bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Analysis of Targets for Post-Transcriptional Regulation by Rsm Proteins in Pseudomonas putida
Authors: Huertas-Rosales Óscar , Romero Manuel , Chan Kok-Gan , Hong Kar-Wai , Cámara Miguel , Heeb Stephan , Barrientos-Moreno Laura , Molina-Henares María Antonia , Travieso María L. , Ramos-González María Isabel , Espinosa-Urgel Manuel
Published: February 2021

Post-transcriptional regulation is an important step in the control of bacterial gene expression in response to environmental and cellular signals. Pseudomonas putida KT2440 harbors three known members of the CsrA/RsmA family of post-transcriptional regulators: RsmA, RsmE and RsmI. We have carried out a global analysis to identify RNA sequences bound in vivo by each of these proteins. Affinity purification and sequencing of RNA molecules associated with Rsm proteins were used to discover direct binding targets, corresponding to 437 unique RNA molecules, 75 of them being common to the three proteins. Relevant targets include genes encoding proteins involved in signal transduction and regulation, metabolism, transport and secretion, stress responses, and the turnover of the intracellular second messenger c-di-GMP. To our knowledge, this is the first combined global analysis in a bacterium harboring three Rsm homologs. It offers a broad overview of the network of processes subjected to this type of regulation and opens the way to define what are the sequence and structure determinants that define common or differential recognition of specific RNA molecules by these proteins.
Early Treatment Initiation With Oral Prednisolone for Relapse Prevention Alleviates Depression and Fatigue in Aquaporin-4–Positive Neuromyelitis optica Spectrum Disorder
Authors: Akaishi Tetsuya , Takahashi Toshiyuki , Fujihara Kazuo , Misu Tatsuro , Fujimori Juichi , Takai Yoshiki , Nishiyama Shuhei , Abe Michiaki , Ishii Tadashi , Aoki Masashi , Nakashima Ichiro
Published: February 2021

Background:Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing autoimmune-related neurological disorder of the central nervous system. Most patients with NMOSD have serum anti-aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). In addition to optic neuritis and myelitis, other insidious symptoms such as depressive state and chronic fatigue in NMOSD are gradually being recognized.

Methods: To elucidate the impact of low- to medium-dose oral prednisolone (PSL) as a relapse prevention therapy for psychiatric disturbances and chronic fatigue in NMOSD, we evaluated clinical data from 39 patients with AQP4-IgG-positive NMOSD, along with the details of present and cumulative oral PSL dosage.

Results: Thirty-six of the 39 patients were treated with low- to medium-dose oral PSL, and the mean and standard deviation of the present daily dose of oral PSL were 7.9 ± 4.0 mg/day. None of the patients were treated with a daily PSL dose of >15 mg. As a result, the disease duration and the untreated period before starting oral PSL showed weak to moderate correlations with the subsequent severities of psychiatric disturbance and fatigue level. Meanwhile, none of the other treatment-related variables evaluated, such as the present oral PSL daily dose, cumulative PSL dose, months of oral PSL administration, previous courses of steroid pulse therapy, and coadministered immunosuppressants, were correlated with these insidious symptoms.

Conclusion: Our results suggest that the use of long-term low- to medium-dose oral PSL ≤15 mg daily for relapse prevention in AQP4-IgG-positive NMOSD would not aggravate the psychiatric and fatigue conditions. On the contrary, early initiation of oral PSL for relapse prevention, together with significantly decreased relapse rate, alleviated the subsequent depressive state and fatigue from the disease.
CT Angiography-Based Radiomics for Classification of Intracranial Aneurysm Rupture
Authors: Alwalid Osamah , Long Xi , Xie Mingfei , Yang Jiehua , Cen Chunyuan , Liu Huan , Han Ping
Published: February 2021

Background: Intracranial aneurysm rupture is a devastating medical event with a high morbidity and mortality rate. Thus, timely detection and management are critical. The present study aimed to identify the aneurysm radiomics features associated with rupture and to build and evaluate a radiomics classification model of aneurysm rupture.

Methods: Radiomics analysis was applied to CT angiography (CTA) images of 393 patients [152 (38.7%) with ruptured aneurysms]. Patients were divided at a ratio of 7:3 into retrospective training (n = 274) and prospective test (n = 119) cohorts. A total of 1,229 radiomics features were automatically calculated from each aneurysm. The feature number was systematically reduced, and the most important classifying features were selected. A logistic regression model was constructed using the selected features and evaluated on training and test cohorts. Radiomics score (Rad-score) was calculated for each patient and compared between ruptured and unruptured aneurysms.

Results: Nine radiomics features were selected from the CTA images and used to build the logistic regression model. The radiomics model has shown good performance in the classification of the aneurysm rupture on training and test cohorts [area under the receiver operating characteristic curve: 0.92 [95% confidence interval CI: 0.89–0.95] and 0.86 [95% CI: 0.80–0.93], respectively, p < 0.001]. Rad-score showed statistically significant differences between ruptured and unruptured aneurysms (median, 2.50 vs. −1.60 and 2.35 vs. −1.01 on training and test cohorts, respectively, p < 0.001).

