bluuebunny/crossref_metadata_2025 huggingface dataset:
Fear and Coping in Students during the Early Stages of the COVID-19 Pandemic: A Combined Cross-Sectional and Longitudinal Study
Authors: Hasratian Anni M. , Nordberg Hannah O. , Meuret Alicia E. , Ritz Thomas
Published: June 2021

The overwhelming impacts of the COVID-19 pandemic have been experienced by individuals across the world. Additional circumstances unique to students affected their studies during the early stages of the pandemic, with changes in living and studying mid-semester. The current study aimed to investigate predictors of fear of COVID-19 in college students during this acute phase using cross-sectional and longitudinal samples. In total, 175 undergraduate students completed an online questionnaire in the spring 2020 semester following lockdown. A subset of 58 students completed a separate survey in fall 2019, which served as a baseline. For the cross-sectional sample, pre-COVID-19 and current living situations did not predict COVID-19 fears. However, a propensity to experience panic was significantly associated with greater COVID-19 fears. How students coped with the pandemic was not associated with COVID-19 fears, although a greater propensity to use denial as a coping style tended to be related to greater COVID-19 fears. In the longitudinal subsample, students showed decreased positive mood and social stress load while depressive mood increased after lockdown. Their preferred coping styles changed, utilizing more self-distraction and acceptance, and less self-blame and substance use. Findings reflect both positive and negative consequences of the pandemic. The unique changes in students’ lifestyles will need to be met by tailored interventions.
Pollution Haven Hypothesis of Global CO2, SO2, NOx—Evidence from 43 Economies and 56 Sectors
Authors: Zhang Ke , Wang Xingwei
Published: June 2021

With the development of trade liberalization, the pollutants emissions embodied in global trade are increasing. The pollution haven hypothesis caused by trade has aroused wide attention. The fragmentation of international production has reshaped trade patterns. The proportion of intermediate product trade in global trade is increasing. However, little has been done to study the pollution haven of different pollutants under different trade patterns. In this paper, major environmental pollutants CO2 (carbon dioxide), SO2 (sulfur dioxide), and NOx (nitrogen oxides) are selected as the research objects. This study investigated the global pollution haven phenomenon in 43 countries and 56 major industries from 2000 to 2014. Based on the MRIO model, the trade mode is divided into three specific patterns: final product trade, intermediate product trade in the last stage of production, and the trade related to the global value chain. The results show that trade liberalization could reduce global CO2, SO2, and NOx emissions, and intermediate product trade has a more significant emission reduction effect than final product trade. Trade’s impacts on each country are various, and the main drivers are also different. For example, the European Union avoids becoming a pollution haven mainly through the trade related to the global value chain. The suppressed emissions under this trade pattern are 71.8 Mt CO2, 2.2 Mt SO2, 2.2 Mt NOx. India avoids most pollutants emissions through intermediate product trade. China has become the most serious pollution haven through final product trade. The trade pattern could increase China 829.4 Mt CO2, 4.5 Mt SO2, 2.6 Mt NOx emissions in 2014.
Victimization as a Result of Non-Consensual Dissemination of Sexting and Psychopathology Correlates: An Exploratory Analysis
Authors: Gassó Aina M. , Mueller-Johnson Katrin , Gómez-Durán Esperanza L.
Published: June 2021

Sexting is generally known as creating, sending and/or forwarding of sexual content using electronic devices. When such content is non-consensually disseminated, it becomes a criminally relevant behavior. To date, very few empirical studies have examined the prevalence of non-consensual dissemination of sexting, and none of them have analyzed the relationship with psychopathology and further victimization outcomes. Therefore, the aims of this study were (1) to examine the prevalence of non-consensual dissemination of sexual content, (2) to analyze the prevalence of further victimization as a result of non-consensual dissemination of sexting and (3) to investigate the association between secondary victimization as a result of non-consensual dissemination of sexting and psychopathology. The sample comprised 1370 Spanish college students (73.6% female; mean age = 21.4 years; SD = 4.85) who answered an online survey about their engagement in sexting behaviors, online sexual victimization and psychopathology, measured by a sexting scale and the Listado de Síntomas Breve (LSB-50), respectively. Overall, 43 participants (3.14) were victims of non-consensual dissemination of sexting, and results showed those participants who had suffered further victimization reported higher psychopathology scores than those who were not victimized and that being victimized by an ex-partner was associated with poorer mental health outcomes in the victim. Further implications are discussed.
Predictive Utility of Changes in Optic Nerve Sheath Diameter after Cardiac Arrest for Neurologic Outcomes
Authors: Lee Heekyung , Lee Joonkee , Shin Hyungoo , Kim Changsun , Choi Hyuk-Joong , Kang Bo-Seung
Published: June 2021

