bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards the Development of a Substance Abuse Index (SEI) through Informatics
Authors: Guttha Nikhila , Miao Zhuqi , Shamsuddin Rittika
Published: November 2021

Substance abuse or drug dependence is a prevalent phenomenon, and is on the rise in United States. Important contributing factors for the prevalence are the addictive nature of certain medicinal/prescriptive drugs, individual dispositions (biological, physiological, and psychological), and other external influences (e.g., pharmaceutical advertising campaigns). However, currently there is no comprehensive computational or machine learning framework that allows systematic studies of substance abuse and its factors with majority of the works using subjective surveys questionnaires and focusing on classification techniques. Lacking standardized methods and/or measures to prescribe medication and to study substance abuse makes it difficult to advance through collective research efforts. Thus, in this paper, we propose to test the feasibility of developing a, objective substance effect index, SEI, that can measure the tendency of an individual towards substance abuse. To that end, we combine the benefits of Electronics Medical Records (EMR) with machine learning technology by defining SEI as a function of EMR data and using logistics regression to obtain a closed form expression for SEI. We conduct various evaluations to validate the proposed model, and the results show that further work towards the development of SEI will not only provide researchers with standard computational measure for substance abuse, but may also allow them to study certain attribute interactions to gain further insights into substance abuse tendencies.
Suitability of On-Farm Green Compost for the Production of Baby Leaf Species
Authors: De Falco Enrica , Vitti Antonella , Celano Giuseppe , Ronga Domenico
Published: November 2021

This study evaluated, for the first time, the suitability of on-farm green compost (GC) from the fourth range sector for the production, in a controlled environment, of six baby leaf species (radish, lettuce, rocket, chard, sorrel and dill), characterized by short cultivation cycles. The pH and electrical conductivity of potting soil-compost mixtures were affected by the different amounts of GC added to the potting soil. Germination tests on Lactuca sativa seeds indicated no phytotoxic effects when GC was used to prepare aqueous extracts diluted at 50% and 25% (v/v). In the pot experiment, GC was used at four different dosages in the growing medium, inducing different impacts on growth parameters, depending on the species and applied dose. The greatest plant growth responses were determined by using less than 3.5 g of GC in 100 g of potting soil. Significant positive correlations between the dry weights of root and shoot (r = 0.77 **), seedling height (r = 0.51 **) and the number of true leaves number (r = 0.56 **) confirmed the close relationship between the root system biomass and the growth parameters of aboveground organs. The study highlights that on-farm green compost, used as partial growing substrate, provides a good opportunity to obtain baby leaf species with well-developed root systems.
Validity of the Friedrich Short Form of the Questionnaire on Resources and Stress in Parents of Individuals with Autism Spectrum Disorder
Authors: Park Eun-Young
Published: November 2021

There is insufficient knowledge about the psychometric properties of the Friedrich short form of the Questionnaire on Resources and Stress (QRS-F) used to measure the caregiving burden of caregivers of individuals with autism spectrum disorder (ASD). The present study, therefore, aimed to confirm the validity of the QRS-F. The data selected using the systematic sampling method were analyzed to verify the factor structure of the QRS-F on parents of individuals with ASD. Exploratory and confirmatory factor analyses were employed to confirm the validity and the factor structure of the scale. The Pearson correlation coefficient was calculated to verify the relation with other measures. The original factor model was not appropriate to assess the caregiving burden on parents of individuals with ASD because the models did not show adequate fit indices. The evaluation of results based on a total score was explored, which demonstrated the expected association between depression severity and caregiving time. Overall, this study supports the use of the QRS-F for measuring the caregiving burden of parents of individuals with ASD by comparing the total score with other related variables.
Social Norms Change and Tobacco Use: A Protocol for a Systematic Review and Meta-Analysis of Interventions
Authors: Lahiri Shaon , Bingenheimer Jeffrey B. , Evans William Douglas , Wang Yan , Dubey Priyanka , Snowden Bobbi
Published: November 2021

Tobacco use kills more than eight million individuals each year, and results in substantial economic and human capital loss across nations. While effective supply-side solutions to tobacco control exist, these approaches are less effective at promoting cessation among heavy smokers, and less feasible to implement in countries with weaker tobacco control policy environments. Thus, effective demand-side solutions are needed. Shifting social norms around tobacco use is one such promising approach. To this end, a systematic review and meta-analysis of social norms intervention studies to influence tobacco use will be conducted following PRISMA 2020 guidance. Tobacco intervention studies with at least two time points that explicitly mention social norms or social influence as part of an intervention or set of measured variables will be included. Literature sources will comprise PubMed, Scopus, PsycInfo, and the Cochrane Trial Registry, as well as several grey literature sources. Two reviewers will independently screen studies, and risk of bias will be assessed using the Cochrane Risk of Bias 2 and ROBINS-I tools. The primary outcomes will be change in tobacco use and change in social norms. A random-effects meta-analysis will be conducted for both outcomes. Sources of heterogeneity will be explored using meta-regression with key covariates. Non-reporting biases will be explored using funnel plots. PROSPERO: CRD42021251535.
Collection of Data on Sex, Sexual Orientation, and Gender Identity by U.S. Public Health Data and Monitoring Systems, 2015–2018
Authors: Kress Alissa C. , Asberry Asia , Taillepierre Julio Dicent , Johns Michelle M. , Tucker Pattie , Penman-Aguilar Ana
Published: November 2021