Conclusion: The results indicated the potential of aneurysm radiomics features for automatic classification of aneurysm rupture on CTA images.
Pre-treatment of Single and Double Antiplatelet and Anticoagulant With Intravenous Thrombolysis for Older Adults With Acute Ischemic Stroke: The TTT-AIS Experience
Authors: Lin Sheng-Feng , Hu Han-Hwa , Ho Bo-Lin , Chen Chih-Hung , Chan Lung , Lin Huey-Juan , Sun Yu , Lin Yung-Yang , Chen Po-Lin , Lin Shinn-Kuang , Wei Cheng-Yu , Lin Yu-Te , Lee Jiunn-Tay , Chao A-Ching ,   Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) Study Group
Published: February 2021

Background: This study aimed to investigate the safety and efficacy of single antiplatelet, anticoagulant and Dual Antiplatelet pre-treatment (DAPP) in older, moderate to high severity acute ischemic stroke patients treated with intravenous thrombolysis (IVT).

Methods: A prospective cohort study was conducted to monitor the development of symptomatic intracranial hemorrhage (SICH) and functional outcomes at 90 days. Two different dosages of alteplase were used for IVT. Logistic regression models were used for analysis of the safety and efficacy outcomes.

Results: A total of 1,156 patients were enrolled and categorized into six groups based on their pre-treatment medications: (1) aspirin (n = 213), (2) clopidogrel (n = 37), (3) DAPP of aspirin + clopidogrel (n= 27), (4) warfarin (n = 44), (5) any of the above pre-medications (n = 331), and (6) none of these medications as controls (n = 825). The DAPP group showed significantly increased SICH by the NINDS (adjusted OR: 4.90, 95% CI 1.28–18.69) and the ECASS II (adjusted OR: 5.09, 95% CI: 1.01–25.68) standards. The aspirin group was found to significantly improve the favorable functional outcome of the modified Rankin Scale (mRS) of 0–1 (adjusted OR: 1.91, 95% CI, 1.31.2.78), but no significance for mRS of 0–2 (adjusted OR: 1.39, 95% CI, 0.97–1.99). The DAPP group also significantly increased mortality (adjusted OR: 4.75, 95% CI: 1.77–12.72). A significant interaction between different dosages for IVT and the functional status was noted. Compared to standard dose, the DAPP group showed higher proportions of disability and mortality with low dose of IVT.

Conclusion: For older adults with higher baseline severity of acute ischemic stroke, DAPP may increase the risk of SICH and mortality post IVT. However, DAPP is still not an indication to withdraw IVT and to prescribe low-dose IVT for older adults.
Machine Learning Analytics of Resting-State Functional Connectivity Predicts Survival Outcomes of Glioblastoma Multiforme Patients
Authors: Lamichhane Bidhan , Daniel Andy G. S. , Lee John J. , Marcus Daniel S. , Shimony Joshua S. , Leuthardt Eric C.
Published: February 2021

Glioblastoma multiforme (GBM) is the most frequently occurring brain malignancy. Due to its poor prognosis with currently available treatments, there is a pressing need for easily accessible, non-invasive techniques to help inform pre-treatment planning, patient counseling, and improve outcomes. In this study we determined the feasibility of resting-state functional connectivity (rsFC) to classify GBM patients into short-term and long-term survival groups with respect to reported median survival (14.6 months). We used a support vector machine with rsFC between regions of interest as predictive features. We employed a novel hybrid feature selection method whereby features were first filtered using correlations between rsFC and OS, and then using the established method of recursive feature elimination (RFE) to select the optimal feature subset. Leave-one-subject-out cross-validation evaluated the performance of models. Classification between short- and long-term survival accuracy was 71.9%. Sensitivity and specificity were 77.1 and 65.5%, respectively. The area under the receiver operating characteristic curve was 0.752 (95% CI, 0.62–0.88). These findings suggest that highly specific features of rsFC may predict GBM survival. Taken together, the findings of this study support that resting-state fMRI and machine learning analytics could enable a radiomic biomarker for GBM, augmenting care and planning for individual patients.
Icaritin Alleviates Glutamate-Induced Neuronal Damage by Inactivating GluN2B-Containing NMDARs Through the ERK/DAPK1 Pathway
Authors: Liu Song , Liu Chaoming , Xiong Lijiao , Xie Jiali , Huang Cheng , Pi Rongbiao , Huang Zhihua , Li Liangdong
Published: February 2021

Excitatory toxicity due to excessive glutamate release is considered the core pathophysiological mechanism of cerebral ischemia. It is primarily mediated by N-methyl-D-aspartate receptors (NMDARs) on neuronal membranes. Our previous studies have found that icaritin (ICT) exhibits neuroprotective effects against cerebral ischemia in rats, but the underlying mechanism is unclear. This study aims to investigate the protective effect of ICT on glutamate-induced neuronal injury and uncover its possible molecular mechanism. An excitatory toxicity injury model was created using rat primary cortical neurons treated with glutamate and glycine. The results showed that ICT has neuroprotective effects on glutamate-treated primary cortical neurons by increasing cell viability while reducing the rate of lactate dehydrogenase (LDH) release and reducing apoptosis. Remarkably, ICT rescued the changes in the ERK/DAPK1 signaling pathway after glutamate treatment by increasing the expression levels of p-ERK, p-DAPK1 and t-DAPK1. In addition, ICT also regulates NMDAR function during glutamate-induced injury by decreasing the expression level of the GluN2B subunit and enhancing the expression level of the GluN2A subunit. As cotreatment with the ERK-specific inhibitor U0126 and ICT abolishes the beneficial effects of ITC on the ERK/DAPK1 pathway, NMDAR subtypes and neuronal cell survival, ERK is recognized as a crucial mediator in the protective mechanism of ICT. In conclusion, our findings demonstrate that ICT has a neuroprotective effect on neuronal damage induced by glutamate, and its mechanism may be related to inactivating GluN2B-containing NMDAR through the ERK/DAPK1 pathway. This study provides a new clue for the prevention and treatment of clinical ischemic cerebrovascular diseases.
Age-Related Cognitive Decline and the Olfactory Identification Deficit Are Associated to Increased Level of Depression
Authors: Sanna Fabrizio , Loy Francesco , Piras Raffaella , Moat Alan , Masala Carla
Published: February 2021

