bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergic Neuroprotection Between Ligusticum Chuanxiong Hort and Borneol Against Ischemic Stroke by Neurogenesis via Modulating Reactive Astrogliosis and Maintaining the Blood–Brain Barrier
Authors: Yu Bin , Yao Yao , Zhang Xiaofeng , Ruan Ming , Zhang Zhennian , Xu Li , Liang Tao , Lu Jinfu
Published: June 2021

Background:Ligusticum chuanxiong Hort (LCH) is a famous ethnomedicine in Asia known for its excellent output on stroke treatment, and borneol usually acts as an assistant for its reducing permeability of the blood–brain barrier (BBB) after stroke. Although their synergy against brain ischemia was verified in previous studies, the potential mechanism is still unknown.

Methods: The research aimed to explore the exact synergic mechanisms between LCH and borneol on neurogenesis within the areas of the dentate gyrus and subventricular zone. After treating middle cerebral artery occlusion rats with LCH (0.1 g/kg) and/or borneol (0.08 g/kg), the neurological severity score, brain infarct ratio, Nissl staining, Evans blue permeability, BBB ultrastructure, and expressions of von Willebrand factor and tight junction–associated proteins were measured. Co-localizations of Nestin+/BrdU+ and doublecortin+/BrdU+, and expressions of neuronal nuclei (NeuN) and glial fibrillary acidic protein (GFAP) were observed under a fluorescence microscope. Moreover, astrocyte polarization markers of complement component 3 and pentraxin 3, and relevant neurotrophins were also detected by immunoblotting.

Results: Basically, LCH and borneol had different focuses, although both of them decreased infarct areas, and increased quantity of Nissl bodies and expression of brain-derived neurotrophic factor. LCH increased the neurological severity score, NeuN+ cells, and the ratios of Nestin+/BrdU+ and doublecortin+/BrdU+, and decreased GFAP+ cells and ciliary neurotrophic factor expression. Additionally, it regulated the expressions of complement component 3 and pentraxin 3 to transform astrocyte phenotypes. Borneol improved BBB ultrastructure and increased the expressions of von Willebrand factor, tight junction–associated proteins, vascular endothelial growth factor, and vascular endothelial growth factor receptor 2. Unexpectedly, their combined therapy showed more obvious regulations on the Nissl score, Evans blue permeability, doublecortin+/BrdU+, NeuN+ cells, brain-derived neurotrophic factor, and vascular endothelial growth factor than both of their monotherapies.

Conclusions: The results indicated that LCH and borneol were complementary to each other in attenuating brain ischemia by and large. LCH mainly promoted neural stem cell proliferation, neurogenesis, and mature neuron preservation, which was probably related to the transformation of reactive astrocytes from A1 subtype to A2, while borneol preferred to maintain the integrity of the BBB, which provided neurogenesis with a homeostatic environment.
ABCB1 and ABCG2 Together Limit the Distribution of ABCB1/ABCG2 Substrates to the Human Retina and the ABCG2 Single Nucleotide Polymorphism Q141K (c.421C> A) May Lead to Increased Drug Exposure
Authors: El Biali Myriam , Karch Rudolf , Philippe Cécile , Haslacher Helmuth , Tournier Nicolas , Hacker Marcus , Zeitlinger Markus , Schmidl Doreen , Langer Oliver , Bauer Martin
Published: June 2021

The widely expressed and poly-specific ABC transporters breast cancer resistance protein (ABCG2) and P-glycoprotein (ABCB1) are co-localized at the blood-brain barrier (BBB) and have shown to limit the brain distribution of several clinically used ABCB1/ABCG2 substrate drugs. It is currently not known to which extent these transporters, which are also expressed at the blood-retinal barrier (BRB), may limit drug distribution to the human eye and whether the ABCG2 reduced-function single-nucleotide polymorphism (SNP) Q141K (c.421C > A) has an impact on retinal drug distribution. Ten healthy male volunteers (five subjects with the c.421CC and c.421CA genotype, respectively) underwent two consecutive positron emission tomography (PET) scans after intravenous injection of the model ABCB1/ABCG2 substrate [11C]tariquidar. The second PET scan was performed with concurrent intravenous infusion of unlabelled tariquidar to inhibit ABCB1 in order to specifically reveal ABCG2 function.In response to ABCB1 inhibition with unlabelled tariquidar, ABCG2 c.421C > A genotype carriers showed significant increases (as compared to the baseline scan) in retinal radiotracer influx K1 (+62 ± 57%, p = 0.043) and volume of distribution VT (+86 ± 131%, p = 0.043), but no significant changes were observed in subjects with the c.421C > C genotype. Our results provide the first evidence that ABCB1 and ABCG2 may together limit the distribution of systemically administered ABCB1/ABCG2 substrate drugs to the human retina. Functional redundancy between ABCB1 and ABCG2 appears to be compromised in carriers of the c.421C > A SNP who may therefore be more susceptible to transporter-mediated drug-drug interactions at the BRB than non-carriers.
Translation Initiation Factor eIF4E Positively Modulates Conidiogenesis, Appressorium Formation, Host Invasion and Stress Homeostasis in the Filamentous Fungi Magnaporthe oryzae
Authors: Batool Wajjiha , Shabbir Ammarah , Lin Lili , Chen Xiaomin , An Qiuli , He Xiongjie , Pan Shu , Chen Shuzun , Chen Qinghe , Wang Zonghua , Norvienyeku Justice
Published: June 2021