We aimed to assess Centers for Disease Control and Prevention (CDC) data systems on the extent of data collection on sex, sexual orientation, and gender identity as well as on age and race/ethnicity. Between March and September 2019, we searched 11 federal websites to identify CDC-supported or -led U.S. data systems active between 2015 and 2018. We searched the systems’ website, documentation, and publications for evidence of data collection on sex, sexual orientation, gender identity, age, and race/ethnicity. We categorized each system by type (disease notification, periodic prevalence survey, registry/vital record, or multiple sources). We provide descriptive statistics of characteristics of the identified systems. Most (94.1%) systems we assessed collected data on sex. All systems collected data on age, and approximately 80% collected data on race/ethnicity. Only 17.7% collected data on sexual orientation and 5.9% on gender identity. Periodic prevalence surveys were the most common system type for collecting all the variables we assessed. While most U.S. public health data and monitoring systems collect data disaggregated by sex, age, and race/ethnicity, far fewer do so for sexual orientation or gender identity. Standards and examples exist to aid efforts to collect and report these vitally important data. Additionally important is increasing accessibility and appropriately tailored dissemination of reports of these data to public health professionals and other collaborators.
Do State Comprehensive Planning Statutes Address Physical Activity?: Implications for Rural Communities
Authors: Charron Lisa M. , Milstein Chloe , Moyers Samantha I. , Abildso Christiaan G. , Chriqui Jamie F.
Published: November 2021

Less than one-quarter of U.S. adults meet physical activity (PA) recommendations, with rural residents less likely to be active than urban residents. The built environment has been identified as a potential facilitator of PA and local comprehensive plans are a foundational tool for guiding the development of the built environment. The purpose of this study was therefore to understand the current landscape of comprehensive planning state statutes related to PA and rural communities. We used primary legal research methods to identify, compile, and evaluate all 50 state comprehensive planning statutes for items related to PA and conditional mandates based on population size of local jurisdictions. The presence of population-conditional planning mandates and the inclusion of PA-related items was analyzed by state-level rurality using Fisher’s exact tests. Our analyses demonstrated that (1) broader PA-related items were addressed in state statutes more often than more specific PA-related items; (2) when PA-related items were addressed, they were most likely to be mandated, subsumed elements; (3) several PA-related items were less likely to be addressed in the most rural states and/or conditionally mandated for jurisdictions meeting minimum population requirements; and (4) only two states addressed PA directly and explicitly in their comprehensive planning statutes.
A Hybrid Convolutional Neural Network Model for Diagnosis of COVID-19 Using Chest X-ray Images
Authors: Kaur Prabhjot , Harnal Shilpi , Tiwari Rajeev , Alharithi Fahd S. , Almulihi Ahmed H. , Noya Irene Delgado , Goyal Nitin
Published: November 2021

COVID-19 declared as a pandemic that has a faster rate of infection and has impacted the lives and the country’s economy due to forced lockdowns. Its detection using RT-PCR is required long time and due to which its infection has grown exponentially. This creates havoc for the shortage of testing kits in many countries. This work has proposed a new image processing-based technique for the health care systems named “C19D-Net”, to detect “COVID-19” infection from “Chest X-Ray” (XR) images, which can help radiologists to improve their accuracy of detection COVID-19. The proposed system extracts deep learning (DL) features by applying the InceptionV4 architecture and Multiclass SVM classifier to classify and detect COVID-19 infection into four different classes. The dataset of 1900 Chest XR images has been collected from two publicly accessible databases. Images are pre-processed with proper scaling and regular feeding to the proposed model for accuracy attainments. Extensive tests are conducted with the proposed model (“C19D-Net”) and it has succeeded to achieve the highest COVID-19 detection accuracy as 96.24% for 4-classes, 95.51% for three-classes, and 98.1% for two-classes. The proposed method has outperformed well in expressions of “precision”, “accuracy”, “F1-score” and “recall” in comparison with most of the recent previously published methods. As a result, for the present situation of COVID-19, the proposed “C19D-Net” can be employed in places where test kits are in short supply, to help the radiologists to improve their accuracy of detection of COVID-19 patients through XR-Images.
Diagnostic Value of the TpTe Interval in Children with Ventricular Arrhythmias
Authors: Jaromin Joanna , Markiewicz-Łoskot Grażyna , Szydłowski Lesław , Kulawik Agnieszka
Published: November 2021