The optic nerve sheath diameter (ONSD) can help predict the neurologic outcomes of patients with post-cardiac arrest (CA) return of spontaneous circulation (ROSC). We aimed to investigate the effect of ONSD changes before and after CA on neurologic outcomes in patients with ROSC after CA using brain computed tomography (CT). The study included patients hospitalized after CA, who had undergone pre- and post-CA brain CT between January 2001 and September 2020. The patients were divided into good and poor neurologic outcome (GNO and PNO, respectively) groups based on their neurologic outcome at hospital discharge. We performed between-group comparisons of the amount and rate of ONSD changes in brain CT and calculated the area under the curve (AUC) to determine their predictive value for neurologic outcomes. Among the 96 enrolled patients, 25 had GNO. Compared with the GNO group, the PNO group showed a significantly higher amount (0.30 vs. 0.63 mm; p = 0.030) and rate (5.26 vs. 12.29%; p = 0.041) of change. The AUC for predicting PNO was 0.64 (95% confidence interval = 0.53–0.73; p = 0.04), and patients with a rate of ONSD change >27.2% had PNO with 100% specificity and positive predictive value. Hence, ONSD changes may predict neurologic outcomes in patients with post-CA ROSC.
Relationships of Bone Mineral Variables with Body Composition, Blood Hormones and Training Volume in Adolescent Female Athletes with Different Loading Patterns
Authors: Tamolienė Vita , Remmel Liina , Gruodyte-Raciene Rita , Jürimäe Jaak
Published: June 2021

The aim of this investigation was to determine the relationships of areal bone mineral density (aBMD) and content (BMC) with body composition, blood hormone and training load variables in adolescent female athletes with different loading patterns. The participants were 73 healthy adolescent females (14–18 years), who were divided into three groups: rhythmic gymnasts (RG; n = 33), swimmers (SW; n = 20) and untrained controls (UC; n = 20). Bone mineral and body compositional variables were measured by dual-energy X-ray absorptiometry, and insulin-like growth factor-1 (IGF-1), estradiol and leptin were analyzed from blood samples. In addition, aerobic performance was assessed by a peak oxygen consumption test. No differences (p > 0.05) in weekly training volume were observed between rhythmic gymnasts (17.6 ± 5.3 h/week) and swimmers (16.1 ± 6.9 h/week). Measured areal bone mineral density and bone mineral content values were higher in rhythmic gymnasts compared with other groups (p < 0.05), while no differences (p > 0.05) in measured bone mineral values were seen between swimmers and untrained control groups. Multiple regression models indicated that IGF-1 alone explained 14% of the total variance (R2 × 100) in lumbar spine aBMD, while appendicular muscle mass and training volume together explained 37% of the total variance in femoral neck BMC in the rhythmic gymnast group only. In swimmers, age at menarche, estradiol and appendicular muscle mass together explained 68% of the total variance in lumbar spine BMC, while appendicular muscle mass was the only predictor and explained 19 to 53% of the total variance in measured bone mineral values in untrained controls. In conclusion, adolescent rhythmic gymnasts with specific weight-bearing athletic activity present higher areal bone mineral values in comparison with swimmers and untrained controls. Specific training volume together with appendicular muscle mass influenced cortical bone development at the femoral neck site of the skeleton in rhythmic gymnasts, while hormonal values influenced trabecular bone development at the lumbar spine site in both athletic groups with different loading patterns.
COVID-19 Changed the Incidence and the Pattern of Pediatric Traumas: A Single-Centre Study in a Pediatric Emergency Department
Authors: Ruzzini Laura , De Salvatore Sergio , Lamberti Daniela , Maglione Pierluigi , Piergentili Ilaria , Crea Francesca , Ossella Chiara , Costici Pier Francesco
Published: June 2021

The first wave of COVID-19 spread worldwide from March to May 2020. Italy was one of the countries in the world where the lockdown period was most prolonged and restrictive. To date, the impact of prolonged lockdown on pediatric traumas has not fully investigated. This paper aimed to analyze, and compare to 2019, the incidence and the fracture pattern in patients admitted to our pediatric hospital during the total lockdown period. A single-center retrospective study was performed. The data were gathered from the Pediatric Emergency Department (PED) of the Bambino Gesù Children Hospital of Rome (Palidoro). This PED is the pediatric referral center for Rome and the hub for pediatric traumas of the region. Any admission diagnosis for fracture, trauma, sprains and dislocation during the lockdown period (10 March–4 May) were included. The demographic data, diagnosis, type of treatment, fracture segment, bone involvement and time interval between trauma and presentation to the PED were recorded. In 2020, a reduction of total traumas and fractures, compared to 2019 (p < 0.001), occurred (81%). Superior limb and inferior limb fractures decreased in 2020 compared to 2019 (p < 0.05). The identification of pediatric traumas and fractures trend could be useful to reorganize the PED. Epidemiological data from the previous lockdown could be helpful to prepare the healthcare system for new pandemic waves. Moreover, sharing national statistics and correlating those to other countries’ protocols, could be helpful to solve problems in case of worldwide emergency situations.
Combining Kangaroo Care and Live-Performed Music Therapy: Effects on Physiological Stability and Neurological Functioning in Extremely and Very Preterm Infants
Authors: Span Loïs C. , van Dokkum Nienke H. , Ravensbergen Anne-Greet , Bos Arend F. , Jaschke Artur C.
Published: June 2021

Interventions such as kangaroo care (KC) and live-performed music therapy (LPMT), are increasingly used to facilitate stress reduction in neonates. This study aims to investigate the effect of combining the two on physiological responses and neurological functioning in very preterm infants. Infants received six sessions of LPMT. KC was added to one LPMT session. Physiological responses included heart rate, respiratory rate and oxygen saturation. We videotaped infants for 30 min before and after two sessions to assess general movements (GMs). We included 17 infants, gestational age median 26.0 weeks (IQR 25.6–30.6 weeks), of whom six were males. Combined interventions showed a decrease in heart rate from mean 164 bpm before to 157 bpm during therapy, p = 0.001. Oxygen saturation levels increased during combination therapy from median 91.4% to 94.5%, p = 0.044. We found no effects of LPMT or combined interventions on GMs. Infants with a postnatal age (PNA) <7 days generally seem to display less optimal GMs after therapy compared with infants with a PNA >7 days. In conclusion, combining interventions is equally beneficial for physiological stability and neurological functioning as LPMT alone. Future studies should focus on the effects of this combination on parent-infant bonding.
A Model for Risk Prediction of Cerebrovascular Disease Prevalence—Based on Community Residents Aged 40 and above in a City in China
Authors: Zhu Qin , Luo Die , Zhou Xiaojun , Cai Xianxu , Li Qi , Lu Yuanan , Chen Jiayan
Published: June 2021