Translation initiation factor eIF4E generally mediates the recognition of the 5’cap structure of mRNA during the recruitment of the ribosomes to capped mRNA. Although the eIF4E has been shown to regulate stress response in Schizosaccharomyces pombe positively, there is no direct experimental evidence for the contributions of eIF4E to both physiological and pathogenic development of filamentous fungi. We generated Magnaporthe oryzae eIF4E (MoeIF4E3) gene deletion strains using homologous recombination strategies. Phenotypic and biochemical analyses of MoeIF4E3 defective strains showed that the deletion of MoeIF4E3 triggered a significant reduction in growth and conidiogenesis. We also showed that disruption of MoeIF4E3 partially impaired conidia germination, appressorium integrity and attenuated the pathogenicity of ΔMoeif4e3 strains. In summary, this study provides experimental insights into the contributions of the eIF4E3 to the development of filamentous fungi. Additionally, these observations underscored the need for a comprehensive evaluation of the translational regulatory machinery in phytopathogenic fungi during pathogen-host interaction progression.
Digital Phenotyping to Delineate Salinity Response in Safflower Genotypes
Authors: Thoday-Kennedy Emily , Joshi Sameer , Daetwyler Hans D. , Hayden Matthew , Hudson David , Spangenberg German , Kant Surya
Published: June 2021

Salinity is a major contributing factor to the degradation of arable land, and reductions in crop growth and yield. To overcome these limitations, the breeding of crop varieties with improved salt tolerance is needed. This requires effective and high-throughput phenotyping to optimize germplasm enhancement. Safflower (Carthamus tinctorius L.), is an underappreciated but highly versatile oilseed crop, capable of growing in saline and arid environments. To develop an effective and rapid phenotyping protocol to differentiate salt responses in safflower genotypes, experiments were conducted in the automated imaging facility at Plant Phenomics Victoria, Horsham, focussing on digital phenotyping at early vegetative growth. The initial experiment, at 0, 125, 250, and 350 mM sodium chloride (NaCl), showed that 250 mM NaCl was optimum to differentiate salt sensitive and tolerant genotypes. Phenotyping of a diverse set of 200 safflower genotypes using the developed protocol defined four classes of salt tolerance or sensitivity, based on biomass and ion accumulation. Salt tolerance in safflower was dependent on the exclusion of Na+ from shoot tissue and the maintenance of K+ uptake. Salinity response identified in glasshouse experiments showed some consistency with the performance of representatively selected genotypes tested under sodic field conditions. Overall, our results suggest that digital phenotyping can be an effective high-throughput approach in identifying candidate genotypes for salt tolerance in safflower.
Rail Transport Delay and Its Effects on the Perceived Importance of a Real-Time Information
Authors: Rezapour Mahdi , Ferraro F. Richard
Published: June 2021

Various psychological feelings that commuters might experience due to the shortcomings of a public transport are a major concern for transport policy makers. Those shortcomings would be translated into various negative psychological feelings, which would consequently tarnish the perceived quality of the public transport system in terms of its characteristics, e.g., the perceived quality of the passengers' information system (PIS). A delay has often been defined as the difference between the real arrival of a transport and the scheduled arrival of based on the PIS. The main question this study seeks to answer is how passengers view the PIS while undergoing various psychological negative impacts due to delay? This is especially important when the PIS is not precise. Previous studies on the importance of real-time information mainly focus on the impact of PIS on the satisfaction of commuters, or the reliability of the public transport. However, they rarely consider the negative psychological impacts that delays might have on commuters, and how those negative feelings might be aggravated by providing inaccurate information for the commuters. The proposed study is based on completed questionnaires by 396 passengers waiting for a rail transport in Malaysia; the rail transport was experiencing frequent long delays due to various mechanical malfunctions. In addition, the PIS provided for the passengers were mainly imprecise, and was updated regularly. The relationship between various considered variables, and a related latent factor, were formed by means of factor analysis. The results of internal consistency and validity highlight acceptable factors to be considered for a structural equation modeling (SEM) model. Three latent factors were found to impact the latent factor of PIS. For instance, it was found that the relationship between motion sickness factor and the response of PIS is not by a direct relationship between those two factors, but through the mediation of a latent physiological factor. On the other hand, the impact of the psychological feelings of the commuter by PIS is higher than its physiological effects. The results of this study have an important managerial implication for policy makers that even if the delay is inevitable, an accurate PIS could be provided to reduce the associated negative feelings of delay. Extensive discussion has been had about identification of a best fit model and process of model's parameters' estimation.
Heart and Head: Profiles and Predictors of Self-Assessed Cognitive and Affective Empathy in a Sample of Medical and Health Professional Students
Authors: Giusti Laura , Mammarella Silvia , Salza Anna , Ussorio Donatella , Bianco Denise , Casacchia Massimo , Roncone Rita
Published: June 2021

