bluuebunny/crossref_metadata_2025 huggingface dataset:
IC-Based Neuro-Stimulation Environment for Arbitrary Waveform Generation
Authors: Kolbl Florian , Bornat Yannick , Castelli Jonathan , Regnacq Louis , N’Kaoua Gilles , Renaud Sylvie , Lewis Noëlle
Published: August 2021

Electrical stimulation of the nervous system is commonly based on biphasic stimulation waveforms, which limits its relevance for some applications, such as selective stimulation. We propose in this paper a stimulator capable of delivering arbitrary waveforms to electrodes, and suitable for non-conventional stimulation strategies. Such a system enables in vivo stimulation protocols with optimized efficacy or energy efficiency. The designed system comprises a High Voltage CMOS ASIC generating a configurable stimulating current, driven by a digital circuitry implemented on a FPGA. After fabrication, the ASIC and system were characterized and tested; they successfully generated programmable waveforms with a frequential content up to 1.2 MHz and a voltage compliance between [−17.9; +18.3] V. The system is not optimum when compared to single application stimulators, but no embedded stimulator in the literature offers an equivalent bandwidth which allows the wide range of stimulation paradigms, including high-frequency blocking stimulation. We consider that this stimulator will help test unconventional stimulation waveforms and can be used to generate proof-of-concept data before designing implantable and application-dedicated implantable stimulators.
Nexus between Economic Policy Uncertainty and Renewable Energy Consumption in BRIC Nations: The Mediating Role of Foreign Direct Investment and Financial Development
Authors: Zhang Yongliang , Qamruzzaman Md. , Karim Salma , Jahan Ishrat
Published: August 2021

In recent literature, the impact of economic policy uncertainty (EPU) on macro aspects have been investigated, but the aspect of energy, precisely renewable energy still to explore. The motivation of the study is to produce fresh evidence regarding the nexus between EPU and renewable energy consumption (REC) with the mediating role of forcing direct investment (FDI) and financial development (FD) in BRIC nations for the period 1997q1–2018q4. The study applied unit root tests following Ng-Perron and Zivot and Andrews for detecting variable’s stationary properties. The long-run cointegration was evaluated by implementing Bayer, Hanck combined the cointegration test, Bound testing approach, and tBDM test. Both linear and non-linear ARDL were implemented to evaluate long-run and short-run shocks, and directional causality was assessed through a non-granger causality test. Furthermore, the study implemented robustness by implementing fully-modified OLS, dynamic OLS, and canonical cointegrating regression (CCR). Unit root test established the variables are stationary after the first difference; moreover, the Bayer and Hanck cointegration test confirmed the long-run association between EPU, FD, FD, and REC in BRIC nations. Accruing to ARDL estimation, adverse effects running from EPU to REC both in the long run and short run. Furthermore, the positive statistically significant linkage revealed for FDI and FD to REC implies that clean energy integration could be augmented with continual inflows of FDI and development of the financial sector. Model estimation with asymmetric assumption, the study documented asymmetric effects running from EPU, FDI, and FD to renewable energy consumption, especially in the long run. Finally, the directional causality revealed unidirectional causality between REC and EPU, whereas the feedback hypothesis was disclosed for FDI and REC] and FD and REC. Study findings postulated that the role of foreign direct investment and financial development is critically significant because technological advancement and capital investment augment clean energy integration through the application of renewable energy.
A Review on Artificial Intelligence Applications for Grid-Connected Solar Photovoltaic Systems
Authors: Kurukuru Varaha Satra Bharath , Haque Ahteshamul , Khan Mohammed Ali , Sahoo Subham , Malik Azra , Blaabjerg Frede
Published: August 2021

The use of artificial intelligence (AI) is increasing in various sectors of photovoltaic (PV) systems, due to the increasing computational power, tools and data generation. The currently employed methods for various functions of the solar PV industry related to design, forecasting, control, and maintenance have been found to deliver relatively inaccurate results. Further, the use of AI to perform these tasks achieved a higher degree of accuracy and precision and is now a highly interesting topic. In this context, this paper aims to investigate how AI techniques impact the PV value chain. The investigation consists of mapping the currently available AI technologies, identifying possible future uses of AI, and also quantifying their advantages and disadvantages in regard to the conventional mechanisms.
Lyapunov-Function-Based Feedback Linearization Control Strategy of Modular Multilevel Converter–Bidirectional DC–DC Converter for Vessel Integrated Power Systems
Authors: Chen Peng , Liu Jilong , Xiao Fei , Zhu Zhichao , Huang Zhaojie
Published: August 2021

The modular multilevel converter–bidirectional DC–DC converter (MMC–BDC) has been proposed to be utilized in the vessel integrated power system to interconnect the medium voltage bus and the distributed energy storage elements. In the shipboard applications, MMC–BDC faces unbalanced sub-module power operation because of the inconsistent state-of-charge (SOC) of the energy storage elements. Researchers have investigated into the unbalanced operation principle of MMC–BDC and proposed some unbalanced operation control strategies, but these traditional strategies do not perform well in both aspects of operating range and efficiency. Therefore, this paper proposes a novel Lyapunov-function-based feedback linearization control strategy for the independent sub-module voltage control of MMC–BDC, which not only shows wide unbalanced operation range and high efficiency, but also realizes the decoupling and symmetrical control of the sub-module capacitor voltages.
Building a Common Support Framework in Differing Realities—Conditions for Renewable Energy Communities in Germany and Bulgaria
Authors: Spasova Deyana , Braungardt Sibylle
Published: August 2021