Cerebrovascular disease (CVD) is the leading cause of death in many countries including China. Early diagnosis and risk assessment represent one of effective approaches to reduce the CVD-related mortality. The purpose of this study was to understand the prevalence and influencing factors of cerebrovascular disease among community residents in Qingyunpu District, Nanchang City, Jiangxi Province, and to construct a model of cerebrovascular disease risk index suitable for local community residents. A stratified cluster sampling method was used to sample 2147 community residents aged 40 and above, and the prevalence of cerebrovascular diseases and possible risk factors were investigated. It was found that the prevalence of cerebrovascular disease among local residents was 4.5%. Poisson regression analysis found that old age, lack of exercise, hypertension, diabetes, smoking, and family history of cerebrovascular disease are the main risk factors for local cerebrovascular disease. The relative risk ORs were 3.284, 2.306, 2.510, 3.194, 1.949, 2.315, respectively. For these six selected risk factors, a cerebrovascular disease risk prediction model was established using the Harvard Cancer Index method. The R value of the risk prediction model was 1.80 (sensitivity 81.8%, specificity 47.0%), which was able to well predict the risk of cerebrovascular disease among local residents. This provides a scientific basis for the further development of local cerebrovascular disease prevention and control work.
Developmental Hip Dysplasia: An Epidemiological Nationwide Study in Italy from 2001 to 2016
Authors: Longo Umile Giuseppe , Papalia Rocco , De Salvatore Sergio , Ruzzini Laura , Piergentili Ilaria , Oggiano Leonardo , Costici Pier Francesco , Denaro Vincenzo
Published: June 2021

Developmental Dysplasia of the Hip (DDH) includes a broad spectrum of hip abnormalities. DDH requires early diagnosis and treatment; however, no international consensus on screening protocol and treatment is provided in the literature. Epidemiological studies are helpful to understand the national variation of a specific surgical procedure and compare it with that of other countries. Data provided by different countries could allow researchers to provide international guidelines for DDH screening and treatment. Limited data are reported regarding trends of hospitalization for DDH, and no public database is available. The purpose of this study was to estimate annual admissions for DDH in Italian patients from 2001 to 2016, based on the hospitalization reports. Data of this study were collected from the National Hospital Discharge Reports (SDO) reported at the Italian Ministry of Health. Descriptive statistical analyses were performed. From 2001 to 2016, 3103 hospitalizations for DDH were recorded in Italy, with a mean incidence of 2.33 (per 100,000 young inhabitants). Females of the 0–4 years old group represented the majority of patients hospitalized for DDH.
Human α-Galactosidase A Mutants: Priceless Tools to Develop Novel Therapies for Fabry Disease
Authors: Modrego Andrea , Amaranto Marilla , Godino Agustina , Mendoza Rosa , Barra José Luis , Corchero José Luis
Published: June 2021

Fabry disease (FD) is a lysosomal storage disease caused by mutations in the gene for the α-galactosidase A (GLA) enzyme. The absence of the enzyme or its activity results in the accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3), in different tissues, leading to a wide range of clinical manifestations. More than 1000 natural variants have been described in the GLA gene, most of them affecting proper protein folding and enzymatic activity. Currently, FD is treated by enzyme replacement therapy (ERT) or pharmacological chaperone therapy (PCT). However, as both approaches show specific drawbacks, new strategies (such as new forms of ERT, organ/cell transplant, substrate reduction therapy, or gene therapy) are under extensive study. In this review, we summarize GLA mutants described so far and discuss their putative application for the development of novel drugs for the treatment of FD. Unfavorable mutants with lower activities and stabilities than wild-type enzymes could serve as tools for the development of new pharmacological chaperones. On the other hand, GLA mutants showing improved enzymatic activity have been identified and produced in vitro. Such mutants could overcome several complications associated with current ERT, as lower-dose infusions of these mutants could achieve a therapeutic effect equivalent to that of the wild-type enzyme.
Dysregulated Expression of Arterial MicroRNAs and Their Target Gene Networks in Temporal Arteries of Treatment-Naïve Patients with Giant Cell Arteritis
Authors: Kuret Tadeja , Lakota Katja , Čučnik Saša , Jurčič Vesna , Distler Oliver , Rotar Žiga , Hočevar Alojzija , Sodin-Šemrl Snežna , Frank-Bertoncelj Mojca
Published: June 2021