Purpose

Previous studies reported a correlation between olfactory function and depression. However, in literature, no data are available for the correlation between depression and all other factors such as age, sex, olfactory, gustatory, and cognitive function in healthy subjects taken together. The aim of this study was to provide a systematic account regarding the association between those variables in a non-clinical population.

Methods

Two hundred and seventy-three participants were recruited with an age range of 19–84 years. Olfactory, gustatory, cognitive function, and depression level were evaluated by means of the following tests: the Sniffin’ Sticks test, Taste Strips test, Montreal Cognitive Assessment (MoCA), and Beck Depression Inventory (BDI).

Results

In our data, an age-related decrease in olfactory and gustatory function and a decline in cognitive functions such as attention, memory, and language were observed. Instead, no significant differences were observed for the depression level in relation to the different age ranges. However, our results indicated that the depression level could be associated to sex, odor identification impairment, and decreased attention and language.

Conclusion

Sex, the odor identification impairment, and an age-related decrease in attention and language are associated with increased level of depression in healthy subjects. Our data can be useful and informative for health care workers, that is, to have adequate preventive strategies to be used whenever these conditions are detected and recognized.
Kefir and Intestinal Microbiota Modulation: Implications in Human Health
Authors: Peluzio Maria do Carmo Gouveia , Dias Mariana de Moura e , Martinez J. Alfredo , Milagro Fermín I.
Published: February 2021

In the last decades changes in the pattern of health and disease in Latin America and in the world has been observed, with an increase in cases of chronic non-communicable diseases. Changes in intestinal microbiota composition can contribute to the development of these diseases and be useful in their management. In this context, the consumption of fermented foods with probiotic properties, such as kefir, stands out due to its gut microbiota-modulating capacity. There is an increasing interest in the commercial use of kefir since it can be marketed as a natural beverage containing health-promoting bacteria and has been gaining international popularity in Latin America. Also the consumption of these drinks in Latin America seems to be even more relevant, given the socioeconomic situation of this population, which highlights the need for disease prevention at the expense of its treatment. In this narrative review, we discuss how kefir may work against obesity, diabetes mellitus, liver disease, cardiovascular disorders, immunity, and neurological disorders. Peptides, bioactive compounds and strains occurring in kefir, can modulate gut microbiota composition, low-grade inflammation and intestinal permeability, which consequently may generate health benefits. Kefir can also impact on the regulation of organism homeostasis, with a direct effect on the gut-brain axis, being a possible strategy for the prevention of metabolic diseases. Further studies are needed to standardize these bioactive compounds and better elucidate the mechanisms linking kefir and intestinal microbiota modulation. However, due to the benefits reported, low cost and ease of preparation, kefir seems to be a promising approach to prevent and manage microbiota-related diseases in Latin America and the rest of the world.
Analysis of miRNA-mRNA Crosstalk in Radiation-Induced Mouse Thymic Lymphomas to Identify miR-486 as a Critical Regulator by Targeting IGF2BP3 mRNA
Authors: Zhao Hainan , Dong Suhe , Du Jicong , Xia Penglin , Liu Ruling , Liu Tingting , Yang Yajie , Cheng Ying , Cai Jianming , Liu Cong , Gao Fu , Liu Hu
Published: February 2021

Ionizing radiation is one of the common environmental carcinogens. miRNAs play critical roles in the processes of tumor occurrence, development, metastasis. However, the relationship between radiation-induced carcinogenesis and miRNA rarely reported. This study is aimed to investigate the effect of miRNAs on radiation-induced carcinogenesis. In this study we established the radiation-induced thymic lymphoma mice model. By using miRNA array of RTL tissue and predicting for miRNAs target genes, a miRNA-mRNA crosstalk network was established. Based on this network, we identified a critical miRNA, miR-486, which was the most down-regulated in the radiation-induced carcinogenesis. Then the function of miR-486 was confirmed by using knockout mice and cellular experiments. As a result, miR-486 could inhibit proliferation of mouse lymphoma cells by targeting IGF2BP3 mRNA. The adenovirus over-expression miR-486 vector reduced tumorigenesis in vivo. MiR-486 knockout mice have a strong tendency of radiation-induced carcinogenesis. In conclusion, miR-486 inhibits the proliferation of lymphoma cells and tumorigenesis induced by radiation through targeting IGF2BP3.
Efficacy of BRAF Inhibitors in Combination With Stereotactic Radiosurgery for the Treatment of Melanoma Brain Metastases: A Systematic Review and Meta-Analysis
Authors: Khan Muhammad , Zheng Tao , Zhao Zhihong , Arooj Sumbal , Liao Guixiang
Published: February 2021

Background

BRAF inhibitors have improved the outcome for patients with BRAF mutant metastatic melanoma and have shown intracranial responses in melanoma brain metastases. Stereotactic radiosurgery (SRS) is being used as a local treatment for melanoma brain metastasis (MBM) with better local control and survival. We searched for studies comparing the combination of two treatments with SRS alone to detect any clinical evidence of synergism.