The revised EU Renewable Energy Directive first introduced renewable energy communities into the EU policy framework and requires Member States to implement a support framework for them. Given the broad scientific evidence showing the benefits of community energy for a just energy transition, a successful implementation across all Member States is essential. However, the preconditions for developing support frameworks differ largely between EU nations, as some countries have long-term experiences with supporting renewable energy communities (i.e., Germany and Denmark), while in other Member States, renewable energy communities are notably non-existent (i.e., Eastern European nations). With the purpose of providing scientific evidence to support the development of a policy framework for renewable energy communities in Eastern European Member States, this article compares key factors for the development of such communities in Bulgaria and Germany, combining a literature review with expert interviews to collect primary information on Bulgaria. A country analysis puts these factors into the contexts of both countries, while a cross-country comparison demonstrates that there are significant gaps in the support framework of Bulgaria, although these gaps are, to a lesser extent, also present in Germany. We discuss these shortcomings, derive policy recommendations and identify further research needs.
Almond By-Products: Valorization for Sustainability and Competitiveness of the Industry
Authors: Barral-Martinez Marta , Fraga-Corral Maria , Garcia-Perez Pascual , Simal-Gandara Jesus , Prieto Miguel A.
Published: August 2021

The search for waste minimization and the valorization of by-products are key practices for good management and improved sustainability in the food industry. The production of almonds generates a large amount of waste, most of which is not used. Until now, almonds have been used for their high nutritional value as food, especially almond meat. The other remaining parts (skin, shell, hulls, etc.) are still little explored, even though they have been used as fuel by burning or as livestock feed. However, interest in these by-products has been increasing as they possess beneficial properties (caused mainly by polyphenols and unsaturated fatty acids) and can be used as new ingredients for the food, cosmetic, and pharmaceutical industries. Therefore, it is important to explore almond’s valorization of by-products for the development of new added-value products that would contribute to the reduction of environmental impact and an improvement in the sustainability and competitiveness of the almond industry.
Optimising Medication Use along Dementia Progression: Recommendations from a Qualitative Study
Authors: Alsaeed Dalal , Orlu Mine , Smith Felicity
Published: August 2021

Medicines management is known to be an integral part of the role of family caregivers; it also contributes to the burden and stress of caregivers’ experience. As dementia progresses, new challenges arise as a consequence, which negatively affects the ability of people living with dementia (PLWD) regarding practical decision making and may lead to a change of setting. The aim of this study is to identify and explore changes in medicines management and associated caregiver burden as dementia progresses. To examine medicines management and related issues across severities, a qualitative approach utilising face-to-face and telephone interviews with PLWD and their family caregivers in both the community and care-home setting in London was used. Follow-up interviews with family caregivers were also conducted to gain additional insight into change over time. Eleven family caregivers, ten PLWD, and eight care-home staff were interviewed in 2016. Findings identified how key changes along dementia progression affect medication use. These include changes to caregiver burden, respecting the PLWD’s autonomy and decline in capacity, scheduling and administration, choice of formulation, interactions with and between providers, and information needs. The findings assist in informing recommendations to optimise medication use and alleviate caregiver burden.
ME/CFS: Past, Present and Future
Authors: Weir William , Speight Nigel
Published: August 2021

This review raises a number of compelling issues related to the condition of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Some historical perspective is necessary in order to highlight the nature of the controversy concerning its causation. Throughout history, a pattern tends to repeat itself when natural phenomena require explanation. Dogma usually arrives first, then it is eventually replaced by scientific understanding. The same pattern is unfolding in relation to ME/CFS, but supporters of the psychological dogma surrounding its causation remain stubbornly resistant, even in the face of compelling scientific evidence to the contrary. Acceptance of the latter is not just an academic issue; the route to proper understanding and treatment of ME/CFS is through further scientific research rather than psychological theorisation. Only then will a long-suffering patient group benefit.
Waste Disposal Practices in Low-Income Settlements of South Africa
Authors: Haywood Lorren Kirsty , Kapwata Thandi , Oelofse Suzan , Breetzke Gregory , Wright Caradee Yael
Published: August 2021

Domestic solid waste is rapidly increasing due to accelerated population growth and urbanization. Improper waste disposal poses potential health risks and environmental concerns. Here, we investigated waste disposal practices in relation to household/dwelling characteristics in South African low-income communities. Data for 2014 to 2019 from a community-orientated primary care program were analyzed using logistic regression. Families who reported living in a shack were more likely to dump waste in the street. Households who reported using non-electric sources of fuel for heating/cooking, those who lacked proper sanitation, and those who did not have access to piped water inside the dwelling were more likely to dispose of waste by dumping it in the street/in the yard or burying it. Families living in low-income settlements are at risk of solid waste exposure and this situation is exacerbated by poor access to piped water, proper sanitation, and electricity.
Endometriosis—A Multifaceted Problem of a Modern Woman
Authors: Mińko Alicja , Turoń-Skrzypińska Agnieszka , Rył Aleksandra , Bargiel Patrycja , Hilicka Zuzanna , Michalczyk Kaja , Łukowska Paulina , Rotter Iwona , Cymbaluk-Płoska Aneta
Published: August 2021