Background: The changes in the period of ventricular repolarization, i.e., QT interval, QTp (Q-Tpeak) and TpTe interval (Tpeak–Tend), make it possible to assess the electrical instability of the heart muscle, which may lead to the development of life-threatening ventricular arrhythmia. The aim of the study was to determine and evaluate the use of differences in T-wave morphology and durations of repolarization period parameters (QT, TpTe) in resting ECGs for children with ventricular arrhythmias. Methods: The retrospective analysis was made of the disease histories of 80 examined children with resting ECGs, which were admitted to the Children’s Cardiology Department. The study group consisted of 46 children aged 4 to 18 with ventricular arrhythmias and the control group consisted of 34 healthy children between 4 and 18 years of age, with no arrhythmias. Results: The duration of the TpTe interval was significantly (p < 0.001) longer in the group of children with ventricular arrhythmia with abnormal T-wave (bactrian/bifid, humid/biphasic) compared to the TpTe interval in children with ventricular arrhythmia with the normal repolarization period. The duration of the TpTe (p < 0.001), QTcB (p < 0.001) and QTcF (p < 0.001) intervals were significantly longer in the group of children with ventricular arrhythmias and with abnormal T-wave compared to the values of the TpTe, QTcB, and QTcF intervals of the control group with normal morphology of the repolarization period. Only the duration of the TpTe interval was significantly (p = 0.020) longer in the group of children with ventricular arrhythmia without clinical symptoms. Conclusions: Children with benign ventricular arrhythmias recorded on a standard ECG with prolonged TpTe and QT intervals and abnormal T-wave morphology require systematic and frequent cardiac check up with long term ECG recordings due to the possibility of future more severe ventricular arrhythmias. Further follow-up studies in even larger groups of patients are necessary to confirm the values of these repolarization parameters in clinical practice.
Flow. A Socially Responsible 3D Printed One-Handed Recorder
Authors: Esclapés Javier , Gómez Almudena , Ibañez Ana
Published: November 2021

The recorder is one of the most common instruments used during primary school in the formal education system in the EU. However, there are a percentage of students with only one functional hand. The existing one-handed recorders available for them to be able to play and perform in the same way as their peers are expensive and difficult to use. This study’s purpose is to document the development of Flow—a low cost one-handed recorder as well as the user’s assessment of the psychosocial benefits of the recorder. The methods used for fabrication were 3D modelling and additive manufacturing (AM) technology or 3D printing using the technique of stereolithography, and for the assessment of the product, the Psychosocial Impact of Assistive Devices Scale (PIADS) questionnaire was distributed to 20 primary school users. The results show that the use of resins and Stereolithography is appropriate for wind instruments providing quality and strength at a fair price. Flow also proved to have a positive impact on the users and their inclusion in school. The main conclusions of this study underscore the adequacy of using AM for adaptations required for people with disabilities and the positive psychosocial benefits generated by the use of Flow in children.
Spatio-Temporal Characteristics of SO2 across Weifang from 2008 to 2020
Authors: Zhu Lining , Zhang Yu , Wu Zheng , Zhang Chengcheng
Published: November 2021

China has achieved good results in SO2 pollution control, but SO2 pollution still exists in some areas. Analyzing the spatio-temporal distribution of SO2 is critical for regional SO2 pollution prevention and control. Compared with existing air pollution studies that paid more attention to PM2.5, NO2 and O3, and focused on the macro scale, this study took the small-scale Weifang city as the research area, analyzed the temporal and spatial changes in SO2, discussed the migration trajectory of SO2 pollution and explored the impact of wind on SO2 pollution. The results show that the average annual concentration of SO2 in Weifang has exhibited a downward trend in the past 13 years, showing the basic characteristics of “highest in winter, lowest in summer and slightly higher in spring and autumn”, “highest on Sunday, lowest on Thursday and gradually decreasing from Monday to Thursday” and “highest at 9 a.m., lowest at 4 p.m. and gradually increasing from midnight to 9 a.m.”. SO2 concentration showed obvious spatial heterogeneity: higher in the north and lower in the south. In addition, Shouguang, Changyi and Gaomi were seriously polluted. The SO2 pollution shifted from south to northeast. The clean wind direction (southeast wind and northeast wind) of Weifang city accounted for about 41%, and the pollution wind direction (northwest wind and west wind) accounted for about 7%. Drawing from the multi-scale analysis, vegetation, precipitation, temperature, transport situation and human activity were the most relevant factors. Limited to data collection, more quantitative research is needed to gain insight into the influence mechanism in the future.
Self-Reported and Device-Measured Physical Activity in Leisure Time and at Work and Associations with Cardiovascular Events—A Prospective Study of the Physical Activity Paradox
Authors: Kuster Roman P. , von Rosen Philip , Grooten Wilhelmus J. A. , Dohrn Ing-Mari , Hagströmer Maria
Published: November 2021

The beneficial health effects of physical activity, in particular moderate-to-vigorous physical activity (MVPA), are well documented, but there is an ongoing scientific debate whether the domain matters, i.e., whether leisure time physical activity is beneficial and occupational physical activity is detrimental to health, referred to as the physical activity paradox. The present study, therefore, analyzed the association between self-reported and device-measured physical activity and cardiovascular events in both domains. A representative sample of 807 individuals was followed for 14.6 ± 1.1 years, in which 59 cardiovascular events occurred. For self-reported data, Cox proportional hazard models showed no effect of physical activity in leisure and at work, while for device-measured MVPA, beneficial associations with total time spent in MVPA and occupational time spent in MVPA were found, but not for leisure time spent in MVPA. When accounting for both domains in the same model, the associations disappeared. These results indicate that it matters how physical activity is measured and that MVPA is beneficial for cardiovascular health, but the domain in which MVPA occurs does not seem to matter.
Exploring PM2.5 Environmental Efficiency and Its Influencing Factors in China
Authors: Ma Dongdong , Li Guifang , He Feng
Published: November 2021