For medical and health professions, students learning to respond to others' distress with well-regulated empathy is an important developmental skill linked to positive health outcomes and professionalism. Our study aimed to investigate the sociodemographic, psychological, and psychosocial differences between medical (MS) and health professional (HPS) students and their empathic abilities, since both populations share common stressors, namely, dealing with suffering people. Additionally, we were interested in assessing the psychological and psychosocial predictors of empathy of MS compared to HPS. One hundred thirty MS and 86 HPS were administered the Patient Health Questionnaire-9, Interpersonal Reactivity Index, Integrative Hope Scale, and UCLA Loneliness Scale. The two groups showed differences in their contextual characteristics, with the HPS group having larger families, lower parents' education levels, and lower family income compared to the MS group. In both groups, ~15% of students reported previous contact for psychological problems. A higher proportion of HPS (23.3%) reported depressive symptoms than MS (10%), and female HPS reported more intense feelings of loneliness than other subgroups of students. No differences were found between the two groups in self-assessed cognitive and affective empathy. In both groups, women showed greater affective scores than men and, at the same time, seemed to be particularly prone to personal distress. The cognitive empathic dimension of “perspective taking” was predicted by young age (OR, 612; 95% CI, 1.395–15.242) and the overall socioeconomic status (OR, 3.175; 95% CI, 1.154–8.734) of the HPS. Self-assessed affective competence was predicted by female gender (OR, 3.112; 95% CI, 1.328–7.288), depressive symptomatology (OR, 2.777; 95% CI, 1.004–7.681), higher mother's level of education (OR, 2.764; 95% CI, 1.147–6.659), and feeling of hope related to social relationships (OR, 1.367; 95% CI, 1.152–1.622). Risk factors for poor self-assessed affective emphatic skills were previous contact for psychological problems (OR, 3.263; 95% CI, 1.238–8.601) and feelings of loneliness (OR, 1.18; 95% CI, 1.09–1.276). Our findings emphasize the need to test psychosocial models to better understand empathic skills.
Social Value and Urban Sustainability in Food Markets
Authors: Guzmán-Pérez Beatriz , Pérez-Monteverde María Victoria , Mendoza-Jiménez Javier , Román-Cervantes Cándido
Published: June 2021

Urban food markets can promote sustainable development through the generation of social value in the spaces where they are located and contribute to sustainability on a global scale. To measure this, indicators are required to evaluate and monitor these markets. Studies in this regard are scarce and often developed according to top-down schemes. This study seeks to remedy this relative deficiency and aims to design specific social sustainability metrics for these organizations from a bottom-up perspective. The Integrated Social Value model is used. This social accounting system is considered appropriate in this study due to the phenomenological approach on which it is based and is applied to a service cooperative located in the Canary Islands. The main contribution of this work is that new social sustainability indicators are obtained and applied to the analysis of an entity, and they are relevant and understandable to stakeholders. This would provide, in future developments, a system of sustainability indicators for similar organizations in Spain.
BDNF as a Biomarker of Cognition in Schizophrenia/Psychosis: An Updated Review
Authors: Nieto Rodrigo R. , Carrasco Andrea , Corral Sebastian , Castillo Rolando , Gaspar Pablo A. , Bustamante M. Leonor , Silva Hernan
Published: June 2021

Brain Derived Neurotrophic Factor (BDNF) has been linked to cognitive symptoms of schizophrenia, which has been documented in previous reviews by several authors. However, a trend has recently emerged in this field moving from studying schizophrenia as a disease to studying psychosis as a group. This review article focuses on recent BDNF studies in relation to cognition in human subjects during different stages of the psychotic process, including subjects at high risk of developing psychosis, patients at their first episode of psychosis, and patients with chronic schizophrenia. We aim to provide an update of BDNF as a biomarker of cognitive function on human subjects with schizophrenia or earlier stages of psychosis, covering new trends, controversies, current research gaps, and suggest potential future developments in the field. We found that most of current research regarding BDNF and cognitive symptoms in psychosis is done around schizophrenia as a disease. Therefore, it is necessary to expand the study of the relationship between BDNF and cognitive symptoms to psychotic illnesses of different stages and origins.
Attitudes and Acceptance of COVID-19 Vaccination Among Nurses and Midwives in Cyprus: A Cross-Sectional Survey
Authors: Fakonti Georgia , Kyprianidou Maria , Toumbis Giannos , Giannakou Konstantinos
Published: June 2021

Healthcare workers are at the frontline of the COVID-19 pandemic and have been identified as a priority target group for COVID-19 vaccines. This study aimed to determine the COVID-19 vaccination intention among nurses and midwives in Cyprus and reveal the influential factors that affected their decision. An Internet-based cross-sectional survey was conducted between December 8 and 28, 2020. Data collection was accomplished using a self-administered questionnaire with questions about socio-demographic characteristics, questions assessing general vaccination-related intentions and behaviors, and the intention to accept COVID-19 vaccination. A sample of 437 responders answered the survey, with 93% being nurses and 7% midwives. A small proportion of the participants would accept a vaccine against COVID-19, while 70% could be qualified as “vaccine hesitant.” The main reasons for not receiving the COVID-19 vaccine were concerns about the vaccine's expedited development and fear of side effects. More females, individuals with a larger median age, and a higher number of years of working experience, intended to accept the COVID-19 vaccination, compared with those not intended to accept and undecided groups (p< 0.01). Having a seasonal flu vaccination in the last 5 years, receiving the vaccines recommended for health professionals, and working in the private sector were associated with a higher probability of COVID-19 vaccination acceptance. A considerable rate of nurses and midwives in Cyprus reported unwillingness to receive a COVID-19 vaccine due to vaccine-related concerns. Our findings highlight the need for forthcoming vaccination campaigns and programs to tackle coronavirus vaccine hesitancy barriers to achieve the desirable vaccination coverage.
Risk Factors of Mortality From Pneumocystis Pneumonia in Non-HIV Patients: A Meta-Analysis
Authors: Wang Yuqiong , Zhou Xiaoyi , Saimi Maidinuer , Huang Xu , Sun Ting , Fan Guohui , Zhan Qingyuan
Published: June 2021

Background: We performed a meta-analysis to systematically review the risk factors of mortality from non-HIV-related Pneumocystis pneumonia (PcP) and provide the theoretical basis for managing non-HIV-related PcP.