Endometriosis is a chronic disease of unclear aetiology that affects millions of women around the world. It causes chronic pain, dysmenorrhea, and infertility, which significantly reduces the quality of daily life. The aim of the following study was a multivariate analysis of the functioning of women diagnosed with endometriosis, and the identification of the relationship between the level of physical activity and sexual functioning, ability to cope with stress, and the degree of anxiety and mood disorders. The prospective survey was conducted of 957 women. The research was carried out using standardised IPAQ, FSFI, HADS, and Mini-Cope questionnaires. The study showed that patients with endometriosis exhibit a higher level of depression and anxiety disorders (p = 0.01) and a lower level of sexual functions (p < 0.001). The influence of physical activity on the functioning of patients with endometriosis was demonstrated. Depending on the clinical stage of endometriosis, the influence of physical activity on individual aspects of life differed. Physical activity was shown, inter alia, to reduce anxiety (p = 0.015), and influence stress-coping strategies. Endometriosis affects the mental and physical health of women. Physical activity can reduce the severity of endometriosis symptoms and improve the daily functioning of patients.
Association of Self-Reported Physical Fitness during Late Pregnancy with Birth Outcomes and Oxytocin Administration during Labour—The GESTAFIT Project
Authors: Baena-García Laura , Marín-Jiménez Nuria , Romero-Gallardo Lidia , Borges-Cosic Milkana , Ocón-Hernández Olga , Flor-Alemany Marta , Aparicio Virginia A.
Published: August 2021

We explored (a) the associations between self-reported maternal physical fitness and birth outcomes; (b) whether self-reported maternal physical fitness (PF) is related to the administration of oxytocin to induce or stimulate labour. Pregnant women from the GESTAFIT project randomized controlled trial (n = 117) participated in this prospective longitudinal study. Maternal physical fitness was assessed through the International Fitness Scale at the 34th gestational week. Maternal and neonatal birth outcomes and oxytocin administration were collected from the obstetric medical records. Umbilical arterial and venous cord blood gas were analysed immediately after birth. Self-reported overall fitness, cardiorespiratory fitness, muscular strength and flexibility were not related to any maternal and neonatal birth outcomes (all p > 0.05). Greater speed-agility was associated with a more alkaline arterial (p = 0.04) and venous (p = 0.02) pH in the umbilical cord blood. Women who were administered oxytocin to induce or stimulate labour reported lower cardiorespiratory fitness (p = 0.013, Cohen’s d = 0.55; 95% confidence interval (CI): 0.14, 0.93) and flexibility (p = 0.040, Cohen´s d = 0.51; 95% CI: 0.09, 0.89) compared to women who were not administered oxytocin. Greater maternal physical fitness during pregnancy could be associated with better neonatal birth outcomes and lower risk of needing oxytocin administration.
Safely Managed On-Site Sanitation: A National Assessment of Sanitation Services and Potential Fecal Exposure in Indonesia
Authors: Odagiri Mitsunori , Thomas Ann , Listyasari Maraita , Mills Freya , Bain Robert E. S. , Muhammad Zainal , Slaymaker Tom , Mardikanto Aldy , Gultom Anita , Indiyani Asri , Rangkuti Hasnani , Willetts Juliet
Published: August 2021

Sustainable Development Goal target 6.2 calls for universal access to adequate and equitable sanitation, setting a more ambitious standard for ‘safely managed sanitation services’. On-site sanitation systems (e.g., septic tanks) are widely used in low- and middle-income countries (LMICs). However, the lack of indicators for assessing fecal exposure risks presents a barrier to monitoring safely managed services. Furthermore, geographic diversity and frequency of disasters require a more nuanced approach to risk-informed decision-making. Taking Indonesia as an example, the purpose of this paper is to provide insights into current status and practices for on-site sanitation services in the contexts of LMICs. Using a dataset from a national socio-economic survey (n = 295,155) coupled with village census (n = 83,931), we assessed (1) household sanitation practices across Indonesia stratified by city-level population density and meteorological factors, (2) factors associated with septic tank emptying practice, and (3) inequalities in potential fecal exposure as measured by population density and WASH access by wealth quintile. We found a high reliance on on-site sanitation facilities (80.0%), almost half of which are assumed to be ‘uncontained’ septic tanks and one in ten facilities discharging untreated waste directly into the environment. The most densely populated areas had the highest rates of septic tank emptying, though emptying rates were just 17.0%, while in the lowest population density group, emptying was rarely reported. Multivariate regression analysis demonstrated an association between flooding and drought occurrence and septic tank emptying practice. Higher groundwater usage for drinking among poorer households suggests unsafe sanitation may disproportionally affect the poor. Our study underscores the urgent need to strengthen the monitoring of on-site sanitation in LMICs by developing contextualized standards. Furthermore, the inequalities in potential fecal exposure require greater attention and tailored support mechanisms to ensure the poorest gain access to safely managed sanitation services.
Biopsychosocial Factors during the Perinatal Period: Risks, Preventative Factors, and Implications for Healthcare Professionals
Authors: Blount Ashley J. , Adams Charmayne R. , Anderson-Berry Ann L. , Hanson Corrine , Schneider Kara , Pendyala Gurudutt
Published: August 2021