In China, air pollution, especially fine particulate matter (PM2.5) pollution, has become increasingly serious with the rapid economic growth that has occurred over the past 40 years. This paper aims to introduce PM2.5 pollution as a constraint in the environmental efficiency research framework through the use of panel data covering the Chinese provinces from 2001–2018. PM2.5 environmental efficiency is measured with the slack-based measure (SBM)-Undesirable-variable returns-to-scale (VRS) model, and the results show that the average PM2.5 environmental efficiency score is 0.702, which indicates inefficiency, and is U-shaped over time. The PM2.5 environmental efficiency scores are unbalanced across the eight regions and 30 provinces of China. Additionally, the relationship between PM2.5 environmental efficiency and its influencing factors is examined with a tobit model, and the empirical findings indicate that the relationship between economic development and PM2.5 environmental efficiency is an inverted U, which is the opposite of the traditional environmental Kuznets curve (EKC). In addition, technological innovation, trade dependency, and regional development each have a significantly positive effect on PM2.5 environmental efficiency. However, environmental regulations, the industrial structure, and population density have significantly negative effects on PM2.5 environmental efficiency. Finally, this paper fails to prove that foreign direct investment (FDI) has created a PM2.5 “pollution haven” in China.
The Role of Gut and Lung Microbiota in Susceptibility to Tuberculosis
Authors: Comberiati Pasquale , Di Cicco Maria , Paravati Francesco , Pelosi Umberto , Di Gangi Alessandro , Arasi Stefania , Barni Simona , Caimmi Davide , Mastrorilli Carla , Licari Amelia , Chiera Fernanda
Published: November 2021

Tuberculosis is one of the most common infectious diseases and infectious causes of death worldwide. Over the last decades, significant research effort has been directed towards defining the understanding of the pathogenesis of tuberculosis to improve diagnosis and therapeutic options. Emerging scientific evidence indicates a possible role of the human microbiota in the pathophysiology of tuberculosis, response to therapy, clinical outcomes, and post-treatment outcomes. Although human studies on the role of the microbiota in tuberculosis are limited, published data in recent years, both from experimental and clinical studies, suggest that a better understanding of the gut–lung microbiome axis and microbiome–immune crosstalk could shed light on the specific pathogenetic mechanisms of Mycobacterium tuberculosis infection and identify new therapeutic targets. In this review, we address the current knowledge of the host immune responses against Mycobacterium tuberculosis infection, the emerging evidence on how gut and lung microbiota can modulate susceptibility to tuberculosis, the available studies on the possible use of probiotic–antibiotic combination therapy for the treatment of tuberculosis, and the knowledge gaps and future research priorities in this field.
Mental Health Provision in UK Secondary Schools
Authors: Garside Megan , Wright Barry , Nekooi Roshanak , Allgar Victoria
Published: November 2021

Research reports high levels of mental health problems faced by young people in the UK. Schools provide a range of mental health support services, although these are often not robustly evaluated. This paper aims to explore the mental health provision of secondary schools across two large regions in the North of England and provide comparisons to the mental health questionnaire scores of their pupils. Results are part of a wider study providing an overview of the mental health of secondary school pupils. Measures include the Strengths and Difficulties Questionnaire, distributed to year 8, 9, and 11 pupils attending secondary schools and a bespoke mental health service provision questionnaire for school staff at the same schools. A total of 6328 pupil questionnaires and 36 staff questionnaires were returned from 21 schools. Results showed a non-significant correlation between provision and young people’s mental health scores and highlight a range of factors to take into consideration. There is a need to improve the evaluation and recording of school-based mental health provision. Mental health difficulties in young people are prevalent in schools. Future research is needed to elucidate which types of services are most helpful in preventing, supporting, and signposting those with mental health problems.
Oxidative Stress and Respiratory Diseases in Preterm Newborns
Authors: Cannavò Laura , Perrone Serafina , Viola Valeria , Marseglia Lucia , Di Rosa Gabriella , Gitto Eloisa
Published: November 2021

Premature infants are exposed to increased generation of reactive oxygen species, and on the other hand, they have a deficient antioxidant defense system. Oxidative insult is a salient part of lung injury that begins as acute inflammatory injury in respiratory distress disease and then evolves into chronic and structural scarring leading to bronchopulmonary dysplasia. Oxidative stress is also involved in the pathogenesis of pulmonary hypertension in newborns through the modulation of the vascular tone and the response to pulmonary vasodilators, with consequent decrease in the density of the pulmonary vessels and thickening of the pulmonary arteriolar walls. Oxidative stress has been recognized as both a trigger and an endpoint for several events, including inflammation, hypoxia, hyperoxia, drugs, transfusions, and mechanical ventilation, with impairment of pulmonary function and prolonged lung damage. Redoxomics is the most fascinating new measure to address lung damage due to oxidative stress. The new challenge is to use omics data to discover a set of biomarkers useful in diagnosis, prognosis, and formulating optimal and individualized neonatal care. The aim of this review was to examine the most recent evidence on the relationship between oxidative stress and lung diseases in preterm newborns. What is currently known regarding oxidative stress-related lung injury pathogenesis and the available preventive and therapeutic strategies are also discussed.
Anti-Müllerian Hormone in Pathogenesis, Diagnostic and Treatment of PCOS
Authors: Rudnicka Ewa , Kunicki Michał , Calik-Ksepka Anna , Suchta Katarzyna , Duszewska Anna , Smolarczyk Katarzyna , Smolarczyk Roman
Published: November 2021

