bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling Long-Term Monthly Rainfall Variability in Selected Provinces of South Africa: Trend and Extreme Value Analysis Approaches
Authors: Masingi Vusi Ntiyiso , Maposa Daniel
Published: April 2021

Extreme rainfall events have made significant damages to properties, public infrastructure and agriculture in some provinces of South Africa notably in KwaZulu-Natal and Gauteng among others. The general global increase in the frequency and intensity of extreme precipitation events in recent years is raising a concern that human activities might be heavily disturbed. This study attempts to model long-term monthly rainfall variability in the selected provinces of South Africa using various statistical techniques. The study investigates the normality and stationarity of the underlying distribution of the whole body of rainfall data for each selected province, the long-term trends of the rainfall data and the extreme value distributions which model the tails of the rainfall distribution data. These approaches were meant to help achieve the broader purpose of this study of investigating the long-term rainfall trends, stationarity of the rainfall distributions and extreme value distributions of monthly rainfall records in the selected provinces of South Africa in this era of climate change. The five provinces considered in this study are Eastern Cape, Gauteng, KwaZulu-Natal, Limpopo and Mpumalanga. The findings revealed that the long-term rainfall distribution for all the selected provinces does not come from a normal distribution. Furthermore, the monthly rainfall data distribution for the majority of the provinces is not stationary. The paper discusses the modelling of monthly rainfall extremes using the non-stationary generalised extreme value distribution (GEVD) which falls under the block maxima extreme value theory (EVT) approach. The maximum likelihood estimation method was used to obtain the estimates of the parameters. The stationary GEVD was found as the best distribution model for Eastern Cape, Gauteng, and KwaZulu-Natal provinces. Furthermore, model fitting supported non-stationary GEVD model for maximum monthly rainfall with nonlinear quadratic trend in the location parameter and a linear trend in the scale parameter for Limpopo, while in Mpumalanga the non-stationary GEVD model with a nonlinear quadratic trend in the scale parameter and no variation in the location parameter fitted well to the monthly rainfall data. The negative values of the shape parameters for Eastern Cape and Mpumalanga suggest that the data follow the Weibull distribution class, while the positive values of the shape parameters for Gauteng, KwaZulu-Natal and Limpopo suggest that the data follow the Fréchet distribution class. The findings from this paper could give information that can assist decision makers establish strategies for proper planning of agriculture, infrastructure, drainage system and other water resource applications in the South African provinces.
Mycobacterium tuberculosis-Induced Maternal Immune Activation Promotes Autism-Like Phenotype in Infected Mice Offspring
Authors: Manjeese Wadzanai , Mvubu Nontobeko E. , Steyn Adrie J. C. , Mpofana Thabisile
Published: April 2021

The maternal system’s exposure to pathogens during pregnancy influences fetal brain development causing a persistent inflammation characterized by elevated pro-inflammatory cytokine levels in offspring. Mycobacterium tuberculosis (Mtb) is a global pathogen that causes tuberculosis, a pandemic responsible for health and economic burdens. Although it is known that maternal infections increase the risk of autism spectrum disorder (ASD), it is not known whether Mtb infection is sufficient to induce ASD associated behaviors, immune dysregulation and altered expression of synaptic regulatory genes. The current study infected pregnant Balb/c mice with Mtb H37Rv and valproic acid (VPA) individually and in combination. Plasma cytokine profiles were measured in offspring using the Bio-plex Th17 pro mouse cytokine panel. Mtb infection increased plasma interleukin (IL)-6 and IL-17A, while tumor necrosis factor alpha (TNF-α), interferon (IFN)-γ and IL-1β were reduced when compared with saline. Mtb-induced maternal immune activation (MIA) offspring displayed increased grooming behavior. The study also revealed dysregulation in gene expression of synaptic molecules in the cerebellum. MIA rescued the VPA-induced effects on self-grooming and social interaction behaviors. Our finding therefore highlights a potential role of Mtb as a MIA agent that can potentially contribute to ASD.
The Interplay between Corporate Social Responsibility at Employee Level, Ethical Leadership, Quality of Work Life and Employee Pro-Environmental Behavior: The Case of Healthcare Organizations
Authors: Molnár Edina , Mahmood Asif , Ahmad Naveed , Ikram Amir , Murtaza Shah Ali
Published: April 2021