Materials and Methods

PubMed, EMBASE, Medline, and Cochrane library were searched until May 2020 for studies with desired comparative outcomes. Outcomes of interest that were obtained for meta-analysis included survival as the primary, and local control as the secondary outcome.

Results

A total of eight studies involving 976 patients with MBM were selected. Survival was significantly improved for patients receiving BRAF inhibitor plus SRS in comparison to SRS alone as assessed from the time of SRS induction (SRS survival: hazard ratio [HR] 0.67 [0.58–0.79], p <0.00001), from the time of brain metastasis diagnosis (BM survival: HR 0.65 [0.54, 0.78], p < 0.00001), or from the time of primary diagnosis (PD survival: HR 0.74 [0.57–0.95], p = 0.02). Dual therapy was also associated with improved local control, indicating an additive effect of the two treatments (HR 0.53 [0.31–0.93], p=0.03). Intracranial hemorrhage was higher in patients receiving BRAF inhibitors plus SRS than in those receiving SRS alone (OR, 3.16 [1.43–6.96], p = 0.004).

Conclusions

BRAF inhibitors in conjunction with SRS as local treatment appear to be efficacious. Local brain control and survival improved in patients with MBM receiving dual therapy. Safety assessment would need to be elucidated further as the incidence of intracranial hemorrhage was increased.
Mitochondria’s Role in the Maintenance of Cancer Stem Cells in Glioblastoma
Authors: Iranmanesh Yasaman , Jiang Biao , Favour Okoye C. , Dou Zhangqi , Wu Jiawei , Li Jinfan , Sun Chongran
Published: February 2021

Glioblastoma (GBM), one of the deadliest primary brain malignancies, is characterized by a high recurrence rate due to its limited response to existing therapeutic strategies such as chemotherapy, radiation therapy, and surgery. Several mechanisms and pathways have been identified to be responsible for GBM therapeutic resistance. Glioblastoma stem cells (GSCs) are known culprits of GBM resistance to therapy. GSCs are characterized by their unique self-renewal, differentiating capacity, and proliferative potential. They form a heterogeneous population of cancer stem cells within the tumor and are further divided into different subpopulations. Their distinct molecular, genetic, dynamic, and metabolic features distinguish them from neural stem cells (NSCs) and differentiated GBM cells. Novel therapeutic strategies targeting GSCs could effectively reduce the tumor-initiating potential, hence, a thorough understanding of mechanisms involved in maintaining GSCs’ stemness cannot be overemphasized. The mitochondrion, a regulator of cellular physiological processes such as autophagy, cellular respiration, reactive oxygen species (ROS) generation, apoptosis, DNA repair, and cell cycle control, has been implicated in various malignancies (for instance, breast, lung, and prostate cancer). Besides, the role of mitochondria in GBM has been extensively studied. For example, when stressors, such as irradiation and hypoxia are present, GSCs utilize specific cytoprotective mechanisms like the activation of mitochondrial stress pathways to survive the harsh environment. Proliferating GBM cells exhibit increased cytoplasmic glycolysis in comparison to terminally differentiated GBM cells and quiescent GSCs that rely more on oxidative phosphorylation (OXPHOS). Furthermore, the Warburg effect, which is characterized by increased tumor cell glycolysis and decreased mitochondrial metabolism in the presence of oxygen, has been observed in GBM. Herein, we highlight the importance of mitochondria in the maintenance of GSCs.
YTH Domain Proteins: A Family of m6A Readers in Cancer Progression
Authors: Xu Yirong , Zhang Wei , Shen Feng , Yang Xi , Liu Huilan , Dai Shengbin , Sun Xinchen , Huang Junxing , Guo Qing
Published: February 2021

N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNAs (mRNAs). m6A RNA methylation is involved in all stages of RNA life cycle, from RNA processing, nuclear output, translation regulation to RNA degradation, indicating that m6A has various functions affecting RNA metabolism positively or negatively. Reading proteins are vital in regulating the translation and stability of m6A mRNAs positively or negatively. Recent studies have enhanced the understanding of the molecular mechanism of the YT521-B homology (YTH) domain family and the modification of m6A. This study aimed to review the specific mechanisms, functions, and interactions of the YTH domain protein family. It also discussed future research directions, thus providing new ideas for the clinical diagnosis and targeted therapy of cancer.
A Novel Treatment Concept for Advanced Stage Mandibular Osteoradionecrosis Combining Isodose Curve Visualization and Nerve Preservation: A Prospective Pilot Study
Authors: van Baar Gustaaf J. C. , Leeuwrik Lars , Lodders Johannes N. , Liberton Niels P. T. J. , Karagozoglu K. Hakki , Forouzanfar Tymour , Leusink Frank K. J.
Published: February 2021

Background

Osteoradionecrosis (ORN) of the mandible is a severe complication of radiation therapy in head and neck cancer patients. Treatment of advanced stage mandibular osteoradionecrosis may consist of segmental resection and osseous reconstruction, often sacrificing the inferior alveolar nerve (IAN). New computer-assisted surgery (CAS) techniques can be used for guided IAN preservation and 3D radiotherapy isodose curve visualization for patient specific mandibular resection margins. This study introduces a novel treatment concept combining these CAS techniques for treatment of advanced stage ORN.