Women face risks to their wellbeing during the perinatal period of pregnancy. However, there is a dearth of information on perinatal risk factors within the biopsychosocial paradigm. Emphasis is often placed on biological components associated with pregnancy and women’s health. However, psychological and social determinants of health are integral during the perinatal period, and mental wellness is often a determinant for positive maternal and neonatal health outcomes. This article reviews risk factors of perinatal wellness (e.g., physical and nutritional concerns, trauma, discrimination, adverse childhood events) and highlights protective factors for women in their perinatal period. Healthcare professionals can support perinatal health by focusing on culturally and contextually appropriate research and prevention, providing equal access to sexual and reproductive healthcare information and services, providing quality education and training for helping professionals, and supporting policies for positive sexual and reproductive women’s healthcare.
Stigma and Endometriosis: A Brief Overview and Recommendations to Improve Psychosocial Well-Being and Diagnostic Delay
Authors: Sims Omar T. , Gupta Jhumka , Missmer Stacey A. , Aninye Irene O.
Published: August 2021

Endometriosis is a chronic gynecological disease that affects approximately 1 in 10 women of reproductive age. Symptoms of severe pelvic pain, infertility, fatigue, and abnormal menstruation can cause significant negative effects on an individual’s physical and mental health, including interactions with their family, friends, and health care providers. Stigma associated with endometriosis has been under-studied and is rarely discussed in current literature. Herein, this paper aims to provide a brief overview of published literature to explore and establish the plausibility of stigma as a driver of suboptimal psychosocial well-being and diagnostic delay among individuals living with endometriosis. We present the clinical characteristics and physical and mental health consequences associated with endometriosis, highlight several theoretical constructs of stigma, and review the limited studies documenting women’s lived experiences of endometriosis-related stigma. To mitigate harmful effects of this phenomenon, we recommend increasing efforts to assess the prevalence of and to characterize endometriosis-related stigma, implementing awareness campaigns, and developing interventions that combat the multidimensional negative effects of stigma on timely care, treatment, and quality of life for individuals living with endometriosis.
Mouthwash Use and the Risk of Oral, Pharyngeal, and Laryngeal Cancer. A Meta-Analysis
Authors: Hostiuc Sorin , Ionescu Ioana Victoria , Drima Eduard
Published: August 2021

Objective: The main aim of this study was to test whether the use of mouthwash is associated with subtypes of squamous cell carcinoma of the head and neck (SCCHN) and to test the potential risk of SCCHN depending on the mouthwash use duration, frequency, or alcoholic content. Materials and methods: We performed a meta-analysis using Web of Science and Scopus databases to detect the risk change associated with mouthwash use depending on the alcohol content, duration and frequency of use, and anatomical location. We used a random-effects model with the Sidik–Jonkman estimator for effect size model measures. Results: We included 17 studies in the meta-analysis containing 17,085 cases and 20,032 controls. The risk difference for SCCHN between mouthwash users and non-users was minimal, with a value of −0.02 [−0.05, 0.01]. Alcoholic mouthwash use was associated with a minimal decrease in risk (of −0.01 [−0.07, 0.05]). Frequent usage of mouthwash was associated with a statistically significant risk increase for SCCHN but the risk increase was marginal (0.04, [0.01, 0.06]). Conclusions: Overall, our study failed to show a statistically significant correlation between mouthwash use and the risk of SCCHN. The only statistically significant correlation that we could identify was between frequent usage and SCCHN, potentially caused by prolonged contact between some constituents of mouthwash (possibly alcohol) and the oral epithelium.
Musculoskeletal Disorders’ Classification Proposal for Application in Occupational Medicine
Authors: Pereira Pablo Monteiro , Amaro João , Ribeiro Bruno Tillmann , Gomes Ana , De Oliveira Paulo , Duarte Joana , Ferraz João , Baptista João Santos , Costa José Torres
Published: August 2021

Occupational-specific classifications of musculoskeletal disorders (MSD) are scarce and do not answer specific clinical questions. Thus, a specific classification was developed and proposed, covering criteria applicable to daily clinical activity. It was considered that the disorder development process is the same across all work-related MSDs (WRMSDs). Concepts of clinical pathology were applied to the characteristics of WRMSDs pathophysiology, cellular and tissue alterations. Then, the correlation of the inflammatory mechanisms with the injury onset mode was graded into four levels (MSDs 0–3). Criteria of legal, occupational and internal medicine, semiology, physiology and orthopaedics, image medicine and diagnostics were applied. Next, the classification was analysed by experts, two occupational physicians, two physiatrists and occupational physicians and one orthopaedist. This approach will allow WRMSD prevention and improve therapeutic management, preventing injuries from becoming chronic and facilitating communication between occupational health physicians and the other specialities. The four levels tool relate aetiopathogenic, clinical, occupational and radiological concepts into a single classification. This allows for improving the ability to determine a WRMSD and understanding what preventive and therapeutic measures should be taken, avoiding chronicity. The developed tool is straightforward, easy to understand and suitable for WRMSDs, facilitating communication between occupational physicians and physicians from other specialities.
Neural and Hormonal Basis of Opposite-Sex Preference by Chemosensory Signals
Authors: Kondo Yasuhiko , Hayashi Himeka
Published: August 2021