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women. It is characterized by chronic anovulation, hyperandrogenism, and the presence of polycystic ovary in ultrasound examination. PCOS is specified by an increased number of follicles at all growing stages, mainly seen in the preantral and small antral follicles and an increased serum level of Anti-Müllerian Hormone (AMH). Because of the strong correlation between circulating AMH levels and antral follicle count on ultrasound, Anti-Müllerian Hormone has been proposed as an alternative marker of ovulatory dysfunction in PCOS. However, the results from the current literature are not homogeneous, and the specific threshold of AMH in PCOS and PCOM is, therefore, very challenging. This review aims to update the current knowledge about AMH, the pathophysiology of AMH in the pathogenesis of PCOS, and the role of Anti-Müllerian Hormone in the treatment of this syndrome.
(De)stabilization of Alpha-Synuclein Fibrillary Aggregation by Charged and Uncharged Surfactants
Authors: Loureiro Joana Angélica , Andrade Stéphanie , Goderis Lies , Gomez-Gutierrez Ruben , Soto Claudio , Morales Rodrigo , Pereira Maria Carmo
Published: November 2021

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. An important hallmark of PD involves the pathological aggregation of proteins in structures known as Lewy bodies. The major component of these proteinaceous inclusions is alpha (α)-synuclein. In different conditions, α-synuclein can assume conformations rich in either α-helix or β-sheets. The mechanisms of α-synuclein misfolding, aggregation, and fibrillation remain unknown, but it is thought that β-sheet conformation of α-synuclein is responsible for its associated toxic mechanisms. To gain fundamental insights into the process of α-synuclein misfolding and aggregation, the secondary structure of this protein in the presence of charged and non-charged surfactant solutions was characterized. The selected surfactants were (anionic) sodium dodecyl sulphate (SDS), (cationic) cetyltrimethylammonium chloride (CTAC), and (uncharged) octyl β-D-glucopyranoside (OG). The effect of surfactants in α-synuclein misfolding was assessed by ultra-structural analyses, in vitro aggregation assays, and secondary structure analyses. The α-synuclein aggregation in the presence of negatively charged SDS suggests that SDS-monomer complexes stimulate the aggregation process. A reduction in the electrostatic repulsion between N- and C-terminal and in the hydrophobic interactions between the NAC (non-amyloid beta component) region and the C-terminal seems to be important to undergo aggregation. Fourier transform infrared spectroscopy (FTIR) measurements show that β-sheet structures comprise the assembly of the fibrils.
Genome-Wide Identification and Characterization of Soybean GmLOR Gene Family and Expression Analysis in Response to Abiotic Stresses
Authors: Fang Yisheng , Cao Dong , Yang Hongli , Guo Wei , Ouyang Wenqi , Chen Haifeng , Shan Zhihui , Yang Zhonglu , Chen Shuilian , Li Xia , Chen Limiao , Zhou Xinan
Published: November 2021

The LOR (LURP-one related) family genes encode proteins containing a conserved LOR domain. Several members of the LOR family genes are required for defense against Hyaloperonospora parasitica (Hpa) in Arabidopsis. However, there are few reports of LOR genes in response to abiotic stresses in plants. In this study, a genome-wide survey and expression levels in response to abiotic stresses of 36 LOR genes from Glycine max were conducted. The results indicated that the GmLOR gene family was divided into eight subgroups, distributed on 14 chromosomes. A majority of members contained three extremely conservative motifs. There were four pairs of tandem duplicated GmLORs and nineteen pairs of segmental duplicated genes identified, which led to the expansion of the number of GmLOR genes. The expansion patterns of the GmLOR family were mainly segmental duplication. A heatmap of soybean LOR family genes showed that 36 GmLOR genes exhibited various expression patterns in different tissues. The cis-acting elements in promoter regions of GmLORs include abiotic stress-responsive elements, such as dehydration-responsive elements and drought-inducible elements. Real-time quantitative PCR was used to detect the expression level of GmLOR genes, and most of them were expressed in the leaf or root except that GmLOR6 was induced by osmotic and salt stresses. Moreover, GmLOR4/10/14/19 were significantly upregulated after PEG and salt treatments, indicating important roles in the improvement of plant tolerance to abiotic stress. Overall, our study provides a foundation for future investigations of GmLOR gene functions in soybean.
Age-Related Changes in Lipidome of Rat Frontal Cortex and Cerebellum Are Partially Reversed by Methionine Restriction Applied in Old Age
Authors: Jové Mariona , Cabré Rosanna , Mota-Martorell Natàlia , Martin-Garí Meritxell , Obis Èlia , Ramos Paula , Canales Iván , Galo-Licona José Daniel , Sol Joaquim , Nogueras Lara , Torres Pascual , Portero-Otín Manuel , Ayala Victòria , Ferrer Isidro , Pamplona Reinald
Published: November 2021