Methods

Our advanced stage ORN treatment concept includes consecutively: 1) determination of the mandibular resection margins using a 3D 50 Gy isodose curve visualization, 2) segmental mandibular resection with preservation of the IAN with a two-step cutting guide, and 3) 3D planned mandibular reconstruction using a hand-bent patient specific reconstruction plate. Postoperative accuracy of the mandibular reconstruction was evaluated using a guideline. Objective and subjective IAN sensory function was tested for a period of 12 months postoperatively.

Results

Five patients with advanced stage ORN were treated with our ORN treatment concept using the fibula free flap. A total of seven IANs were salvaged in two men and three women. No complications occurred and all reconstructions healed properly. Neither non-union nor recurrence of ORN was observed. Sensory function of all IANs recovered after resection up to 100 percent, including the patients with a pathologic fracture due to ORN. The accuracy evaluation showed angle deviations limited to 3.78 degrees. Two deviations of 6.42° and 7.47° were found. After an average of 11,6 months all patients received dental implants to complete oral rehabilitation.

Conclusions

Our novel ORN treatment concept shows promising results for implementation of 3D radiotherapy isodose curve visualization and IAN preservation. Sensory function of all IANs recovered after segmental mandibular resection.
Development of a Gene-Based Prediction Model for Recurrence of Colorectal Cancer Using an Ensemble Learning Algorithm
Authors: Chan Han-Ching , Chattopadhyay Amrita , Chuang Eric Y. , Lu Tzu-Pin
Published: February 2021

It is difficult to determine which patients with stage I and II colorectal cancer are at high risk of recurrence, qualifying them to undergo adjuvant chemotherapy. In this study, we aimed to determine a gene signature using gene expression data that could successfully identify high risk of recurrence among stage I and II colorectal cancer patients. First, a synthetic minority oversampling technique was used to address the problem of imbalanced data due to rare recurrence events. We then applied a sequential workflow of three methods (significance analysis of microarrays, logistic regression, and recursive feature elimination) to identify genes differentially expressed between patients with and without recurrence. To stabilize the prediction algorithm, we repeated the above processes on 10 subsets by bagging the training data set and then used support vector machine methods to construct the prediction models. The final predictions were determined by majority voting. The 10 models, using 51 differentially expressed genes, successfully predicted a high risk of recurrence within 3 years in the training data set, with a sensitivity of 91.18%. For the validation data sets, the sensitivity of the prediction with samples from two other countries was 80.00% and 91.67%. These prediction models can potentially function as a tool to decide if adjuvant chemotherapy should be administered after surgery for patients with stage I and II colorectal cancer.
Case Report: RAB10-ALK: A Novel ALK Fusion in a Patient With Gastric Cancer
Authors: Wen Zhengqi , Xiong Dun , Zhang Shurong , Liu Jiankun , Li Bitao , Li Raomei , Zhang Hushan
Published: February 2021

Gastric cancer is one of the most common cancers, while the current treatment options for gastric cancer are relatively scarce due to insufficient understanding of molecular characteristics and subtypes of gastric cancer. Different gene rearrangements of anaplastic lymphocyte kinase (ALK) have been reported in several types of cancer, especially in NSCLC. The first-generation ALK tyrosine kinase inhibitor (TKI) crizotinib, second-generation (ceritinib, alectinib, and brigatinib) and third-generation (lorlatinib) ALK-TKIs have been widely used for NSCLC patients with ALK rearrangement. However, little was reported about ALK mutation in gastric cancer (GC). Here we identified a novel form of ALK fusion, a case of GC with RAB10-ALK fusion, and this is the first report of ALK fusion in gastric cancer.
SARS-CoV-2 and the Gastrointestinal Tract in Children
Authors: Puoti Maria Giovanna , Rybak Anna , Kiparissi Fevronia , Gaynor Edward , Borrelli Osvaldo
Published: February 2021

Coronavirus disease 2019 (COVID-19), caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is predominantly a respiratory disease. However, its significant impact on the gastrointestinal (GI) system is now well-known. SARS-CoV-2 enters cells via the angiotensin-converting enzyme-2 (ACE-2) receptor, which is abundantly expressed on lung cells, but also on enterocytes. Several etiopathogenetic mechanisms have been postulated to explain the GI involvement in COVID-19, including loss in intestinal absorption, microscopic mucosal inflammation and impaired ACE-2 function, which plays a significant role in maintaining gut homeostasis. In children the GI manifestations include anorexia, nausea, vomiting, diarrhea and abdominal pain, which may represent the earliest presenting symptoms of the disease. However, although rare, a significant GI mucosal inflammation, such as terminal ileitis mimicking an atypical appendicitis, and other GI manifestations have been reported. COVID-19 pandemic has posed a significant challenge in healthcare provision in term of ability in providing safe diagnostic procedures, face-to-face consultations, and offering comprehensive care. For instance, changes in health services have raised the risk of empirical or sub-optimal management of chronic GI disorders such as inflammatory bowel disease (IBD) due to delayed endoscopic and clinical assessment. This review will discuss the acute GI involvement in COVID-19 in children and reflect on challenges and major changes observed in clinical practice during COVID-19 pandemic by sharing both the published literature and personal experience. We also suggest potential strategies for providing optimal gastroenterology care during this unprecedented era.
Expression of Low Affinity Nerve Growth Factor Receptor p75 in Classic Bladder Exstrophy
Authors: Promm Martin , Otto Wolfgang , Weber Florian , Götz Stefanie , Burger Maximilian , Müller Karolina , Rubenwolf Peter , Neuhuber Winfried , Roesch Wolfgang H.
Published: February 2021