In mammalian reproduction, sexually active males seek female conspecifics, while estrous females try to approach males. This sex-specific response tendency is called sexual preference. In small rodents, sexual preference cues are mainly chemosensory signals, including pheromones. In this article, we review the physiological mechanisms involved in sexual preference for opposite-sex chemosensory signals in well-studied laboratory rodents, mice, rats, and hamsters of both sexes, especially an overview of peripheral sensory receptors, and hormonal and central regulation. In the hormonal regulation section, we discuss potential rodent brain bisexuality, as it includes neural substrates controlling both masculine and feminine sexual preferences, i.e., masculine preference for female odors and the opposite. In the central regulation section, we show the substantial circuit regulating sexual preference and also the influence of sexual experience that innate attractants activate in the brain reward system to establish the learned attractant. Finally, we review the regulation of sexual preference by neuropeptides, oxytocin, vasopressin, and kisspeptin. Through this review, we clarified the contradictions and deficiencies in our current knowledge on the neuroendocrine regulation of sexual preference and sought to present problems requiring further study.
Nucleobindin-2/Nesfatin-1—A New Cancer Related Molecule?
Authors: Kmiecik Alicja M. , Dzięgiel Piotr , Podhorska-Okołów Marzenna
Published: August 2021

Cancer is a heterogeneous disease, and even tumors with similar clinicopathological characteristics show different biology, behavior, and treatment responses. As a result, there is an urgent need to define new prognostic and predictive markers to make treatment options more personalized. According to the latest findings, nucleobindin-2/nesfatin-1 (NUCB2/NESF-1) is an important factor in cancer development and progression. Nucleobindin-2 is a precursor protein of nesfatin-1. As NUCB2 and nesfatin-1 are colocalized in each tissue, their expression is often analyzed together as NUCB2. The metabolic function of NUCB2/NESF-1 is related to food intake, glucose metabolism, and the regulation of immune, cardiovascular and endocrine systems. Recently, it has been demonstrated that high expression of NUCB2/NESF-1 is associated with poor outcomes and promotes cell proliferation, migration, and invasion in, e.g., breast, colon, prostate, endometrial, thyroid, bladder cancers, or glioblastoma. Interestingly, nesfatin-1 is also considered an inhibitor of the proliferation of human adrenocortical carcinoma and ovarian epithelial carcinoma cells. These conflicting results make NUCB2/NESF-1 an interesting target of study in the context of cancer progression. The present review is the first to describe NUCB2/NESF-1 as a new prognostic and predictive marker in cancers.
Liver-Specific Overexpression of Prostasin Attenuates High-Fat Diet-Induced Metabolic Dysregulation in Mice
Authors: Sekine Tetsuo , Takizawa Soichi , Uchimura Kohei , Miyazaki Asako , Tsuchiya Kyoichiro
Published: August 2021

The liver has a most indispensable role in glucose and lipid metabolism where we see some of the most serious worldwide health problems. The serine protease prostasin (PRSS8) cleaves toll-like receptor 4 (TLR4) and regulates hepatic insulin sensitivity under PRSS8 knockout condition. However, liver substrate proteins of PRSS8 other than TLR4 and the effect to glucose and lipid metabolism remain unclarified with hepatic elevation of PRSS8 expression. Here we show that high-fat-diet-fed liver-specific PRSS8 transgenic mice improved glucose tolerance and hepatic steatosis independent of body weight. PRSS8 amplified extracellular signal-regulated kinase phosphorylation associated with matrix metalloproteinase 14 activation in vivo and in vitro. Moreover, in humans, serum PRSS8 levels reduced more in type 2 diabetes mellitus (T2DM) patients than healthy controls and were lower in T2DM patients with increased maximum carotid artery intima media thickness (>1.1 mm). These results identify the regulatory mechanisms of PRSS8 overexpression over glucose and lipid metabolism, as well as excessive hepatic fat storage.
Comparative Molecular Dynamics Investigation of the Electromotile Hearing Protein Prestin
Authors: Abrusci Gianfranco , Tarenzi Thomas , Sturlese Mattia , Giachin Gabriele , Battistutta Roberto , Lattanzi Gianluca
Published: August 2021