In this study, we explored expression of microRNA (miR), miR-target genes and matrix remodelling molecules in temporal artery biopsies (TABs) from treatment-naïve patients with giant cell arteritis (GCA, n = 41) and integrated these analyses with clinical, laboratory, ultrasound and histological manifestations of GCA. NonGCA patients (n = 4) served as controls. GCA TABs exhibited deregulated expression of several miRs (miR-21-5p, -145-5p, -146a-5p, -146b-5p, -155-5p, 424-3p, -424-5p, -503-5p), putative miR-target genes (YAP1, PELI1, FGF2, VEGFA, KLF4) and matrix remodelling factors (MMP2, MMP9, TIMP1, TIPM2) with key roles in Toll-like receptor signaling, mechanotransduction and extracellular matrix biology. MiR-424-3p, -503-5p, KLF4, PELI1 and YAP1 were identified as new deregulated molecular factors in GCA TABs. Quantities of miR-146a-5p, YAP1, PELI1, FGF2, TIMP2 and MMP9 were particularly high in histologically positive GCA TABs with occluded temporal artery lumen. MiR-424-5p expression in TABs and the presence of facial or carotid arteritis on ultrasound were associated with vision disturbances in GCA patients. Correlative analysis of miR-mRNA quantities demonstrated a highly interrelated expression network of deregulated miRs and mRNAs in temporal arteries and identified KLF4 as a candidate target gene of deregulated miR-21-5p, -146a-5p and -155-5p network in GCA TABs. Meanwhile, arterial miR and mRNA expression did not correlate with constitutive symptoms and signs of GCA, elevated markers of systemic inflammation nor sonographic characteristics of GCA. Our study provides new insights into GCA pathophysiology and uncovers new candidate biomarkers of vision impairment in GCA.
Environmental Factors Affecting Thyroid-Stimulating Hormone and Thyroid Hormone Levels
Authors: Babić Leko Mirjana , Gunjača Ivana , Pleić Nikolina , Zemunik Tatijana
Published: June 2021

Thyroid hormones are necessary for the normal functioning of physiological systems. Therefore, knowledge of any factor (whether genetic, environmental or intrinsic) that alters the levels of thyroid-stimulating hormone (TSH) and thyroid hormones is crucial. Genetic factors contribute up to 65% of interindividual variations in TSH and thyroid hormone levels, but many environmental factors can also affect thyroid function. This review discusses studies that have analyzed the impact of environmental factors on TSH and thyroid hormone levels in healthy adults. We included lifestyle factors (smoking, alcohol consumption, diet and exercise) and pollutants (chemicals and heavy metals). Many inconsistencies in the results have been observed between studies, making it difficult to draw a general conclusion about how a particular environmental factor influences TSH and thyroid hormone levels. However, lifestyle factors that showed the clearest association with TSH and thyroid hormones were smoking, body mass index (BMI) and iodine (micronutrient taken from the diet). Smoking mainly led to a decrease in TSH levels and an increase in triiodothyronine (T3) and thyroxine (T4) levels, while BMI levels were positively correlated with TSH and free T3 levels. Excess iodine led to an increase in TSH levels and a decrease in thyroid hormone levels. Among the pollutants analyzed, most studies observed a decrease in thyroid hormone levels after exposure to perchlorate. Future studies should continue to analyze the impact of environmental factors on thyroid function as they could contribute to understanding the complex background of gene–environment interactions underlying the pathology of thyroid diseases.
The Effect of Functional Fiber on Microbiota Composition in Different Intestinal Segments of Obese Mice
Authors: Xu Chuanhui , Liu Jianhua , Gao Jianwei , Wu Xiaoyu , Cui Chenbin , Wei Hongkui , Peng Jian , Zheng Rong
Published: June 2021

The gastrointestinal tract is a heterogeneous ecosystem with distinct, stratified environments, which leads to different microbial composition in different intestinal segments. The regional heterogeneity of intestinal microbiota complicates the relationship between diet and microbiota. Few studies have focused on the effects of different diets on microbiota in different intestinal segments. This study aimed to investigate the effects of functional fiber on the microbial composition in multiple intestinal segments from a high-fat diet compared with a normal chow diet. We found that the response of microbiota from different intestinal segments to diet was related to the intestinal physiologic function and the physicochemical properties of dietary nutrients. A high-fat diet drove changes in the microbial composition in the hindgut, possibly by affecting the digestive environment of the foregut, and increased the regional heterogeneity of the whole intestinal microbiota. The supplementation of functional fiber promoted the microbial transfer and colonization from the anterior to the posterior intestinal segments, and increased the regional similarity of intestinal microbiota accordingly, particularly within the hindgut. The gut fermentation of the functional fiber, which mainly occurred in the hindgut, resulted in a significant change in the microbial composition and metabolism in the cecum and colon, with richer carbohydrate metabolism-related bacteria, including Mucispirillum, Prevotella, Anaerostipes, Oscillospira, Ruminococcus, Bacteroides, Coprococcus, Ruminococcus (Lachnospiraceae), and Allobaculum, and higher production of acetate and butyrate. We concluded that multiple regulatory mechanisms of diets which affect microbiota composition exist, including microbial metabolism, microbial migration, and the regulation of the intestinal environment.
Tumor-Associated Macrophages as Multifaceted Regulators of Breast Tumor Growth
Authors: Munir Maliha Tabassum , Kay Matthew K. , Kang Min H. , Rahman Md Mizanur , Al-Harrasi Ahmed , Choudhury Mahua , Moustaid-Moussa Naima , Hussain Fazle , Rahman Shaikh Mizanoor
Published: June 2021