Successful primary closure of classic bladder exstrophy (BE) is crucial for development of bladder capacity and voided continence. It is universally agreed that an intensive pain management including the use of caudal epidural anesthesia is an essential cornerstone for the outcome of this complex surgery. Whether and to what extent pain is caused by structural or functional changes is not yet known. The nerve growth factor (NGF) is regarded as a marker for pain in different bladder disorders. This prospective study investigated the role of histological alterations and NGF in patients with BE including 34 patients with BE and 6 patients with congenital vesicoureterorenal reflux (VUR) who served as controls. Between January 2015 and April 2020 transmural bladder biopsies were taken from the posterior bladder wall during delayed primary bladder closure. The samples were stained for histological evaluation and subjected to immunohistochemistry to analyze NGFR p75. Differences in histological alterations were examined with Fisher's exact test, and Mann-Whitney-U-test was used to compare the NGFR p75 staining intensity between patients with BE and controls. Patients with BE showed significantly more often acute inflammation (p < 0.001), squamous metaplasia (p = 0.002), and cystitis glandularis (p = 0.005) as well as NGFR p75 in the urothelium (p = 0.003) than patients with VUR. A limitation of this study is the small number of participants due to the rare disease entity. Similar to other painful bladder disorders, pain transmission in BE after intitial closure may in part be facilitated by elevated NGF signaling through its receptor.
Expanded Neonatal Bloodspot Screening Programmes: An Evaluation Framework to Discuss New Conditions With Stakeholders
Authors: Jansen Marleen E. , Klein Anne W. , Buitenhuis Erika C. , Rodenburg Wendy , Cornel Martina C.
Published: February 2021

Neonatal bloodspot screening (NBS) programmes that screen for rare but serious conditions are expanding worldwide. Fast developments for testing and treatment put pressure on implementation processes. In 2015 the Netherlands embarked on an NBS expansion from 17 to 31 conditions. An evaluation framework was developed based on international NBS frameworks to gain insight in test properties, clinical findings, follow-up and implementation. A stakeholder process took place with implications for the planning of the expanded NBS panel. The evaluation framework progressed into a go/no go framework to start national screening, and is currently explored as basis for continuous evaluation of the NBS panel. The framework and stakeholder process may serve as an example for other programmes.
Drug Repurposing and Polypharmacology to Fight SARS-CoV-2 Through Inhibition of the Main Protease
Authors: Pinzi Luca , Tinivella Annachiara , Caporuscio Fabiana , Rastelli Giulio
Published: February 2021

The outbreak of a new coronavirus (SARS-CoV-2), which is responsible for the COVID-19 disease and is spreading rapidly around the world, urgently requires effective therapeutic treatments. In this context, drug repurposing represents a valuable strategy, as it enables accelerating the identification of drug candidates with already known safety profiles, possibly aiding in the late stages of clinical evaluation. Moreover, therapeutic treatments based on drugs with beneficial multi-target activities (polypharmacology) may show an increased antiviral activity or help to counteract severe complications concurrently affecting COVID-19 patients. In this study, we present the results of a computational drug repurposing campaign that aimed at identifying potential inhibitors of the main protease (Mpro) of the SARS-CoV-2. The performedin silicoscreening allowed the identification of 22 candidates with putative SARS-CoV-2 Mproinhibitory activity. Interestingly, some of the identified compounds have recently entered clinical trials for COVID-19 treatment, albeit not being assayed for their SARS-CoV-2 antiviral activity. Some candidates present a polypharmacology profile that may be beneficial for COVID-19 treatment and, to the best of our knowledge, have never been considered in clinical trials. For each repurposed compound, its therapeutic relevance and potential beneficial polypharmacological effects that may arise due to its original therapeutic indication are thoroughly discussed.
Instability of Double-Periodic Waves in the Nonlinear Schrödinger Equation
Authors: Pelinovsky Dmitry E.
Published: February 2021

It is shown how to compute the instability rates for the double-periodic solutions to the cubic NLS (nonlinear Schrödinger) equation by using the Lax linear equations. The wave function modulus of the double-periodic solutions is periodic both in space and time coordinates; such solutions generalize the standing waves which have the time-independent and space-periodic wave function modulus. Similar to other waves in the NLS equation, the double-periodic solutions are spectrally unstable and this instability is related to the bands of the Lax spectrum outside the imaginary axis. A simple numerical method is used to compute the unstable spectrum and to compare the instability rates of the double-periodic solutions with those of the standing periodic waves.
Controversial Roles of the Renin Angiotensin System and Its Modulators During the COVID-19 Pandemic
Authors: Gressens Simon B. , Leftheriotis Georges , Dussaule Jean-Claude , Flamant Martin , Levy Bernard I. , Vidal-Petiot Emmanuelle
Published: February 2021