The notion of corporate social responsibility (CSR) has been around for many decades. However, even in 2021, its spectrum is still evolving. Several studies addressed CSR for realizing different organizational outcomes. However, its significance in achieving employee-related consequences is relatively new to the literature. In the same manner, it is not clear from existing literature how ethical leaders can impact their followers’ CSR-related behavior, for example, employee pro-environmental behavior (EPB). With this background, the current study aims to explore the relationship of CSR at the employee level (CSR-E) with EPB through the mediating effect of ethical leadership (ELS) in the healthcare sector of a developing economy. This study also proposes a conditional indirect effect of quality of work-life (QWL) in this relationship. The data for the current study were obtained from different hospitals located in a large city through a self-administered questionnaire. The data were examined through the structural equation modeling (SEM) technique. The results validated that CSR-E positively influences EPB, and ELS partially mediates this relationship. Furthermore, the results also confirmed the presence of the conditional indirect effect of QWL in the proposed relationship of the current study. These findings will be helpful for healthcare policymakers to enhance the pro-environmental behavior of employees at the workplace through CSR-E and ELS. These results will also be helpful in reducing the overall environmental footprint of a hospital.
Spatial and Temporal Characteristics of Environmental Air Quality and Its Relationship with Seasonal Climatic Conditions in Eastern China during 2015–2018
Authors: Wang Zhiyuan , Shi Xiaoyi , Pan Chunhua , Wang Sisi
Published: April 2021

Exploring the relationship between environmental air quality (EAQ) and climatic conditions on a large scale can help better understand the main distribution characteristics and the mechanisms of EAQ in China, which is significant for the implementation of policies of joint prevention and control of regional air pollution. In this study, we used the concentrations of six conventional air pollutants, i.e., carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), fine particulate matter (PM2.5), coarse particulate matter (PM10), and ozone (O3), derived from about 1300 monitoring sites in eastern China (EC) from January 2015 to December 2018. Exploiting the grading concentration limit (GB3095-2012) of various pollutants in China, we also calculated the monthly average air quality index (AQI) in EC. The results show that, generally, the EAQ has improved in all seasons in EC from 2015 to 2018. In particular, the concentrations of conventional air pollutants, such as CO, SO2, and NO2, have been decreasing year by year. However, the concentrations of particulate matter, such as PM2.5 and PM10, have changed little, and the O3 concentration increased from 2015 to 2018. Empirical mode decomposition (EOF) was used to analyze the major patterns of AQI in EC. The first mode (EOF1) was characterized by a uniform structure in AQI over EC. These phenomena are due to the precipitation variability associated with the East Asian summer monsoon (EASM), referred to as the “summer–winter” pattern. The second EOF mode (EOF2) showed that the AQI over EC is a north–south dipole pattern, which is bound by the Qinling Mountains and Huaihe River (about 35° N). The EOF2 is mainly caused by seasonal variations of the mixed concentration of PM2.5 and O3. Associated with EOF2, the Mongolia–Siberian High influences the AQI variation over northern EC by dominating the low-level winds (10 m and 850 hPa) in autumn and winter, and precipitation affects the AQI variation over southern EC in spring and summer.
Amyotrophic Lateral Sclerosis Risk, Family Income, and Fish Consumption Estimates of Mercury and Omega-3 PUFAs in the United States
Authors: Hoffman Hannah I. , Bradley Walter G. , Chen Celia Y. , Pioro Erik P. , Stommel Elijah W. , Andrew Angeline S.
Published: April 2021

Most amyotrophic lateral sclerosis (ALS) cases are considered sporadic, without a known genetic basis, and lifestyle factors are suspected to play an etiologic role. We previously observed increased risk of ALS associated with high nail mercury levels as an exposure biomarker and thus hypothesized that mercury exposure via fish consumption patterns increases ALS risk. Lifestyle surveys were obtained from ALS patients (n = 165) and n = 330 age- and sex-matched controls without ALS enrolled in New Hampshire, Vermont, or Ohio, USA. We estimated their annual intake of mercury and omega-3 polyunsaturated fatty acid (PUFA) via self-reported seafood consumption habits, including species and frequency. In our multivariable model, family income showed a significant positive association with ALS risk (p = 0.0003, adjusted for age, sex, family history, education, and race). Neither the estimated annual mercury nor omega-3 PUFA intakes via seafood were associated with ALS risk. ALS incidence is associated with socioeconomic status; however, consistent with a prior international study, this relationship is not linked to mercury intake estimated via fish or seafood consumption patterns.
The Diversity Efforts Disparity in Academic Medicine
Authors: Campbell Kendall M.
Published: April 2021