The mammalian protein prestin is expressed in the lateral membrane wall of the cochlear hair outer cells and is responsible for the electromotile response of the basolateral membrane, following hyperpolarisation or depolarisation of the cells. Its impairment marks the onset of severe diseases, like non-syndromic deafness. Several studies have pointed out possible key roles of residues located in the Transmembrane Domain (TMD) that differentiate mammalian prestins as incomplete transporters from the other proteins belonging to the same solute-carrier (SLC) superfamily, which are classified as complete transporters. Here, we exploit the homology of a prototypical incomplete transporter (rat prestin, rPres) and a complete transporter (zebrafish prestin, zPres) with target structures in the outward open and inward open conformations. The resulting models are then embedded in a model membrane and investigated via a rigorous molecular dynamics simulation protocol. The resulting trajectories are analyzed to obtain quantitative descriptors of the equilibration phase and to assess a structural comparison between proteins in different states, and between different proteins in the same state. Our study clearly identifies a network of key residues at the interface between the gate and the core domains of prestin that might be responsible for the conformational change observed in complete transporters and hindered in incomplete transporters. In addition, we study the pathway of Cl− ions in the presence of an applied electric field towards their putative binding site in the gate domain. Based on our simulations, we propose a tilt and shift mechanism of the helices surrounding the ion binding cavity as the working principle of the reported conformational changes in complete transporters.
Lipid-Based Nanosystems as a Tool to Overcome Skin Barrier
Authors: Sguizzato Maddalena , Esposito Elisabetta , Cortesi Rita
Published: August 2021

Skin may be affected by many disorders that can be treated by topical applications of drugs on the action site. With the advent of nanotechnologies, new efficient delivery systems have been developed. Particularly, lipid-based nanosystems such as liposomes, ethosomes, transferosomes, solid lipid nanoparticles, nanostructured lipid carriers, cubosomes, and monoolein aqueous dispersions have been proposed for cutaneous application, reaching in some cases the market or clinical trials. This review aims to provide an overview of the different lipid-based nanosystems, focusing on their use for topical application. Particularly, biocompatible nanosystems able to dissolve lipophilic compounds and to control the release of carried drug, possibly reducing side effects, are described. Notably, the rationale to topically administer antioxidant molecules by lipid nanocarriers is described. Indeed, the structural similarity between the nanosystem lipid matrix and the skin lipids allows the achievement of a transdermal effect. Surely, more research is required to better understand the mechanism of interaction between lipid-based nanosystems and skin. However, this attempt to summarize and highlight the possibilities offered by lipid-based nanosystems could help the scientific community to take advantage of the benefits derived from this kind of nanosystem.
Effect of Washing Treatment on the Textural Properties and Bioactivity of Silica/Chitosan/TCP Xerogels for Bone Regeneration
Authors: Pérez-Moreno Antonio , Reyes-Peces María Virtudes , Vilches-Pérez José Ignacio , Fernández-Montesinos Rafael , Pinaglia-Tobaruela Gonzalo , Salido Mercedes , de la Rosa-Fox Nicolás , Piñero Manuel
Published: August 2021

Silica/biopolymer hydrogel-based materials constitute very attractive platforms for various emerging biomedical applications, particularly for bone repair. The incorporation of calcium phosphates in the hybrid network allows for designing implants with interesting biological properties. Here, we introduce a synthesis procedure for obtaining silica–chitosan (CS)–tricalcium phosphate (TCP) xerogels, with CS nominal content varying from 4 to 40 wt.% and 10 to 20 wt.% TCP. Samples were obtained using the sol-gel process assisted with ultrasound probe, and the influence of ethanol or water as washing solvents on surface area, micro- and mesopore volume, and average pore size were examined in order to optimize their textural properties. Three washing solutions with different soaking conditions were tested: 1 or 7 days in absolute ethanol and 30 days in distilled water, resulting in E1, E7, and W30 washing series, respectively. Soaked samples were eventually dried by evaporative drying at air ambient pressure, and the formation of interpenetrated hybrid structures was suggested by Fourier transformed infrared (FTIR) spectroscopy. In addition the impact that both washing solvent and TCP content have on the biodegradation, in vitro bioactivity and osteoconduction of xerogels were explored. It was found that calcium and phosphate-containing ethanol-washed xerogels presented in vitro release of calcium (2–12 mg/L) and silicon ions (~60–75 mg/L) after one week of soaking in phosphate-buffered saline (PBS), as revealed by inductive coupled plasma (ICP) spectroscopy analysis. However, only the release of silicon was detected for water-washed samples. Besides, all the samples exhibited in vitro bioactivity in simulated body fluid (SBF), as well as enhanced in vitro cell growth and also significant focal adhesion development and maturation.
Tackling Dysfunction of Mitochondrial Bioenergetics in the Brain
Authors: Zanfardino Paola , Doccini Stefano , Santorelli Filippo M. , Petruzzella Vittoria
Published: August 2021

Oxidative phosphorylation (OxPhos) is the basic function of mitochondria, although the landscape of mitochondrial functions is continuously growing to include more aspects of cellular homeostasis. Thanks to the application of -omics technologies to the study of the OxPhos system, novel features emerge from the cataloging of novel proteins as mitochondrial thus adding details to the mitochondrial proteome and defining novel metabolic cellular interrelations, especially in the human brain. We focussed on the diversity of bioenergetics demand and different aspects of mitochondrial structure, functions, and dysfunction in the brain. Definition such as ‘mitoexome’, ‘mitoproteome’ and ‘mitointeractome’ have entered the field of ‘mitochondrial medicine’. In this context, we reviewed several genetic defects that hamper the last step of aerobic metabolism, mostly involving the nervous tissue as one of the most prominent energy-dependent tissues and, as consequence, as a primary target of mitochondrial dysfunction. The dual genetic origin of the OxPhos complexes is one of the reasons for the complexity of the genotype-phenotype correlation when facing human diseases associated with mitochondrial defects. Such complexity clinically manifests with extremely heterogeneous symptoms, ranging from organ-specific to multisystemic dysfunction with different clinical courses. Finally, we briefly discuss the future directions of the multi-omics study of human brain disorders.
The Roles of CCCH Zinc-Finger Proteins in Plant Abiotic Stress Tolerance
Authors: Han Guoliang , Qiao Ziqi , Li Yuxia , Wang Chengfeng , Wang Baoshan
Published: August 2021