Methods: PubMed, Embase, Web of Science, the Cochrane Library and CNKI databases were searched. A meta-analysis of the risk factors of mortality from non-HIV-related PcP was conducted.

Results: A total of 19 studies and 1,310 subjects were retrieved and included in the meta-analysis, including 485 and 825 patients in the non-survivor and survivor groups, respectively. In the primary analysis, age, concomitant with other pulmonary diseases at diagnosis of PcP, solid tumors, cytomegalovirus(CMV) co-infection, lactate dehydrogenase (LDH), lymphocyte count, invasive ventilation during hospitalization, and pneumothorax were associated with mortality from non-HIV-related PcP, whereas sex, albumin, PcP prophylaxis, use of corticosteroids after admission, and time from onset of symptoms to treatment were not associated with mortality from non-HIV-related PcP.

Conclusions: The mortality rate of non-HIV-infected patients with PcP was still high. Age, concomitant with other pulmonary diseases at diagnosis of PcP, solid tumors, CMV co-infection, LDH, lymphocyte count, invasive ventilation during hospitalization, and pneumothorax were risk factors of mortality from non-HIV-related PcP. Improved knowledge of prognostic factors is crucial to guide early treatment.
Can Methane-Eating Bacteria in Drylands Help Us Reduce Greenhouse Gases?
Authors: Lafuente Angela , Cano-Díaz Concha
Published: June 2021

What is a dryland? The first thing that may come to your mind is a desert-like place where nothing can live or grow. Despite the scarcity of water, dryland ecosystems are diverse and will expand due to global climate change. The main cause of global warming is the increase of greenhouse gases in our atmosphere. To solve this, we obviously need to reduce the emission of greenhouse gases, but the study of microorganisms in nature also gives us exciting clues for how to address the problem of global warming. Microorganisms live in all possible Earth environments, and luckily some of them can even take greenhouse gases from the air as their food! In this article, we describe our search of the global soils for bacteria that can consume one of the most powerful greenhouse gases, methane (CH4). Contrary to what was expected, we found that these bacteria live in drylands all over the world!
Application Analysis of Positive-Pressure Connector in Invasive Blood Pressure Monitoring in Coronary Interventional Therapy
Authors: Wang Aili , Liu Junying , Peng Wanzhong , Jiang Yang , Guo Lina , Xu Zesheng
Published: June 2021

Background: In order to reduce the risk of invasive blood pressure monitoring and improve the safety and efficiency, this article mainly analyzes the effectiveness and safety of using positive-pressure connector for invasive blood pressure monitoring in patients with coronary artery interventional therapy, so as to improve the invasive blood pressure monitoring method.

Aim: To study and analyze the application of positive-pressure connector in invasive blood pressure monitoring in coronary interventional therapy.

Methods: From October 2017 to October 2019, a total of 120 patients admitted to Cangzhou Central Hospital, Cangzhou, Hebei, China, for coronary interventional therapy with invasive blood pressure monitoring were selected and divided into a control group and an experimental group by drawing lots with 60 patients in each group. Positive-pressure connector was used for invasive blood pressure detection in the experimental group, and heparin cap connector was used for invasive blood pressure detection in the control group. The effectiveness and safety of blood pressure monitoring in the two groups were compared, and the influence of different joints on invasive blood pressure monitoring was analyzed.

Results: The influencing factors of puncture efficiency in the experimental group (6.67%) were significantly lower than those in the control group (30.00%) (P < 0.05). There was no significant difference in catheter bending between the experimental group and the control group (P > 0.05). The experimental group exhibited a remarkably higher puncture safety rate (93%) compared to the control group (67%) (P < 0.05). There was no significant difference in arterial blood pressure between the two groups with different indwelling time (P > 0.05). The frequency of extubation and reinsertion in the experimental group was significantly lower than that in the control group (P < 0.05). Factors influencing puncture safety in the experimental group were significantly lower than those in the control group (P < 0.05).

Conclusion: The use of positive-pressure connector for invasive blood pressure monitoring in patients with coronary artery interventional therapy can greatly improve the safety of blood pressure monitoring and reduce the suffering of patients. Therefore, the application of positive-pressure connector in invasive blood pressure monitoring is worthy of promotion and application in clinical practice.
Cochlear Meniere's: A Distinct Clinical Entity With Isolated Cochlear Hydrops on High-Resolution MRI?
Authors: Alonso Jose E. , Ishiyama Gail P. , Fujiwara Rance J. T. , Pham Nancy , Ledbetter Luke , Ishiyama Akira
Published: June 2021

Objective: Describe the clinical characteristics of patients with isolated cochlear endolymphatic hydrops (EH).

Study design: Clinical case series.

Setting: Tertiary Neurotology referral clinic.

Patients: All subjects presenting to a University Neurotology clinic during a 1-year period from July 2015 until August 2016 who had isolated cochlear EH on MRI. Patients with a history of temporal bone surgery prior to the MRI were excluded.

Intervention: High-resolution delayed-intravenous contrast MRI.

Main outcome measures: Audiometric and vestibular testing, clinical history analysis.

