, TSLP and CXCL10 (p < 0.05). Radiation was found to have differential effects on normal rectal tissue and rectal cancer tissue with increased IL-15 and CCL22 secretion following radiation from normal rectal tissue explants (p < 0.05), while no significant alterations were observed in the irradiated rectal cancer tissue. Interestingly, however, the irradiated rectal cancer secretome induced the most potent effect on dendritic cell maturation via upregulation of CD80 and PD-L1. Patient’s visceral fat area correlated with secreted factors including CCL20, suggesting that obesity status may alter the tumour microenvironment (TME). These results suggest that radiation does not have a negative effect on the ability of the rectal cancer TME to induce an immune response. Understanding these responses may unveil potential therapeutic targets to enhance radiation response and mitigate normal tissue injury. Tumour irradiation in this cohort enhances innate immune responses, which may be harnessed to improve patient treatment outcome.
Exploitation of a New Short-Term Multimodel Photovoltaic Power Forecasting Method in the Very Short-Term Horizon to Derive a Multi-Time Scale Forecasting System
Authors: Collino Elena , Ronzio Dario
Published: February 2021

The relentless spread of photovoltaic production drives searches of smart approaches to mitigate unbalances in power demand and supply, instability on the grid and ensuring stable revenues to the producer. Because of the development of energy markets with multiple time sessions, there is a growing need of power forecasting for multiple time steps, from fifteen minutes up to days ahead. To address this issue, in this study both a short-term-horizon of three days and a very-short-term-horizon of three hours photovoltaic production forecasting methods are presented. The short-term is based on a multimodel approach and referred to several configurations of the Analog Ensemble method, using the weather forecast of four numerical weather prediction models. The very-short-term consists of an Auto-Regressive Integrated Moving Average Model with eXogenous input (ARIMAX) that uses the short-term power forecast and the irradiance from satellite elaborations as exogenous variables. The methods, applied for one year to four small-scale grid-connected plants in Italy, have obtained promising improvements with respect to refence methods. The time horizon after which the short-term was able to outperform the very-short-term has also been analyzed. The study also revealed the usefulness of satellite data on cloudiness to properly interpret the results of the performance analysis.
Adaptive Weighted Multi-Level Fusion of Multi-Scale Features: A New Approach to Pedestrian Detection
Authors: Xu Yao , Yu Qin
Published: February 2021

Great achievements have been made in pedestrian detection through deep learning. For detectors based on deep learning, making better use of features has become the key to their detection effect. While current pedestrian detectors have made efforts in feature utilization to improve their detection performance, the feature utilization is still inadequate. To solve the problem of inadequate feature utilization, we proposed the Multi-Level Feature Fusion Module (MFFM) and its Multi-Scale Feature Fusion Unit (MFFU) sub-module, which connect feature maps of the same scale and different scales by using horizontal and vertical connections and shortcut structures. All of these connections are accompanied by weights that can be learned; thus, they can be used as adaptive multi-level and multi-scale feature fusion modules to fuse the best features. Then, we built a complete pedestrian detector, the Adaptive Feature Fusion Detector (AFFDet), which is an anchor-free one-stage pedestrian detector that can make full use of features for detection. As a result, compared with other methods, our method has better performance on the challenging Caltech Pedestrian Detection Benchmark (Caltech) and has quite competitive speed. It is the current state-of-the-art one-stage pedestrian detection method.
A Systematic Review of Cybersecurity Risks in Higher Education
Authors: Ulven Joachim Bjørge , Wangen Gaute
Published: February 2021

The demands for information security in higher education will continue to increase. Serious data breaches have occurred already and are likely to happen again without proper risk management. This paper applies the Comprehensive Literature Review (CLR) Model to synthesize research within cybersecurity risk by reviewing existing literature of known assets, threat events, threat actors, and vulnerabilities in higher education. The review included published studies from the last twelve years and aims to expand our understanding of cybersecurity’s critical risk areas. The primary finding was that empirical research on cybersecurity risks in higher education is scarce, and there are large gaps in the literature. Despite this issue, our analysis found a high level of agreement regarding cybersecurity issues among the reviewed sources. This paper synthesizes an overview of mission-critical assets, everyday threat events, proposes a generic threat model, and summarizes common cybersecurity vulnerabilities. This report concludes nine strategic cyber risks with descriptions of frequencies from the compiled dataset and consequence descriptions. The results will serve as input for security practitioners in higher education, and the research contains multiple paths for future work. It will serve as a starting point for security researchers in the sector.
Unravelling the Sequential Interplay of Mutational Mechanisms during Clonal Evolution in Relapsed Pediatric Acute Lymphoblastic Leukemia
Authors: Antić Željko , Lelieveld Stefan H. , van der Ham Cédric G. , Sonneveld Edwin , Hoogerbrugge Peter M. , Kuiper Roland P.
Published: February 2021

Pediatric acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and is characterized by clonal heterogeneity. Genomic mutations can increase proliferative potential of leukemic cells and cause treatment resistance. However, mechanisms driving mutagenesis and clonal diversification in ALL are not fully understood. In this proof of principle study, we performed whole genome sequencing of two cases with multiple relapses in order to investigate whether groups of mutations separated in time show distinct mutational signatures. Based on mutation allele frequencies at diagnosis and subsequent relapses, we clustered mutations into groups and performed cluster-specific mutational profile analysis and de novo signature extraction. In patient 1, who experienced two relapses, the analysis unraveled a continuous interplay of aberrant activation induced cytidine deaminase (AID)/apolipoprotein B editing complex (APOBEC) activity. The associated signatures SBS2 and SBS13 were present already at diagnosis, and although emerging mutations were lost in later relapses, the process remained active throughout disease evolution. Patient 2 had three relapses. We identified episodic mutational processes at diagnosis and first relapse leading to mutations resembling ultraviolet light-driven DNA damage, and thiopurine-associated damage at first relapse. In conclusion, our data shows that investigation of mutational processes in clusters separated in time may aid in understanding the mutational mechanisms and discovery of underlying causes.
Internet of Things for Mental Health: Open Issues in Data Acquisition, Self-Organization, Service Level Agreement, and Identity Management
Authors: Gutierrez Leonardo J. , Rabbani Kashif , Ajayi Oluwashina Joseph , Gebresilassie Samson Kahsay , Rafferty Joseph , Castro Luis A. , Banos Oresti
Published: February 2021

The increase of mental illness cases around the world can be described as an urgent and serious global health threat. Around 500 million people suffer from mental disorders, among which depression, schizophrenia, and dementia are the most prevalent. Revolutionary technological paradigms such as the Internet of Things (IoT) provide us with new capabilities to detect, assess, and care for patients early. This paper comprehensively survey works done at the intersection between IoT and mental health disorders. We evaluate multiple computational platforms, methods and devices, as well as study results and potential open issues for the effective use of IoT systems in mental health. We particularly elaborate on relevant open challenges in the use of existing IoT solutions for mental health care, which can be relevant given the potential impairments in some mental health patients such as data acquisition issues, lack of self-organization of devices and service level agreement, and security, privacy and consent issues, among others. We aim at opening the conversation for future research in this rather emerging area by outlining possible new paths based on the results and conclusions of this work.