Breast cancer is the most commonly occurring cancer in women of Western countries and is the leading cause of cancer-related mortality. The breast tumor microenvironment contains immune cells, fibroblasts, adipocytes, mesenchymal stem cells, and extracellular matrix. Among these cells, macrophages or tumor-associated macrophages (TAMs) are the major components of the breast cancer microenvironment. TAMs facilitate metastasis of the breast tumor and are responsible for poor clinical outcomes. High TAM density was also found liable for the poor prognosis of breast cancer. These observations make altering TAM function a potential therapeutic target to treat breast cancer. The present review summarizes the origin of TAMs, mechanisms of macrophage recruitment and polarization in the tumor, and the contributions of TAMs in tumor progression. We have also discussed our current knowledge about TAM-targeted therapies and the roles of miRNAs and exosomes in re-educating TAM function.
Effects of Polymer Blending on the Performance of a Subcutaneous Biodegradable Implant for HIV Pre-Exposure Prophylaxis (PrEP)
Authors: Li Linying , Areson Christine , van der Straten Ariane , Johnson Leah M.
Published: June 2021

Long-acting (LA) HIV pre-exposure prophylaxis (PrEP) can mitigate challenges of adhering to daily or on-demand regimens of antiretrovirals (ARVs). We are developing a subcutaneous implant comprising polycaprolactone (PCL) for sustained delivery of ARVs for PrEP. Here we use tenofovir alafenamide (TAF) as a model drug. Previously, we demonstrated that the release rates of drugs are controlled by the implant surface area and wall thickness, and the molecular weight (MW) of PCL. Here, we further advance the implant design and tailor the release rates of TAF and the mechanical integrity of the implant through unique polymer blend formulations. In vitro release of TAF from the implant exhibited zero-order release kinetics for ~120 days. TAF release rates were readily controlled via the MW of the polymer blend, with PCL formulations of higher MW releasing the drug faster than implants with lower MW PCL. Use of polymer MW to tune drug release rates is partly explained by PCL crystallinity, as higher PCL crystalline material is often associated with a slower release rate. Moreover, results showed the ability to tailor mechanical properties via PCL blends. Blending PCL offers an effective approach for tuning the ARV release rates, implant duration, and integrity, and ultimately the biodegradation profiles of the implant.
Anakinra Activates Superoxide Dismutase 2 to Mitigate Inflammasome Activity
Authors: Pariano Marilena , Pieroni Stefania , De Luca Antonella , Iannitti Rossana G. , Borghi Monica , Puccetti Matteo , Giovagnoli Stefano , Renga Giorgia , D’Onofrio Fiorella , Bellet Marina M. , Stincardini Claudia , Della-Fazia Maria Agnese , Servillo Giuseppe , van de Veerdonk Frank L. , Costantini Claudio , Romani Luigina
Published: June 2021

Inflammasomes are powerful cytosolic sensors of environmental stressors and are critical for triggering interleukin-1 (IL-1)-mediated inflammatory responses. However, dysregulation of inflammasome activation may lead to pathological conditions, and the identification of negative regulators for therapeutic purposes is increasingly being recognized. Anakinra, the recombinant form of the IL-1 receptor antagonist, proved effective by preventing the binding of IL-1 to its receptor, IL-1R1, thus restoring autophagy and dampening NLR family pyrin domain containing 3 (NLRP3) activity. As the generation of mitochondrial reactive oxidative species (ROS) is a critical upstream event in the activation of NLRP3, we investigated whether anakinra would regulate mitochondrial ROS production. By profiling the activation of transcription factors induced in murine alveolar macrophages, we found a mitochondrial antioxidative pathway induced by anakinra involving the manganese-dependent superoxide dismutase (MnSOD) or SOD2. Molecularly, anakinra promotes the binding of SOD2 with the deubiquitinase Ubiquitin Specific Peptidase 36 (USP36) and Constitutive photomorphogenesis 9 (COP9) signalosome, thus increasing SOD2 protein longevity. Functionally, anakinra and SOD2 protects mice from pulmonary oxidative inflammation and infection. On a preclinical level, anakinra upregulates SOD2 in murine models of chronic granulomatous disease (CGD) and cystic fibrosis (CF). These data suggest that protection from mitochondrial oxidative stress may represent an additional mechanism underlying the clinical benefit of anakinra and identifies SOD2 as a potential therapeutic target.
Expression of the E5 Oncoprotein of HPV16 Impacts on the Molecular Profiles of EMT-Related and Differentiation Genes in Ectocervical Low-Grade Lesions
Authors: Ranieri Danilo , French Deborah , Raffa Salvatore , Guttieri Luisa , Torrisi Maria Rosaria , Belleudi Francesca
Published: June 2021