Results: 10 subjects demonstrated isolated, unilateral cochlear hydrops on MRI. None of these patients met the criteria for Meniere's disease. Mean age of the group was 66.4 years and most were males (70%). Unilateral aural fullness (70%), tinnitus (80%), and hearing loss (90%) were frequently observed. Only one patient presented with unsteadiness (10%) and one patient had a single isolated spell of positional vertigo 1 month prior to the MRI (10%) but no further vertigo spells in the 4 years following the MRI. The mean PTA was 37.8 dB which was significantly decreased from the non-affected ear with PTA of 17.9 (p < 0.001). One patient developed vertiginous spells and unsteadiness 4 years after initial presentation and a repeat MRI revealed progression to utricular, saccular and cochlear hydrops. Vestibular testing was obtained in five patients with one patient presenting with 50% caloric paresis and all others normal. The most common treatment tried was acetazolamide in seven patients with 86% reporting subjective clinical improvement. Two out of the 10 patients had a history of migraine (20%).

Conclusions: Patients with MRI exhibiting isolated cochlear EH present with predominantly auditory symptoms: mild to moderate low-frequency hearing loss, aural fullness, tinnitus without significant vertigo. Isolated cochlear hydrops is more common in males, average age in mid-60's and there is a low comorbidity of migraine headaches. This contrasts significantly with patients with isolated saccular hydrops on MRI from our prior studies. We believe that isolated cochlear EH with hearing loss but no vertigo is distinct from Meniere's disease or its variant delayed endolymphatic hydrops. We propose that cochlear Meniere's disease represents a distinct clinical entity that could be a variant of Meniere's disease.
Risk Factors of Central Lymph Node Metastasis in Papillary Thyroid Microcarcinoma and the Value of Sentinel Lymph Node Biopsy
Authors: Zhao Jing , Zhao Ye , Ling Yuwei , Kang Hua
Published: June 2021

Objective: The present study aims to investigate the risk factors of central lymph node metastasis (CNM) in papillary thyroid microcarcinoma (PTMC) and evaluate the predictive value of sentinel lymph node biopsy (SLNB) during surgery.

Methods: The clinicopathological data of 179 patients with PTMC staging in cN0 and with SLNB performed were analyzed retrospectively. Positive sentinel lymph node ratio (PSLNR) and additional positive lymph node (APLN) were analyzed in cases with positive SLNB. The efficiency of SLNB was investigated. ROC curves were plotted to evaluate the predictive value of PSLNR for APLN.

Results: Cumulative maximum diameter of tumors (CMD) (P = 0.041) and capsule involvement (CI) (P = 0.014) were independent risk factors for central lymph node metastasis. The SLNB success rate was 97.28%, and the incidence of CNM was 31.28%. The sensitivity, specificity, false positive rate (FPR), false negative rate (FNR), positive predictive value (PPV), and negative predictive value (NPV) of SLNB to evaluate CNM and APLN were 82.14 vs. 61.54%, 100 vs. 80.39%, 0 vs. 19.61%, 17.86 vs. 38.46%, 100 vs. 34.78%, and 92.48 vs. 92.48%, respectively. For cases with positive SLNB, subgroup analysis was performed according to APLN. The PSLNRs of true and false positive groups were 0.4620 ± 0.1744 and 0.2425 ± 0.1355, respectively (P < 0.001). Analyzing the predictive value of PSLNR by the ROC curve, the optimal diagnostic cutoff point was 0.2917 [AUC = 0.861 (95% CI: 0.757, 0.966), P < 0.001], and the sensitivity, specificity, FPR, FNR, PPV, and NPV of PSLNR were 87.50, 73.33, 26.67, 12.50, 63.64, and 91.67%, respectively.

Conclusion: CMD and CI are independent risk factors for central lymph node metastasis in PTMC. SLNB has good predictive value for CNM. For cases with positive SLNB, PSLNR could be used to predict the presence of APLN, which may provide a theoretical basis for intraoperative lymph node dissection.
Feline Stool-Associated Circular DNA Virus (FeSCV) in Diarrheic Cats in China
Authors: Hao Xiangqi , Li Yanchao , Hu Xinkai , Fu Xueying , Dong Jie , Zhang Haoyang , Zhou Pei , Li Shoujun
Published: June 2021

Feline stool-associated circular DNA virus (FeSCV) is an unclassified circular replication-associated protein-encoding single-stranded (CRESS) DNA virus that was discovered in cats in Japan in 2018. Few studies on the genomic characteristics and prevalence of FeSCV have been conducted. To investigate whether FeSCV has been circulating in domestic cats in Guangdong, China, fecal samples were collected from cats with diarrhea in an animal hospital in 2018 to promote research on FeSCV. The FeSCV genome was obtained by PCR amplification and sequencing, and the detected virus was named PY4 (GenBank No. MT732515). The genome of PY4 was 2,034 nt in size, which was 12 nt smaller than the reported genome of Japanese FeSCV strains (KU7, KU8, KU9, KU14) (2,046 nt). The PY4 strain shared 95.1 ~ 95.5% homology with Japanese FeSCV strains. Notably, the Cap protein of PY4 was mutated at 15 amino acid sites, and the PY4 genome contained a unique open reading frame 3. In addition, there were two additional base insertions in the stem-loop structure of PY4, and the nucleotide homology of the spacer region was not high. A phylogenetic tree based on Rep proteins showed that PY4, Japanese FeSCVs and rodent stool-associated circular viruses (RodSCVs) clustered together, suggesting that they might share a similar origin in their phylogenetic evolution. In this study, samples collected in Guangzhou, China, in 2018 were subjected to an etiological investigation, and 20% (2/10) of the samples were positive for FeSCV. The ORFs, stem-loop structures, Cap proteins and intergenic region sequences of PY4 were significantly different from those reported in Japan. This is the first report of FeSCV in domestic cats with diarrhea in China, and further epidemiological studies are urgently needed to assess the impact of the virus on cats.
Promoting Physical Activity and Reducing Sedentary Behaviors among French Adolescent Girls from Low-Incomes Communities
Authors: Nicaise Virginie , Martinent Guillaume , Rauseo Bethania , Guillet-Descas Emma
Published: June 2021