Lipids are closely associated with brain structure and function. However, the potential changes in the lipidome induced by aging remain to be elucidated. In this study, we used chromatographic techniques and a mass spectrometry-based approach to evaluate age-associated changes in the lipidome of the frontal cortex and cerebellum obtained from adult male Wistar rats (8 months), aged male Wistar rats (26 months), and aged male Wistar rats submitted to a methionine restriction diet (MetR)—as an anti-aging intervention—for 8 weeks. The outcomes revealed that only small changes (about 10%) were observed in the lipidome profile in the cerebellum and frontal cortex during aging, and these changes differed, in some cases, between regions. Furthermore, a MetR diet partially reversed the effects of the aging process. Remarkably, the most affected lipid classes were ether-triacylglycerols, diacylglycerols, phosphatidylethanolamine N-methylated, plasmalogens, ceramides, and cholesterol esters. When the fatty acid profile was analyzed, we observed that the frontal cortex is highly preserved during aging and maintained under MetR, whereas in the cerebellum minor changes (increased monounsaturated and decreased polyunsaturated contents) were observed and not reversed by MetR. We conclude that the rat cerebellum and frontal cortex have efficient mechanisms to preserve the lipid profile of their cell membranes throughout their adult lifespan in order to maintain brain structure and function. A part of the small changes that take place during aging can be reversed with a MetR diet applied in old age.
Recent Findings Related to Cardiomyopathy and Genetics
Authors: Yamada Takanobu , Nomura Seitaro
Published: November 2021

With the development and advancement of next-generation sequencing (NGS), genetic analysis is becoming more accessible. High-throughput genetic studies using NGS have contributed to unraveling the association between cardiomyopathy and genetic background, as is the case with many other diseases. Rare variants have been shown to play major roles in the pathogenesis of cardiomyopathy, which was empirically recognized as a monogenic disease, and it has been elucidated that the clinical course of cardiomyopathy varies depending on the causative genes. These findings were not limited to dilated and hypertrophic cardiomyopathy; similar trends were reported one after another for peripartum cardiomyopathy (PPCM), cancer therapy-related cardiac dysfunction (CTRCD), and alcoholic cardiomyopathy (ACM). In addition, as the association between clinical phenotypes and the causative genes becomes clearer, progress is being made in elucidating the mechanisms and developing novel therapeutic agents. Recently, it has been suggested that not only rare variants but also common variants contribute to the development of cardiomyopathy. Cardiomyopathy and genetics are approaching a new era, which is summarized here in this overview.
Human Pluripotent Stem Cell-Derived Neural Progenitor Cells Promote Retinal Ganglion Cell Survival and Axon Recovery in an Optic Nerve Compression Animal Model
Authors: Park Mira , Kim Hyun-Mun , Shin Hyun-Ah , Lee Seung-Hyun , Hwang Dong-Youn , Lew Helen
Published: November 2021

Human pluripotent stem cell-derived neural progenitor cells (NPCs) have the potential to recover from nerve injury. We previously reported that human placenta-derived mesenchymal stem cells (PSCs) have neuroprotective effects. To evaluate the potential benefit of NPCs, we compared them to PSCs using R28 cells under hypoxic conditions and a rat model of optic nerve injury. NPCs and PSCs (2 × 106 cells) were injected into the subtenon space. After 1, 2, and 4 weeks, we examined changes in target proteins in the retina and optic nerve. NPCs significantly induced vascular endothelial growth factor (Vegf) compared to age-matched shams and PSC groups at 2 weeks; they also induced neurofilaments in the retina compared to the sham group at 4 weeks. In addition, the expression of brain-derived neurotrophic factor (Bdnf) was high in the retina in the NPC group at 2 weeks, while expression in the optic nerve was high in both the NPC and PSC groups. The low expression of ionized calcium-binding adapter molecule 1 (Iba1) in the retina had recovered at 2 weeks after NPC injection and at 4 weeks after PSC injection. The expression of the inflammatory protein NLR family, pyrin domain containing 3 (Nlrp3) was significantly reduced at 1 week, and that of tumor necrosis factor-α (Tnf-α) in the optic nerves of the NPC group was lower at 2 weeks. Regarding retinal ganglion cells, the expressions of Brn3a and Tuj1 in the retina were enhanced in the NPC group compared to sham controls at 4 weeks. NPC injections increased Gap43 expression from 2 weeks and reduced Iba1 expression in the optic nerves during the recovery period. In addition, R28 cells exposed to hypoxic conditions showed increased cell survival when cocultured with NPCs compared to PSCs. Both Wnt/β-catenin signaling and increased Nf-ĸb could contribute to the rescue of damaged retinal ganglion cells via upregulation of neuroprotective factors, microglial engagement, and anti-inflammatory regulation by NPCs. This study suggests that NPCs could be useful for the cellular treatment of various optic neuropathies, together with cell therapy using mesenchymal stem cells.
FOXO3a and Its Regulators in Prostate Cancer
Authors: Habrowska-Górczyńska Dominika Ewa , Kozieł Marta Justyna , Kowalska Karolina , Piastowska-Ciesielska Agnieszka Wanda
Published: November 2021

Forkhead box O3 (FOXO3a) is a member of a subfamily of forkhead transcription factors involved in the basic processes within a cell, including proliferation, apoptosis, cell cycle regulation, and DNA damage. As a transcription factor, FOXO3a is involved in the response to cellular stress, UV radiation, or oxidative stress. Its regulation is based on the modification of proteins as well as regulation by other proteins, e.g., growth factors. FOXO3a is commonly deregulated in cancer cells, and its inactivation is associated with initiation and progression of tumorigenesis, suggesting its role as a tumor suppressor; however, its role is still disputed and seems to be dependent on upstream signaling. Nevertheless, FOXO3a serves as an interesting potential target in therapies as it is regulated during treatment with very common anti-cancer drugs such as paclitaxel, cisplatin, docetaxel, and doxorubicin. This review aims to update the reported role of FOXO3a in prostate cancer (PCa), with a focus on its regulators that might serve as potential therapeutic agents in PCa therapy.
Direct Electrochemical Generation of Catalytically Competent Oxyferryl Species of Classes I and P Dye Decolorizing Peroxidases
Authors: Scocozza Magalí F. , Martins Lígia O. , Murgida Daniel H.
Published: November 2021