Since December 2019, the coronavirus 2019 (COVID-19) pandemic has rapidly spread and overwhelmed healthcare systems worldwide, urging physicians to understand how to manage this novel infection. Early in the pandemic, more severe forms of COVID-19 have been observed in patients with cardiovascular comorbidities, who are often treated with renin-angiotensin aldosterone system (RAAS)-blockers, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), but whether these are indeed independent risk factors is unknown. The cellular receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the membrane-bound angiotensin converting enzyme 2 (ACE2), as for SARS-CoV(-1). Experimental data suggest that expression of ACE2 may be increased by RAAS-blockers, raising concerns that these drugs may facilitate viral cell entry. On the other hand, ACE2 is a key counter-regulator of the RAAS, by degrading angiotensin II into angiotensin (1-7), and may thereby mediate beneficial effects in COVID-19. These considerations have raised concerns about the management of these drugs, and early comments shed vivid controversy among physicians. This review will describe the homeostatic balance between ACE-angiotensin II and ACE2-angiotensin (1-7) and summarize the pathophysiological rationale underlying the debated role of the RAAS and its modulators in the context of the pandemic. In addition, we will review available evidence investigating the impact of RAAS blockers on the course and prognosis of COVID-19 and discuss why retrospective observational studies should be interpreted with caution. These considerations highlight the importance of solid evidence-based data in order to guide physicians in the management of RAAS-interfering drugs in the general population as well as in patients with more or less severe forms of SARS-CoV-2 infection.
DAM: Hierarchical Adaptive Feature Selection Using Convolution Encoder Decoder Network for Strawberry Segmentation
Authors: Ilyas Talha , Umraiz Muhammad , Khan Abbas , Kim Hyongsuk
Published: February 2021

Autonomous harvesters can be used for the timely cultivation of high-value crops such as strawberries, where the robots have the capability to identify ripe and unripe crops. However, the real-time segmentation of strawberries in an unbridled farming environment is a challenging task due to fruit occlusion by multiple trusses, stems, and leaves. In this work, we propose a possible solution by constructing a dynamic feature selection mechanism for convolutional neural networks (CNN). The proposed building block namely a dense attention module (DAM) controls the flow of information between the convolutional encoder and decoder. DAM enables hierarchical adaptive feature fusion by exploiting both inter-channel and intra-channel relationships and can be easily integrated into any existing CNN to obtain category-specific feature maps. We validate our attention module through extensive ablation experiments. In addition, a dataset is collected from different strawberry farms and divided into four classes corresponding to different maturity levels of fruits and one is devoted to background. Quantitative analysis of the proposed method showed a 4.1% and 2.32% increase in mean intersection over union, over existing state-of-the-art semantic segmentation models and other attention modules respectively, while simultaneously retaining a processing speed of 53 frames per second.
Isolation and Functional Analysis of Genes Involved in Polyacylated Anthocyanin Biosynthesis in Blue Senecio cruentus
Authors: Lu Chenfei , Li Yajun , Cui Yumeng , Ren Jiangshan , Qi Fangting , Qu Jiaping , Huang He , Dai Silan
Published: February 2021

Polyacylated anthocyanins with multiple glycosyl and aromatic acyl groups tend to make flowers display bright and stable blue colours. However, there are few studies on the isolation and functional characterization of genes involved in the polyacylated anthocyanin biosynthesis mechanism, which limits the molecular breeding of truly blue flowers. Senecio cruentus is an important potted ornamental plant, and its blue flowers contain 3′,7-polyacylated delphinidin-type anthocyanins that are not reported in any other plants, suggesting that it harbours abundant gene resources for the molecular breeding of blue flowers. In this study, using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis of blue, carmine and white colours of cineraria cultivars “Venezia” (named VeB, VeC, and VeW, respectively), we found that 3′,7-polyacylated anthocyanin, cinerarin, was the main pigment component that determined the blue colour of ray florets of cineraria. Based on the transcriptome sequencing and differential gene expression (DEG) analysis combined with RT- and qRT-PCR, we found two genes encoding uridine diphosphate glycosyltransferase, named ScUGT1 and ScUGT4; two genes encoding acyl-glucoside-dependent glucosyltransferases which belong to glycoside hydrolase family 1 (GH1), named ScAGGT11 and ScAGGT12; one gene encoding serine carboxypeptidase-like acyltransferase ScSCPL2; and two MYB transcriptional factor genes ScMYB2 and ScMYB4, that were specifically highly expressed in the ray florets of VeB, which indicated that these genes may be involved in cinerarin biosynthesis. The function of ScSCPL2 was analysed by virus-induced gene silencing (VIGS) in cineraria leaves combined with HPLC-MS/MS. ScSCPL2 mainly participated in the 3′ and 7-position acylation of cinerarin. These results will provide new insight into the molecular basis of the polyacylated anthocyanin biosynthesis mechanism in higher plants and are of great significance for blue flower molecular breeding of ornamental plants.
Stress Makes the Difference: Social Stress and Social Anxiety in Decision-Making Under Uncertainty
Authors: Hengen Kristina M. , Alpers Georg W.
Published: February 2021