(1) Background: Despite health benefits of engaging in regular physical activity (PA), adolescents fail to achieve the recommended PA practice (especially among girls with low socio-economic position). Researchers have been prompted to adopt models of social cognition to help identify the role of psychological factors in influencing PA and sedentary behaviors. Thus, this study examined the effects of an intervention promoting PA, reducing sedentary activity among adolescent girls from low-incomes communities, and explored the relationships between core constructs of salient theoretical frameworks (self-determination theory, theory of planned behavior, implicit and explicit attitude towards PA, and sedentary behaviors); (2) Methods: An intervention was delivered to 28 adolescent girls. They reported their scores on a variety of core psychological constructs grounded within the aforementioned theoretical frameworks as well as on several outcomes, such as objective PA (pedometers) and perceived mental and physical health. These scores were gathered both before and after the 8-weeks program; (3) Results: Results revealed changes on external regulation and implicit attitudes toward sedentary behaviors from before to after the program. However, objective PA behavior did not change; (4) Conclusions: Future studies are encouraged to further explore mechanisms of behavior change derived from integrated and socio-ecological theories.
Enhancing Kidney Vasculature in Tissue Engineering—Current Trends and Approaches: A Review
Authors: Lebedenko Charlotta G. , Banerjee Ipsita A.
Published: June 2021

Chronic kidney diseases are a leading cause of fatalities around the world. As the most sought-after organ for transplantation, the kidney is of immense importance in the field of tissue engineering. The primary obstacle to the development of clinically relevant tissue engineered kidneys is precise vascularization due to the organ’s large size and complexity. Current attempts at whole-kidney tissue engineering include the repopulation of decellularized kidney extracellular matrices or vascular corrosion casts, but these approaches do not eliminate the need for a donor organ. Stem cell-based approaches, such as kidney organoids vascularized in microphysiological systems, aim to construct a kidney without the need for organ donation. These organ-on-a-chip models show complex, functioning kidney structures, albeit at a small scale. Novel methodologies for developing engineered scaffolds will allow for improved differentiation of kidney stem cells and organoids into larger kidney grafts with clinical applications. While currently, kidney tissue engineering remains mostly limited to individual renal structures or small organoids, further developments in vascularization techniques, with technologies such as organoids in microfluidic systems, could potentially open doors for a large-scale growth of whole engineered kidneys for transplantation.
The Fear to Move in a Crowded Environment. Poor Spatial Memory Related to Agoraphobic Disorder
Authors: Zucchelli Micaela Maria , Piccardi Laura , Nori Raffaella
Published: June 2021

Individuals with agoraphobia exhibit impaired exploratory activity when navigating unfamiliar environments. However, no studies have investigated the contribution of visuospatial working memory (VSWM) in these individuals’ ability to acquire and process spatial information while considering the use of egocentric and allocentric coordinates or environments with or without people. A total of 106 individuals (53 with agoraphobia and 53 controls) navigated in a virtual square to acquire spatial information that included the recognition of landmarks and the relationship between landmarks and themselves (egocentric coordinates) and independent of themselves (allocentric coordinates). Half of the participants in both groups navigated in a square without people, and half navigated in a crowded square. They completed a VSWM test in addition to tasks measuring landmark recognition and egocentric and allocentric judgements concerning the explored square. The results showed that individuals with agoraphobia had reduced working memory only when active processing of spatial elements was required, suggesting that they exhibit spatial difficulties particularly in complex spatial tasks requiring them to process information simultaneously. Specifically, VSWM deficits mediated the relationship between agoraphobia and performance in the allocentric judgements. The results are discussed considering the theoretical background of agoraphobia in order to provide useful elements for the early diagnosis of this disorder.
Biologically-Based Mathematical Modeling of Tumor Vasculature and Angiogenesis via Time-Resolved Imaging Data
Authors: Hormuth David A. , Phillips Caleb M. , Wu Chengyue , Lima Ernesto A. B. F. , Lorenzo Guillermo , Jha Prashant K. , Jarrett Angela M. , Oden J. Tinsley , Yankeelov Thomas E.
Published: June 2021

Tumor-associated vasculature is responsible for the delivery of nutrients, removal of waste, and allowing growth beyond 2–3 mm3. Additionally, the vascular network, which is changing in both space and time, fundamentally influences tumor response to both systemic and radiation therapy. Thus, a robust understanding of vascular dynamics is necessary to accurately predict tumor growth, as well as establish optimal treatment protocols to achieve optimal tumor control. Such a goal requires the intimate integration of both theory and experiment. Quantitative and time-resolved imaging methods have emerged as technologies able to visualize and characterize tumor vascular properties before and during therapy at the tissue and cell scale. Parallel to, but separate from those developments, mathematical modeling techniques have been developed to enable in silico investigations into theoretical tumor and vascular dynamics. In particular, recent efforts have sought to integrate both theory and experiment to enable data-driven mathematical modeling. Such mathematical models are calibrated by data obtained from individual tumor-vascular systems to predict future vascular growth, delivery of systemic agents, and response to radiotherapy. In this review, we discuss experimental techniques for visualizing and quantifying vascular dynamics including magnetic resonance imaging, microfluidic devices, and confocal microscopy. We then focus on the integration of these experimental measures with biologically based mathematical models to generate testable predictions.
Upper Aerodigestive Tract Squamous Cell Carcinomas Show Distinct Overall DNA Methylation Profiles and Different Molecular Mechanisms behind WNT Signaling Disruption
Authors: Soares-Lima Sheila Coelho , Mehanna Hisham , Camuzi Diego , de Souza-Santos Paulo Thiago , Simão Tatiana de Almeida , Nicolau-Neto Pedro , Almeida Lopes Monique de Souza , Cuenin Cyrille , Talukdar Fazlur Rahman , Batis Nikolaos , Costa Izabella , Dias Fernando , Degli Esposti Davide , Boroni Mariana , Herceg Zdenko , Ribeiro Pinto Luis Felipe
Published: June 2021