This work introduces a novel way to obtain catalytically competent oxyferryl species for two different dye-decolorizing peroxidases (DyPs) in the absence of H2O2 or any other peroxide by simply applying a reductive electrochemical potential under aerobic conditions. UV-vis and resonance Raman spectroscopies show that this method yields long-lived compounds II and I for the DyPs from Bacillus subtilis (BsDyP; Class I) and Pseudomonas putida (PpDyP; Class P), respectively. Both electrochemically generated high valent intermediates are able to oxidize ABTS at both acidic and alkaline pH. Interestingly, the electrocatalytic efficiencies obtained at pH 7.6 are very similar to the values recorded for regular catalytic ABTS/H2O2 assays at the optimal pH of the enzymes, ca. 3.7. These findings pave the way for the design of DyP-based electrocatalytic reactors operable in an extended pH range without the need of harmful reagents such as H2O2.
BiP Heterozigosity Aggravates Pathological Deterioration in Experimental Amyotrophic Lateral Sclerosis
Authors: Gómez-Almería Marta , Burgaz Sonia , Costas-Insua Carlos , Rodríguez-Cueto Carmen , Santos-García Irene , Rodríguez-Crespo Ignacio , García Concepción , Guzmán Manuel , de Lago Eva , Fernández-Ruiz Javier
Published: November 2021

In the present study, we investigated the involvement of the chaperone protein BiP (also known as GRP78 or Hspa5), a master regulator of intracellular proteostasis, in two mouse models of neurodegenerative diseases: amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). To this end, we used mice bearing partial genetic deletion of the BiP gene (BiP+/− mice), which, for the ALS model, were crossed with mutant SOD1 (mSOD1) transgenic mice to generate mSOD1/BiP+/− double mutant mice. Our data revealed a more intense neurological decline in the double mutants, reflected in a greater deterioration of the neurological score and rotarod performance, with also a reduced animal survival, compared to mSOD1 transgenic mice. Such worsening was associated with higher microglial (labelled with Iba-1 immunostaining) and, to a lesser extent, astroglial (labelled with GFAP immunostaining) immunoreactivities found in the double mutants, but not with a higher loss of spinal motor neurons (labelled with Nissl staining) in the spinal cord. The morphological analysis of Iba-1 and GFAP-positive cells revealed a higher presence of activated cells, characterized by elevated cell body size and shorter processes, in double mutants compared to mSOD1 mice with normal BiP expression. In the case of the PD model, BiP+/− mice were unilaterally lesioned with the parkinsonian neurotoxin 6-hydroxydopamine (6-OHDA). In this case, however, we did not detect a greater susceptibility to damage in mutant mice, as the motor defects caused by 6-OHDA in the pole test and the cylinder rearing test, as well as the losses in tyrosine hydroxylase-containing neurons and the elevated glial reactivity (labelled with CD68 and GFAP immunostaining) detected in the substantia nigra were of similar magnitude in BiP+/− mice compared with wildtype animals. Therefore, our findings support the view that a dysregulation of the protein BiP may contribute to ALS pathogenesis. As BiP has been recently related to cannabinoid type-1 (CB1) receptor function, our work also opens the door to future studies on a possible link between BiP and the neuroprotective effects of cannabinoids that have been widely reported in this neuropathological context. In support of this possibility, preliminary data indicate that CB1 receptor levels are significantly reduced in mSOD1 mice having partial deletion of BiP gene.
Aquaporin-1 Facilitates Transmesothelial Water Permeability: In Vitro and Ex Vivo Evidence and Possible Implications in Peritoneal Dialysis
Authors: Piccapane Francesca , Gerbino Andrea , Carmosino Monica , Milano Serena , Arduini Arduino , Debellis Lucantonio , Svelto Maria , Caroppo Rosa , Procino Giuseppe
Published: November 2021

We previously showed that mesothelial cells in human peritoneum express the water channel aquaporin 1 (AQP1) at the plasma membrane, suggesting that, although in a non-physiological context, it may facilitate osmotic water exchange during peritoneal dialysis (PD). According to the three-pore model that predicts the transport of water during PD, the endothelium of peritoneal capillaries is the major limiting barrier to water transport across peritoneum, assuming the functional role of the mesothelium, as a semipermeable barrier, to be negligible. We hypothesized that an intact mesothelial layer is poorly permeable to water unless AQP1 is expressed at the plasma membrane. To demonstrate that, we characterized an immortalized cell line of human mesothelium (HMC) and measured the osmotically-driven transmesothelial water flux in the absence or in the presence of AQP1. The presence of tight junctions between HMC was investigated by immunofluorescence. Bioelectrical parameters of HMC monolayers were studied by Ussing Chambers and transepithelial water transport was investigated by an electrophysiological approach based on measurements of TEA+ dilution in the apical bathing solution, through TEA+-sensitive microelectrodes. HMCs express Zo-1 and occludin at the tight junctions and a transepithelial vectorial Na+ transport. Real-time transmesothelial water flux, in response to an increase of osmolarity in the apical solution, indicated that, in the presence of AQP1, the rate of TEA+ dilution was up to four-fold higher than in its absence. Of note, we confirmed our data in isolated mouse mesentery patches, where we measured an AQP1-dependent transmesothelial osmotic water transport. These results suggest that the mesothelium may represent an additional selective barrier regulating water transport in PD through functional expression of the water channel AQP1.
How Immunosenescence and Inflammaging May Contribute to Hyperinflammatory Syndrome in COVID-19
Authors: Müller Ludmila , Di Benedetto Svetlana
Published: November 2021