Infection with human papillomavirus type 16 (HPV16) is one of the major risk factors for the development of cervical cancer. Our previous studies have demonstrated the involvement of the early oncoprotein E5 of HPV16 (16E5) in the altered isoform switch of fibroblast growth factor receptor 2 (FGFR2) and the consequent expression in human keratinocytes of the mesenchymal FGFR2c isoform, whose aberrant signaling leads to EMT, invasiveness, and dysregulated differentiation. Here, we aimed to establish the possible direct link between these pathological features or the appearance of FGFR2c and the expression of 16E5 in low-grade squamous intraepithelial lesions (LSILs). Molecular analysis showed that the FGFR2c expression displayed a statistically significant positive correlation with that of the viral oncoprotein, whereas the expression values of the epithelial FGR2b variant, as well as those of the differentiation markers keratin 10 (K10), loricrin (LOR) and involucrin (INV), were inversely linked to the 16E5 expression. In contrast, the expression of EMT-related transcription factors Snail1 and ZEB1 overlapped with that of 16E5, becoming a statistically significant positive correlation in the case of Snail2. Parallel analysis performed in human cervical LSIL-derived W12 cells, containing episomal HPV16, revealed that the depletion of 16E5 by siRNA was able to counteract these molecular events, proving to represent an effective strategy to identify the specific role of this viral oncoprotein in determining LSIL oncogenic and more aggressive profiles. Overall, coupling in vitro approaches to the molecular transcript analysis in ectocervical early lesions could significantly contribute to the characterization of specific gene expression profiles prognostic for those LSILs with a greater probability of direct neoplastic progression.
Efficient Activation of Coal Fly Ash for Silica and Alumina Leaches and the Dependence of Pb(II) Removal Capacity on the Crystallization Conditions of Al-MCM-41
Authors: Zhang Xu , Du Tao , Jia He
Published: June 2021

In this study, four different coal fly ashes (CFAs) were used as raw materials of silica and alumina for the preparation of the alumina-containing Mobil Composition of Matter No. 41 (Al-MCM-41) and the exploration of an activation strategy that is efficient and universal for various CFAs. Alkaline hydrothermal and alkaline fusion activations proceeded at different temperatures to determine the best treatment parameters. We controlled the pore structure and surface hydroxyl density of the CFA-derived Al-MCM-41 by changing the crystallization temperature and aging time. The products were characterized by small-angle X-ray diffraction, nitrogen isotherms, Fourier-transform infrared spectroscopy, 29Si silica magic-angle spinning nuclear magnetic resonance, and transmission electron microscopy, and they were then grafted with thiol groups to remove Pb(II) from aqueous solutions. This paper innovatively evaluates the CFA activation strategies using energy consumption analysis and determines the optimal activation methodology and parameters. This paper also unveils the effect of the crystallization condition of Al-MCM-41 on its subsequent Pb(II) removal capacity. The results show that the appropriate selection of crystallization parameters can considerably increase the removal capacity over Pb(II), providing a new path to tackle the ever-increasing concern of aquic heavy-metal pollution.
A Novel Regulator Participating in Nitrogen Removal Process of Bacillus subtilis JD-014
Authors: Yang Ting , Shi Yi , Yang Qian , Xin Yu , Gu Zhenghua , Zhang Liang
Published: June 2021

Aerobic denitrification is considered as a promising biological method to eliminate the nitrate contaminants in waterbodies. However, the molecular mechanism of this process varies in different functional bacteria. In this study, the nitrogen removal characteristics for a newly isolated aerobic denitrifier Bacillus subtilis JD-014 were investigated, and the potential functional genes involved in the aerobic denitrification process were further screened through transcriptome analysis. JD-014 exhibited efficient denitrification performance when having sodium succinate as the carbon source with the range of nitrate concentration between 50 and 300 mg/L. Following the transcriptome data, most of the up-regulated differentially expressed genes (DEGs) were associated with cell motility, carbohydrate metabolism, and energy metabolism. Moreover, gene nirsir annotated as sulfite reductase was screened out and further identified as a regulator participating in the nitrogen removal process within JD-014. The findings in present study provide meaningful information in terms of a comprehensive understanding of genetic regulation of nitrogen metabolism, especially for Bacillus strains.
Purine Nucleotides Metabolism and Signaling in Huntington’s Disease: Search for a Target for Novel Therapies
Authors: Tomczyk Marta , Glaser Talita , Slominska Ewa M. , Ulrich Henning , Smolenski Ryszard T.
Published: June 2021

Huntington’s disease (HD) is a multi-system disorder that is caused by expanded CAG repeats within the exon-1 of the huntingtin (HTT) gene that translate to the polyglutamine stretch in the HTT protein. HTT interacts with the proteins involved in gene transcription, endocytosis, and metabolism. HTT may also directly or indirectly affect purine metabolism and signaling. We aimed to review existing data and discuss the modulation of the purinergic system as a new therapeutic target in HD. Impaired intracellular nucleotide metabolism in the HD affected system (CNS, skeletal muscle and heart) may lead to extracellular accumulation of purine metabolites, its unusual catabolism, and modulation of purinergic signaling. The mechanisms of observed changes might be different in affected systems. Based on collected findings, compounds leading to purine and ATP pool reconstruction as well as purinergic receptor activity modulators, i.e., P2X7 receptor antagonists, may be applied for HD treatment.
Gastritis, Gastric Polyps and Gastric Cancer
Authors: Waldum Helge , Fossmark Reidar
Published: June 2021

Gastric cancer is still an important disease causing many deaths worldwide, although there has been a marked reduction in prevalence during the last few decades. The decline in gastric cancer prevalence is due to a reduction in Helicobacter pylori infection which has occurred for at least 50 years. The most probable mechanism for the carcinogenic effect of H. pylori is hypergastrinemia since H. pylori infected individuals do not have increased risk of gastric cancer before the development of oxyntic atrophy. When atrophy has developed, the carcinogenic process continues independent of H. pylori. Autoimmune gastritis also induces oxyntic atrophy leading to marked hypergastrinemia and development of ECL cell neoplasia as well as adenocarcinoma. Similarly, long-term treatment with efficient inhibitors of acid secretion like the proton pump inhibitors (PPIs) predisposes to ECL cell neoplasia of a different degree of malignancy. Contrasting the colon where most cancers develop from polyps, most polyps in the stomach have a low malignant potential. Nevertheless, gastric polyps may also give rise to cancer and have some risk factors and mechanisms in common with gastric cancer. In this overview the most common gastric polyps, i.e., hyperplastic polyps, adenomatous polyps and fundic gland polyps will be discussed with respect to etiology and particularly use of PPIs and relation to gastric carcinogenesis.
The Anti-Tumor Activity of the NEDD8 Inhibitor Pevonedistat in Neuroblastoma
Authors: Foster Jennifer H. , Barbieri Eveline , Zhang Linna , Scorsone Kathleen A. , Moreno-Smith Myrthala , Zage Peter , Horton Terzah M.
Published: June 2021