Upper aerodigestive tract (UADT) tumors present different biological behavior and prognosis, suggesting specific molecular mechanisms underlying their development. However, they are rarely considered as single entities (particularly head and neck subsites) and share the most common genetic alterations. Therefore, there is a need for a better understanding of the global DNA methylation differences among UADT tumors. We performed a genome-wide DNA methylation analysis of esophageal (ESCC), laryngeal (LSCC), oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas, and their non-tumor counterparts. The unsupervised analysis showed that non-tumor tissues present markedly distinct DNA methylation profiles, while tumors are highly heterogeneous. Hypomethylation was more frequent in LSCC and OPSCC, while ESCC and OSCC presented mostly hypermethylation, with the latter showing a CpG island overrepresentation. Differentially methylated regions affected genes in 127 signaling pathways, with only 3.1% of these being common among different tumor subsites, but with different genes affected. The WNT signaling pathway, known to be dysregulated in different epithelial tumors, is a frequent hit for DNA methylation and gene expression alterations in ESCC and OPSCC, but mostly for genetic alterations in LSCC and OSCC. UADT tumor subsites present differences in genome-wide methylation regarding their profile, intensity, genomic regions and signaling pathways affected.
Cancer Epigenetic Biomarkers in Liquid Biopsy for High Incidence Malignancies
Authors: Palanca-Ballester Cora , Rodriguez-Casanova Aitor , Torres Susana , Calabuig-Fariñas Silvia , Exposito Francisco , Serrano Diego , Redin Esther , Valencia Karmele , Jantus-Lewintre Eloisa , Diaz-Lagares Angel , Montuenga Luis , Sandoval Juan , Calvo Alfonso
Published: June 2021

Early alterations in cancer include the deregulation of epigenetic events such as changes in DNA methylation and abnormal levels of non-coding (nc)RNAs. Although these changes can be identified in tumors, alternative sources of samples may offer advantages over tissue biopsies. Because tumors shed DNA, RNA, and proteins, biological fluids containing these molecules can accurately reflect alterations found in cancer cells, not only coming from the primary tumor, but also from metastasis and from the tumor microenvironment (TME). Depending on the type of cancer, biological fluids encompass blood, urine, cerebrospinal fluid, and saliva, among others. Such samples are named with the general term “liquid biopsy” (LB). With the advent of ultrasensitive technologies during the last decade, the identification of actionable genetic alterations (i.e., mutations) in LB is a common practice to decide whether or not targeted therapy should be applied. Likewise, the analysis of global or specific epigenetic alterations may also be important as biomarkers for diagnosis, prognosis, and even for cancer drug response. Several commercial kits that assess the DNA promoter methylation of single genes or gene sets are available, with some of them being tested as biomarkers for diagnosis in clinical trials. From the tumors with highest incidence, we can stress the relevance of DNA methylation changes in the following genes found in LB: SHOX2 (for lung cancer); RASSF1A, RARB2, and GSTP1 (for lung, breast, genitourinary and colon cancers); and SEPT9 (for colon cancer). Moreover, multi-cancer high-throughput methylation-based tests are now commercially available. Increased levels of the microRNA miR21 and several miRNA- and long ncRNA-signatures can also be indicative biomarkers in LB. Therefore, epigenetic biomarkers are attractive and may have a clinical value in cancer. Nonetheless, validation, standardization, and demonstration of an added value over the common clinical practice are issues needed to be addressed in the transfer of this knowledge from “bench to bedside”.
Metabolic Anti-Cancer Effects of Melatonin: Clinically Relevant Prospects
Authors: Samec Marek , Liskova Alena , Koklesova Lenka , Zhai Kevin , Varghese Elizabeth , Samuel Samson Mathews , Šudomová Miroslava , Lucansky Vincent , Kassayova Monika , Pec Martin , Biringer Kamil , Brockmueller Aranka , Kajo Karol , Hassan Sherif T. S. , Shakibaei Mehdi , Golubnitschaja Olga , Büsselberg Dietrich , Kubatka Peter
Published: June 2021