Zinc-finger proteins, a superfamily of proteins with a typical structural domain that coordinates a zinc ion and binds nucleic acids, participate in the regulation of growth, development, and stress adaptation in plants. Most zinc fingers are C2H2-type or CCCC-type, named after the configuration of cysteine (C) and histidine (H); the less-common CCCH zinc-finger proteins are important in the regulation of plant stress responses. In this review, we introduce the domain structures, classification, and subcellular localization of CCCH zinc-finger proteins in plants and discuss their functions in transcriptional and post-transcriptional regulation via interactions with DNA, RNA, and other proteins. We describe the functions of CCCH zinc-finger proteins in plant development and tolerance to abiotic stresses such as salt, drought, flooding, cold temperatures and oxidative stress. Finally, we summarize the signal transduction pathways and regulatory networks of CCCH zinc-finger proteins in their responses to abiotic stress. CCCH zinc-finger proteins regulate the adaptation of plants to abiotic stress in various ways, but the specific molecular mechanisms need to be further explored, along with other mechanisms such as cytoplasm-to-nucleus shuttling and post-transcriptional regulation. Unraveling the molecular mechanisms by which CCCH zinc-finger proteins improve stress tolerance will facilitate the breeding and genetic engineering of crops with improved traits.
Cannabinoids Drugs and Oral Health—From Recreational Side-Effects to Medicinal Purposes: A Systematic Review
Authors: Bellocchio Luigi , Inchingolo Alessio Danilo , Inchingolo Angelo Michele , Lorusso Felice , Malcangi Giuseppina , Santacroce Luigi , Scarano Antonio , Bordea Ioana Roxana , Hazballa Denisa , D’Oria Maria Teresa , Isacco Ciro Gargiulo , Nucci Ludovica , Serpico Rosario , Tartaglia Gianluca Martino , Giovanniello Delia , Contaldo Maria , Farronato Marco , Dipalma Gianna , Inchingolo Francesco
Published: August 2021

Background: marijuana, the common name for cannabis sativa preparations, is one of the most consumed drug all over the world, both at therapeutical and recreational levels. With the legalization of medical uses of cannabis in many countries, and even its recreational use in most of these, the prevalence of marijuana use has markedly risen over the last decade. At the same time, there is also a higher prevalence in the health concerns related to cannabis use and abuse. Thus, it is mandatory for oral healthcare operators to know and deal with the consequences and effects of cannabis use on oral cavity health. This review will briefly summarize the components of cannabis and the endocannabinoid system, as well as the cellular and molecular mechanisms of biological cannabis action in human cells and biologic activities on tissues. We will also look into oropharyngeal tissue expression of cannabinoid receptors, together with a putative association of cannabis to several oral diseases. Therefore, this review will elaborate the basic biology and physiology of cannabinoids in human oral tissues with the aim of providing a better comprehension of the effects of its use and abuse on oral health, in order to include cannabinoid usage into dental patient health records as well as good medicinal practice. Methods: the paper selection was performed by PubMed/Medline and EMBASE electronic databases, and reported according to the PRISMA guidelines. The scientific products were included for qualitative analysis. Results: the paper search screened a total of 276 papers. After the initial screening and the eligibility assessment, a total of 32 articles were considered for the qualitative analysis. Conclusions: today, cannabis consumption has been correlated to a higher risk of gingival and periodontal disease, oral infection and cancer of the oral cavity, while the physico-chemical activity has not been completely clarified. Further investigations are necessary to evaluate a therapeutic efficacy of this class of drugs for the promising treatment of several different diseases of the salivary glands and oral diseases.
A Novel Germline Mutation of ADA2 Gene in Two “Discordant” Homozygous Female Twins Affected by Adenosine Deaminase 2 Deficiency: Description of the Bone-Related Phenotype
Authors: Vai Silvia , Marin Erika , Cosso Roberta , Saettini Francesco , Bonanomi Sonia , Cattoni Alessandro , Chiodini Iacopo , Persani Luca , Falchetti Alberto
Published: August 2021