Aging is characterized by the dynamic remodeling of the immune system designated “immunosenescence,” and is associated with altered hematopoiesis, thymic involution, and lifelong immune stimulation by multitudinous chronic stressors, including the cytomegalovirus (CMV). Such alterations may contribute to a lowered proportion of naïve T-cells and to reduced diversity of the T-cell repertoire. In the peripheral circulation, a shift occurs towards accumulations of T and B-cell populations with memory phenotypes, and to accumulation of putatively senescent and exhausted immune cells. The aging-related accumulations of functionally exhausted memory T lymphocytes, commonly secreting pro-inflammatory cytokines, together with mediators and factors of the innate immune system, are considered to contribute to the low-grade inflammation (inflammaging) often observed in elderly people. These senescent immune cells not only secrete inflammatory mediators, but are also able to negatively modulate their environments. In this review, we give a short summary of the ways that immunosenescence, inflammaging, and CMV infection may cause insufficient immune responses, contribute to the establishment of the hyperinflammatory syndrome and impact the severity of the coronavirus disease 2019 (COVID-19) in elderly people.
New Investigations with Lupane Type A-Ring Azepane Triterpenoids for Antimycobacterial Drug Candidate Design
Authors: Kazakova Oxana , Racoviceanu Roxana , Petrova Anastasiya , Mioc Marius , Militaru Adrian , Udrescu Lucreția , Udrescu Mihai , Voicu Adrian , Cummings Jason , Robertson Gregory , Ordway Diane J. , Slayden Richard A. , Șoica Codruța
Published: November 2021

Twenty lupane type A-ring azepano-triterpenoids were synthesized from betulin and its related derivatives and their antitubercular activity against Mycobacterium tuberculosis, mono-resistant MTB strains, and nontuberculous strains Mycobacterium abscessus and Mycobacterium avium were investigated in the framework of AToMIc (Anti-mycobacterial Target or Mechanism Identification Contract) realized by the Division of Microbiology and Infectious Diseases, NIAID, National Institute of Health. Of all the tested triterpenoids, 17 compounds showed antitubercular activity and 6 compounds were highly active on the H37Rv wild strain (with MIC 0.5 µM for compound 7), out of which 4 derivatives also emerged as highly active compounds on the three mono-resistant MTB strains. Molecular docking corroborated with a machine learning drug-drug similarity algorithm revealed that azepano-triterpenoids have a rifampicin-like antitubercular activity, with compound 7 scoring the highest as a potential M. tuberculosis RNAP potential inhibitor. FIC testing demonstrated an additive effect of compound 7 when combined with rifampin, isoniazid and ethambutol. Most compounds were highly active against M. avium with compound 14 recording the same MIC value as the control rifampicin (0.0625 µM). The antitubercular ex vivo effectiveness of the tested compounds on THP-1 infected macrophages is correlated with their increased cell permeability. The tested triterpenoids also exhibit low cytotoxicity and do not induce antibacterial resistance in MTB strains.
Enhancer RNA Profiling in Smoking and HPV Associated HNSCC Reveals Associations to Key Oncogenes
Authors: Shende Neil , Xu Jingyue , Li Wei Tse , Liu Jeffrey , Chakladar Jaideep , Brumund Kevin T. , Ongkeko Weg M.
Published: November 2021

Smoking and HPV infection are known causes for the vast majority of head and neck squamous cell carcinomas (HNSCC) due to their likelihood of causing gene dysregulation and genomic alterations. Enhancer RNAs (eRNAs) are non-coding RNAs that are known to increase nearby and target gene expression, and activity that has been suggested to be affected by genetic and epigenetic alterations. Here we sought to identify the effects of smoking and HPV status on eRNA expression in HNSCC tumors. We focused on four patient cohorts including smoking/HPV+, smoking/HPV−, non-smoking/HPV+, and non-smoking/HPV− patients. We used TCGA RNA-seq data from cancer tumors and adjacent normal tissue, extracted eRNA read counts, and correlated these to survival, clinical variables, immune infiltration, cancer pathways, and genomic alterations. We found a large number of differentially expressed eRNA in each patient cohort. We also found several dysregulated eRNA correlated to patient survival, clinical variables, immune pathways, and genomic alterations. Additionally, we were able to find dysregulated eRNA nearby seven key HNSCC-related oncogenes. For example, we found eRNA chr14:103272042–103272430 (eRNA-24036), which is located close to the TRAF3 gene to be differentially expressed and correlated with the pathologic N stage and immune cell populations. Using a separate validation dataset, we performed differential expression and immune infiltration analysis to validate our results from the TCGA data. Our findings may explain the association between eRNA expression, enhancer activity, and nearby gene dysregulation.