Pevonedistat is a neddylation inhibitor that blocks proteasomal degradation of cullin–RING ligase (CRL) proteins involved in the degradation of short-lived regulatory proteins, including those involved with cell-cycle regulation. We determined the sensitivity and mechanism of action of pevonedistat cytotoxicity in neuroblastoma. Pevonedistat cytotoxicity was assessed using cell viability assays and apoptosis. We examined mechanisms of action using flow cytometry, bromodeoxyuridine (BrDU) and immunoblots. Orthotopic mouse xenografts of human neuroblastoma were generated to assess in vivo anti-tumor activity. Neuroblastoma cell lines were very sensitive to pevonedistat (IC50 136–400 nM). The mechanism of pevonedistat cytotoxicity depended on p53 status. Neuroblastoma cells with mutant (p53MUT) or reduced levels of wild-type p53 (p53si-p53) underwent G2-M cell-cycle arrest with rereplication, whereas p53 wild-type (p53WT) cell lines underwent G0-G1 cell-cycle arrest and apoptosis. In orthotopic neuroblastoma models, pevonedistat decreased tumor weight independent of p53 status. Control mice had an average tumor weight of 1.6 mg + 0.8 mg versus 0.5 mg + 0.4 mg (p < 0.05) in mice treated with pevonedistat. The mechanism of action of pevonedistat in neuroblastoma cell lines in vitro appears p53 dependent. However, in vivo studies using mouse neuroblastoma orthotopic models showed a significant decrease in tumor weight following pevonedistat treatment independent of the p53 status. Novel chemotherapy agents, such as the NEDD8-activating enzyme (NAE) inhibitor pevonedistat, deserve further study in the treatment of neuroblastoma.
Levels of Circulating PD-L1 Are Decreased in Patients with Resectable Cholangiocarcinoma
Authors: Roderburg Christoph , Loosen Sven H. , Bednarsch Jan , Alizai Patrick H. , Roeth Anjali A. , Schmitz Sophia M. , Vucur Mihael , Luedde Mark , Paffenholz Pia , Tacke Frank , Trautwein Christian , Ulmer Tom F. , Neumann Ulf Peter , Luedde Tom
Published: June 2021

Tumor resection represents the only curative treatment option for patients with biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (CCA), perihilar and extrahepatic CCA and gallbladder cancer. However, many patients develop early tumor recurrence and are unlikely to benefit from surgery. Therefore, markers to identify ideal surgical candidates are urgently needed. Circulating programmed cell death 1 ligand 1 (PD-L1) has recently been associated with different malignancies, including pancreatic cancer which closely resembles BTC in terms of patients’ prognosis and tumor biology. Here, we aim at evaluating a potential role of circulating PD-L1 as a novel biomarker for resectable BTC. Methods: Serum levels of PD-L1 were analyzed by ELISA in 73 BTC patients and 42 healthy controls. Results: Circulating levels of preoperative PD-L1 were significantly lower in patients with BTC compared to controls. Patients with low PD-L1 levels displayed a strong trend towards an impaired prognosis, and circulating PD-L1 was negatively correlated with experimental markers of promalignant tumor characteristics such as CCL1, CCL21, CCL25 and CCL26. For 37 out of 73 patients, postoperative PD-L1 levels were available. Interestingly, after tumor resection, circulating PD-L1 raised to almost normal levels. Notably, patients with further decreasing PD-L1 concentrations after surgery showed a trend towards an impaired postoperative outcome. Conclusion: Circulating PD-L1 levels were decreased in patients with resectable BTC. Lack of normalization of PD-L1 levels after surgery might identify patients at high risk for tumor recurrence or adverse outcome.
Water Infrastructure Asset Management Is Evolving
Authors: Pathirana Assela , Heijer Frank den , Sayers Paul B
Published: June 2021

Infrastructure Asset Management (IAM) is the process by which decisions are made and resources allocated to ensure organisational or societal assets continue to deliver, as required. IAM is an evolving field. We discuss this evolution and present our perspectives on the future direction of IAM. IAM was born as a response to the poor state of maintenance of infrastructure, largely due to lack of resources, and emphasizes the need to prioritize maintenance and renewal using risk-based approaches. The demands on IAM have also continued to evolve as asset systems have become more complex, with multifunctionality, adaptative capacity and nature-based infrastructure, all issues that IAM must now consider. These challenges underpin the changing context of Water Infrastructure Asset Management (WIAM) and the opportunity for WIAM to harness new technical developments from other IAM domains. WIAM will need to continue to evolve, responding to these challenges and take advantage of these opportunities through research and application in collaboration with a relevant education and capacity development agenda.
Survival Associations between Patient Age and Treatment Modality in Olfactory Neuroblastoma: A Retrospective Population-Based Study
Authors: Burnham Andre J. , Burnham Phillip A. , Horwitz Edwin M.
Published: June 2021