Adenosine Deaminase 2 Deficiency (DADA2) syndrome is a rare monogenic disorder prevalently linked to recessive inherited loss of function mutations in the ADA2/CECR1 gene. It consists of an immune systemic disease including autoinflammatory vasculopathies, with a frequent onset at infancy/early childhood age. DADA2 syndrome encompasses pleiotropic manifestations such as stroke, systemic vasculitis, hematologic alterations, and immunodeficiency. Although skeletal abnormalities have been reported in patients with this disease, clear information about skeletal health, with appropriate biochemical-clinical characterization/management, its evolution over time and any appropriate clinical management is still insufficient. In this paper, after a general introduction shortly reviewing the pathophysiology of Ada2 enzymatic protein, its potential role in bone health, we describe a case study of two 27 year-old DADA2 monozygotic female twins exhibiting bone mineral density and bone turnover rate abnormalities over the years of their clinical follow-up.
Dual Nature of Relationship between Mycobacteria and Cancer
Authors: Fol Marek , Koziński Piotr , Kulesza Jakub , Białecki Piotr , Druszczyńska Magdalena
Published: August 2021

Although the therapeutic effect of mycobacteria as antitumor agents has been known for decades, recent epidemiological and experimental studies have revealed that mycobacterium-related chronic inflammation may be a possible mechanism of cancer pathogenesis. Mycobacterium tuberculosis and non-tuberculous Mycobacterium avium complex infections have been implicated as potentially contributing to the etiology of lung cancer, whereas Mycobacterium ulcerans has been correlated with skin carcinogenesis. The risk of tumor development with chronic mycobacterial infections is thought to be a result of many host effector mechanisms acting at different stages of oncogenesis. In this paper, we focus on the nature of the relationship between mycobacteria and cancer, describing the clinical significance of mycobacteria-based cancer therapy as well as epidemiological evidence on the contribution of chronic mycobacterial infections to the increased lung cancer risk.
alfaNET: A Database of Alfalfa-Bacterial Stem Blight Protein–Protein Interactions Revealing the Molecular Features of the Disease-causing Bacteria
Authors: Kataria Raghav , Kaundal Rakesh
Published: August 2021

Alfalfa has emerged as one of the most important forage crops, owing to its wide adaptation and high biomass production worldwide. In the last decade, the emergence of bacterial stem blight (caused by Pseudomonas syringae pv. syringae ALF3) in alfalfa has caused around 50% yield losses in the United States. Studies are being conducted to decipher the roles of the key genes and pathways regulating the disease, but due to the sparse knowledge about the infection mechanisms of Pseudomonas, the development of resistant cultivars is hampered. The database alfaNET is an attempt to assist researchers by providing comprehensive Pseudomonas proteome annotations, as well as a host–pathogen interactome tool, which predicts the interactions between host and pathogen based on orthology. alfaNET is a user-friendly and efficient tool and includes other features such as subcellular localization annotations of pathogen proteins, gene ontology (GO) annotations, network visualization, and effector protein prediction. Users can also browse and search the database using particular keywords or proteins with a specific length. Additionally, the BLAST search tool enables the user to perform a homology sequence search against the alfalfa and Pseudomonas proteomes. With the successful implementation of these attributes, alfaNET will be a beneficial resource to the research community engaged in implementing molecular strategies to mitigate the disease. alfaNET is freely available for public use at http://bioinfo.usu.edu/alfanet/.
Purinergic Signalling in Allogeneic Haematopoietic Stem Cell Transplantation and Graft-versus-Host Disease
Authors: Cuthbertson Peter , Geraghty Nicholas J. , Adhikary Sam R. , Bird Katrina M. , Fuller Stephen J. , Watson Debbie , Sluyter Ronald
Published: August 2021

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for blood cancers and other haematological disorders. However, allo-HSCT leads to graft-versus-host disease (GVHD), a severe and often lethal immunological response, in the majority of transplant recipients. Current therapies for GVHD are limited and often reduce the effectiveness of allo-HSCT. Therefore, pro- and anti-inflammatory factors contributing to disease need to be explored in order to identify new treatment targets. Purinergic signalling plays important roles in haematopoiesis, inflammation and immunity, and recent evidence suggests that it can also affect haematopoietic stem cell transplantation and GVHD development. This review provides a detailed assessment of the emerging roles of purinergic receptors, most notably P2X7, P2Y2 and A2A receptors, and ectoenzymes, CD39 and CD73, in GVHD.
A Study on the Effect of Construction and Demolition Waste (CDW) Plastic Fractions on the Moisture and Resistance to Indentation of Wood-Polymer Composites (WPC)
Authors: Lahtela Ville , Kärki Timo
Published: August 2021

This paper investigated the moisture and strength properties of wood-polymer composites (WPC), which were made using three different recycled polymers using wood flour as filler. The recycled polymers were acrylonitrile butadiene styrene (ABS), polypropylene (PP), and polyethylene (PE), which were collected from among the construction and demolition waste (CDW) at a local waste management center. The commercial additives, such as a coupling agent and lubricant, were also included in the materials. Composite materials were manufactured with an agglomeration and an extrusion process. Water absorption and thickness swelling properties of composites, based on the recycled ABS and PE, were restricted compared to the recycled PP. The strength properties of WPC were determined with two methods, a traditional Brinell hardness and resistance to indentation. Using an ABS polymer as a matrix in the composite, the moisture and strength properties were improved. The recycled PP polymer caused these properties to be lowered, especially in the case of moisture properties. This study has shown that the method used can affect the measured value of certain properties. In addition, the sorting of recycled polymer fractions is desirable for the appearance of improved properties.