Stress and anxiety can both influence risk-taking in decision-making. While stress typically increases risk-taking, anxiety often leads to risk-averse choices. Few studies have examined both stress and anxiety in a single paradigm to assess risk-averse choices. We therefore set out to examine emotional decision-making under stress in socially anxious participants. In our study, individuals (N= 87) high or low in social anxiety completed an expanded variation of theBalloon Analogue Risk Task(BART). While inflating a balloon to a larger degree is rewarded, a possible explosion leads to (a) a loss of money and (b) it is followed by an emotional picture (i.e., a calm vs. an angry face). To induce stress before this task, participants were told that they would have to deliver a speech. We operationalized risk-taking by the number of pumps during inflation and its functionality by the amount of monetary gain. In addition, response times were recorded as an index of decisional conflict. Without the stressor, high socially anxious compared to low socially anxious participants did not differ in any of the dependent variables. However, under stress, the low socially anxious group took more risk and earned more money, while high socially anxious individuals remained more cautious and did not change their risk-taking under social stress. Overall, high socially anxious individuals made their decisions more hesitantly compared to low socially anxious individuals. Unexpectedly, there were no main effects or interactions with the valence of the emotional faces. This data shows that stress affects socially anxious individuals differently: in low socially anxious individuals stress fosters risk-taking, whereas high socially anxious individuals did not alter their behavior and remained risk-averse. The noveleBARTis a promising research tool to examine the specific factors that influence decision-making.
Evidence for Teaching in an Australian Songbird
Authors: Taylor Hollis
Published: February 2021

Song in oscine birds (as in human speech and song) relies upon the rare capacity of vocal learning. Transmission can be vertical, horizontal, or oblique. As a rule, memorization and production by a naïve bird are not simultaneous: the long-term storage of song phrases precedes their first vocal rehearsal by months. While a wealth of detail regarding songbird enculturation has been uncovered by focusing on the apprentice, whether observational learning can fully account for the ontogeny of birdsong, or whether there could also be an element of active teaching involved, has remained an open question. Given the paucity of knowledge on animal cultures, I argue for the utility of an inclusive definition of teaching that encourages data be collected across a wide range of taxa. Borrowing insights from musicology, I introduce the Australian pied butcherbird (Cracticus nigrogularis) into the debate surrounding mechanisms of cultural transmission. I probe the relevance and utility of mentalistic, culture-based, and functionalist approaches to teaching in this species. Sonographic analysis of birdsong recordings and observational data (including photographs) of pied butcherbird behavior at one field site provide evidence that I assess based on criteria laid down by Caro and Hauser, along with later refinements to their functionalist definition. The candidate case of teaching reviewed here adds to a limited but growing body of reports supporting the notion that teaching may be more widespread than is currently realized. Nonetheless, I describe the challenges of confirming that learning has occurred in songbird pupils, given the delay between vocal instruction and production, as well as the low status accorded to anecdote and other observational evidence commonly mustered in instances of purported teaching. As a corrective, I press for an emphasis on biodiversity that will guide the study of teaching beyond human accounts and intractable discipline-specific burdens of proof.
Evaluating Human-Computer Co-creative Processes in Music: A Case Study on the CHAMELEON Melodic Harmonizer
Authors: Zacharakis Asterios , Kaliakatsos-Papakostas Maximos , Kalaitzidou Stamatia , Cambouropoulos Emilios
Published: February 2021

CHAMELEON is a computational melodic harmonization assistant. It can harmonize a given melody according to a number of independent harmonic idioms or blends between idioms based on principles of conceptual blending theory. Thus, the system is capable of offering a wealth of possible solutions and viewpoints for melodic harmonization. This study investigates how human creativity may be influenced by the use of CHAMELEON in a melodic harmonization task. Professional and novice music composers participated in an experiment where they were asked to harmonize two similar melodies under two different conditions: one with and one without computational support. A control group harmonized both melodies without computational assistance. The influence of the system was examined both behaviorally, by comparing metrics of user-experience, and in terms of the properties of the artifacts (i.e., pitch class distribution and number of chord types characterizing each harmonization) that were created between the two experimental conditions. Results suggest that appreciation of the system was expertise-dependent (i.e., novices appreciated the computational support more than professionals). At the same time, users seemed to adopt more explorative strategies as a result of interaction with CHAMELEON based on the fact that the harmonizations created this way were more complex, diverse, and unexpected in comparison to the ones of the control group.
The Effects of Adult Ageing and Culture on the Tower of London Task
Authors: Phillips Louise H. , Lawrie Louisa , Schaefer Alexandre , Tan Cher Yi , Yong Min Hooi
Published: February 2021

Planning ability is important in everyday functioning, and a key measure to assess the preparation and execution of plans is the Tower of London (ToL) task. Previous studies indicate that older adults are often less accurate than the young on the ToL and that there may be cultural differences in performance on the task. However, potential interactions between age and culture have not previously been explored. In the current study we examined the effects of age on ToL performance in an Asian culture (Malaysia) and a Western culture (British) (n = 191). We also explored whether working memory, age, education, and socioeconomic status explained variance in ToL performance across these two cultures. Results indicated that age effects on ToL performance were greater in the Malaysian sample. Subsequent moderated mediation analysis revealed differences between the two cultures (British vs Malaysians), in that the age-related variance in ToL accuracy was accounted for by WM capacity at low and medium education levels only in the Malaysian sample. Demographic variables could not explain additional variance in ToL speed or accuracy. These results may reflect cultural differences in the familiarity and cognitive load of carrying out complex planning tasks.