Metabolic reprogramming characterized by alterations in nutrient uptake and critical molecular pathways associated with cancer cell metabolism represents a fundamental process of malignant transformation. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone secreted by the pineal gland. Melatonin primarily regulates circadian rhythms but also exerts anti-inflammatory, anti-depressant, antioxidant and anti-tumor activities. Concerning cancer metabolism, melatonin displays significant anticancer effects via the regulation of key components of aerobic glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP) and lipid metabolism. Melatonin treatment affects glucose transporter (GLUT) expression, glucose-6-phosphate dehydrogenase (G6PDH) activity, lactate production and other metabolic contributors. Moreover, melatonin modulates critical players in cancer development, such as HIF-1 and p53. Taken together, melatonin has notable anti-cancer effects at malignancy initiation, progression and metastasing. Further investigations of melatonin impacts relevant for cancer metabolism are expected to create innovative approaches supportive for the effective prevention and targeted therapy of cancers.
NF-Y Subunits Overexpression in HNSCC
Authors: Bezzecchi Eugenia , Bernardini Andrea , Ronzio Mirko , Miccolo Claudia , Chiocca Susanna , Dolfini Diletta , Mantovani Roberto
Published: June 2021

NF-Y is the CCAAT-binding trimer formed by the histone fold domain (HFD), NF-YB/NF-YC and NF-YA. The CCAAT box is generally prevalent in promoters of “cancer” genes. We reported the overexpression of NF-YA in BRCA, LUAD and LUSC, and of all subunits in HCC. Altered splicing of NF-YA was found in breast and lung cancer. We analyzed RNA-seq datasets of TCGA and cell lines of head and neck squamous cell carcinomas (HNSCC). We partitioned all TCGA data into four subtypes, deconvoluted single-cell RNA-seq of tumors and derived survival curves. The CCAAT box was enriched in the promoters of overexpressed genes. The “short” NF-YAs was overexpressed in all subtypes and the “long” NF-YAl in Mesenchymal. The HFD subunits are overexpressed, except Basal (NF-YB) and Atypical (NF-YC); NF-YAl is increased in p53 mutated tumors. In HPV-positive tumors, high levels of NF-YAs, p16 and ΔNp63 correlate with better prognosis. Deconvolution of single cell RNA-seq (scRNA-seq) found a correlation of NF-YAl with Cancer Associated Fibroblasts (CAFs) and p-EMT cells, a population endowed with metastatic potential. We conclude that overexpression of HFD subunits and NF-YAs is protective in HPV-positive tumors; expression of NF-YAl is largely confined to mutp53 tumors and malignant p-EMT cells.
Splenic Volume as a Surrogate Marker of Immune Checkpoint Inhibitor Efficacy in Metastatic Non Small Cell Lung Cancer
Authors: Galland Loïck , Lecuelle Julie , Favier Laure , Fraisse Cléa , Lagrange Aurélie , Kaderbhai Courèche , Truntzer Caroline , Ghiringhelli François
Published: June 2021

Monoclonal antibodies targeting PD1/PD-L1 are game changers in advanced non-small cell lung cancer (NSCLC), but biomarkers are lacking. We previously reported the prognostic role of splenic volume in digestive cancer and its correlation with the presence of immunosuppressive cells. The aim of this study was to evaluate the prognostic role of splenic volume in NSCLC patients treated with immune checkpoint inhibitors (ICIs). We conducted a retrospective study of 276 patients receiving ICIs for advanced NSCLC in the Georges François Leclerc Cancer Center. The association between splenic volume at baseline and at two months of therapy and progression-free survival (PFS) during ICI treatment or overall survival (OS) from ICI initiation was evaluated using univariate and multivariable Cox analyses. Splenic volume during treatment and the change in splenic volume were associated with poor PFS (respectively p = 0.02 and p = 0.001) and with OS (respectively p < 1.10−3 and p < 1.10−3). Baseline splenic volume at the first evaluation was also associated with poor OS (p = 0.001). LDH rate and dNLR were positively correlated with splenic volume, as well as with its evolution. After the adjustment of clinical variables, splenic volumes remained a predictive marker of immunotherapy efficacy. Splenic volume is a prognostic biomarker in patients with advanced NSCLC treated with ICIs.
Quercetin Induces Anticancer Activity by Upregulating Pro-NAG-1/GDF15 in Differentiated Thyroid Cancer Cells
Authors: Hong Yukyung , Lee Jaehak , Moon Hyunjin , Ryu Chang H. , Seok Jungirl , Jung Yuh-Seog , Ryu Junsun , Baek Seung J.
Published: June 2021

Although the treatment of thyroid cancer has improved, unnecessary surgeries are performed due to a lack of specific diagnostic and prognostic markers. Therefore, the identification of novel biomarkers should be considered in the diagnosis and treatment of thyroid cancer. In this study, antibody arrays were performed using tumor and adjacent normal tissues of patients with papillary thyroid cancer, and several potential biomarkers were identified. Among the candidate proteins chosen based on the antibody array data, mature NAG-1 exhibited increased expression in tumor tissues compared to adjacent normal tissues. In contrast, pro-NAG-1 expression increased in normal tissues, as assessed by western blot analysis. Furthermore, pro-NAG-1 expression was increased when the thyroid cancer cells were treated with phytochemicals and nonsteroidal anti-inflammatory drugs in a dose-dependent manner. In particular, quercetin highly induced the expression of pro-NAG-1 but not that of mature NAG-1, with enhanced anticancer activity, including apoptosis induction and cell cycle arrest. Examination of the NAG-1 promoter activity showed that p53, C/EBPα, or C/EBPδ played a role in quercetin-induced NAG-1 expression. Overall, our study indicated that NAG-1 may serve as a novel biomarker for thyroid cancer prognosis and may be used as a therapeutic target for thyroid cancers.
Recent Advances in Mobile Ad Hoc Networks
Authors: Kadoch Michel
Published: June 2021

Mobile ad hoc networks (MANETs) represent a featured domain of wireless networks, which are well-differentiated from cellular network infrastructure and have attracted decades of research effort [...]