Olfactory neuroblastoma (ONB) is a rare neuroepithelial-derived malignancy that usually presents in the nasal cavity. The rarity of ONB has led to conflicting reports regarding associations of patient age and ONB survival and outcome. Moreover, long-term outcomes of chemotherapy and other treatment modalities are speculated. Here, we aimed to compare survival outcomes across age groups through time and determine associations between treatment modality and survival. In this retrospective population-based study, we analyzed the SEER 2000–2016 Database for patients with ONB tumors. Using Kaplan–Meier survival analysis, a significant effect of age and cancer-specific survival (CSS) was observed; geriatric ONB patients had the lowest CSS overall. Generalized linear models and survival analyses demonstrated that CSS of the pediatric patient population was similar to the geriatric group through 100 months but plateaued thereafter and was the highest of all age groups. Radiation and surgery were associated with increased CSS, while chemotherapy was associated with decreased CSS. GLM results showed that tumor grade, stage and lymph node involvement had no CSS associations with age or treatment modality. Our results provide insight for future investigations of long-term outcomes associated with ONB patient age and treatment modality, and we conclude that survival statistics of ONB patients should be analyzed in terms of trends through time rather than fixed in time.
Pharmacodynamics and Outcomes of a De-Escalation Strategy with Half-Dose Prasugrel or Ticagrelor in East Asians Patients with Acute Coronary Syndrome: Results from HOPE-TAILOR Trial
Authors: Jin Cai-De , Kim Moo-Hyun , Song Kai , Jin Xuan , Lee Kwang-Min , Park Jong-Sung , Cho Young-Rak , Yun Sung-Cheol , Lee Michael S.
Published: June 2021

East Asians treated with potent P2Y12 inhibitors (prasugrel or ticagrelor) generally experience more intense platelet inhibitory responses resulting in an increased risk of major bleeding. Whether a half-dose de-escalation strategy improves the net clinical benefit in Korean patients with acute coronary syndrome (ACS) remains uncertain. A total of 120 patients were pragmatically randomized to either prasugrel (n = 39, 60 mg loading dose (LD)/10 mg maintenance dose (MD)), ticagrelor (n = 40, 180 mg LD/90 mg MD), or clopidogrel (n = 41, 600 mg LD/75 mg MD) followed by a half-dose reduction at 1 month, or conventional dose 75 mg clopidogrel. The primary endpoint was the incidence of optimal platelet reactivity (OPR), defined as a P2Y12 reaction unit (PRU) value between 85 and 208 (by VerifyNow) at 3 months. Ticagrelor treatment achieved a significantly lower PRU compared with prasugrel and clopidogrel (31.0 ± 34.5 vs. 93.2 ± 57.1 vs. 153.1 ± 69.4), resulting in the lowest rate of OPR (12.5% vs. 48.7% vs. 63.4%). At 9 months, the minor bleeding was significantly higher with potent P2Y12 inhibitors than with clopidogrel (31.6% vs. 12.2%; HR, 2.93; 95% CI, 1.12–7.75). Only a few patients experienced ischemic complications. In Korean ACS patients, a de-escalation strategy with half-dose ticagrelor and prasugrel from standard dose increased the OPR rate significantly. Half-dose ticagrelor had a lower OPR rate and greater platelet inhibition compared with half-dose prasugrel as well as conventional-dose clopidogrel. Optimal dose reduction strategies for potent P2Y12 inhibitors require further investigation to balance safety and efficacy.
Patients with Non-Obstructive Coronary Artery Disease Require Strict Control of All Cardiovascular Risk Factors: Results from the Polish Local Population Medical Records
Authors: Hiczkiewicz Jarosław , Burchardt Paweł , Budzianowski Jan , Pieszko Konrad , Hiczkiewicz Dariusz , Musielak Bogdan , Winnicka-Zielińska Anna , Keller Daria M. , Faron Wojciech , Rzeźniczak Janusz
Published: June 2021

The aim of the project was to compare patients treated with percutaneous transluminal coronary angioplasty (PTCA), who also had undergone PTCA in the past, with a group of people who had had no angiographic stenosis in the lumen of the coronary arteries in the past, and who also required PTCA during index hospitalization. The secondary aim was to compare the obtained data with the characteristics of a group of people who had undergone angiography twice and for whom no significant stenosis had been found in their coronary arteries. The study used registry data concerning 3085 people who had undergone at least two invasive procedures. Acute coronary syndrome (ACS) was significantly more often observed (Non-ST-segment elevation myocardial infarction (NSTEMI) OR 2.76 [1.91–3.99] and ST-segment elevation myocardial infarction (STEMI) OR 2.35 [1.85–2.99]) in patients with no significant coronary stenosis in the past (who required coronary angioplasty at the time of the study), compared to patients who had already had PTCA. They also demonstrated more frequent occurrence of ‘multivessel disease’. This was probably most likely caused by inadequate control of cardiovascular risk factors, as determined by higher total cholesterol levels ([mg/dL] 193.7 ± 44.4 vs. 178.2 ± 43.7) and LDL (123.4 ± 36.2 vs. 117.7 ± 36.2). On the other hand, patients in whom no significant stenosis was found in two consecutive angiographies were more likely to be burdened with chronic obstructive pulmonary disease, atrial fibrillation and chronic kidney disease.