The diversity efforts disparity in academic medicine can be defined as part of the minority tax that negatively impacts faculty who are underrepresented in medicine. This disparity can be defined as differences between minority and non-minority faculty in their recruitment or assignment by the institution to address diversity issues, climate concerns and conflict around inclusion in academic medicine. It can manifest as disproportionate committee service, being asked to be the face of diversity for the school on websites or brochures or being asked to serve on diversity task forces or initiatives. In this article, the author further characterizes the diversity efforts disparity and provides recommendations for how to identify and address it in academic medicine.
Assessing the Feasibility of Providing a Family Skills Intervention, “Strong Families”, for Refugee Families Residing in Reception Centers in Serbia
Authors: El-Khani Aala , Haar Karin , Stojanovic Milos , Maalouf Wadih
Published: April 2021

War exposure and forced displacement threatens the wellbeing of caregivers and their children, leaving them at risk of negative outcomes, such as elevated rates of anxiety, depression and post-traumatic stress disorder. The importance of engaged, responsive and stable parenting for positive child wellbeing has been documented across diverse cultural and economic backgrounds. Despite the higher need for caregivers to be nurturing in challenging settings, they struggle to provide adequate support for their children due to lack of resources or their inability to deal with their own emotional challenges. A feasibility study was conducted of a new, open-access and light-touch family skills intervention, Strong Families (for families in humanitarian and challenged settings) on refugee families residing in Reception Centers in Serbia. Questionnaires and interviews were completed by participating caregivers and facilitators. Qualitative results indicated that the intervention was feasible to run in this humanitarian context, that caregivers viewed the intervention as culturally acceptable and complemented the quantitative results that showed promise for enhancing child behavior and family functioning tested indicators. Despite being a light intervention, Strong Families indicated improvement on child mental health, parenting practices and parent and family adjustment skills. Prioritizing family mental health and functioning as a primary need that parallels that of accessing physical medical care, sanitation and clean water must be the definitive next step in humanitarian aid.
Body Composition and Physical Health in Sports Practice: An Editorial
Authors: Toselli Stefania
Published: April 2021

The assessment of the health status of athletes, at all ages, is an aspect of fundamental importance, and, in recent years, the analysis of body composition has become a fundamental and essential part in its evaluation, such as in the optimization of sports performance [...]
HIV Related Knowledge, HIV Testing Decision-Making, and Perceptions of Alcohol Use as a Risk Factor for HIV among Black and African American Women
Authors: Walter Angela Wangari , Morocho Cesar
Published: April 2021

The HIV/AIDS epidemic disproportionately affects Black and African American women in the United States. This study examined the extent of HIV related knowledge, HIV testing decision-making, and perceptions of alcohol use as a risk factor for HIV among Black and African American women in urban and suburban communities. Seven focus groups were conducted with 37 women aged 18 to 49 residing in the Commonwealth of Massachusetts. Women participating in focus groups had a wide breadth of HIV related knowledge. Findings suggest the influence of interpersonal relationships and provider–patient interactions on HIV testing, the need for building community capacity and leveraging community resources towards HIV prevention, and the influence of alcohol outlet density on HIV vulnerability and exposure in communities of color. Comprehensive multifaceted evidence informed interventions that are culturally relevant and gender responsive are needed to reduce HIV/AIDS disparities.
Glucocorticoid Receptor: A Multifaceted Actor in Breast Cancer
Authors: Noureddine Lara Malik , Trédan Olivier , Hussein Nader , Badran Bassam , Le Romancer Muriel , Poulard Coralie
Published: April 2021

Breast cancer (BC) is one of the most common cancers in women worldwide. Even though the role of estrogen receptor alpha (ERα) is extensively documented in the development of breast tumors, other members of the nuclear receptor family have emerged as important players. Synthetic glucocorticoids (GCs) such as dexamethasone (dex) are commonly used in BC for their antiemetic, anti-inflammatory, as well as energy and appetite stimulating properties, and to manage the side effects of chemotherapy. However, dex triggers different effects depending on the BC subtype. The glucocorticoid receptor (GR) is also an important marker in BC, as high GR expression is correlated with a poor and good prognosis in ERα-negative and ERα-positive BCs, respectively. Indeed, though it drives the expression of pro-tumorigenic genes in ERα-negative BCs and is involved in resistance to chemotherapy and metastasis formation, dex inhibits estrogen-mediated cell proliferation in ERα-positive BCs. Recently, a new natural ligand for GR called OCDO was identified. OCDO is a cholesterol metabolite with oncogenic properties, triggering mammary cell proliferation in vitro and in vivo. In this review, we summarize recent data on GR signaling and its involvement in tumoral breast tissue, via its different ligands.
Nasal Epithelial Cell-Based Models for Individualized Study in Cystic Fibrosis
Authors: Keegan Duncan , Brewington John
Published: April 2021

The emergence of highly effective CFTR modulator therapy has led to significant improvements in health care for most patients with cystic fibrosis (CF). For some, however, these therapies remain inaccessible due to the rarity of their individual CFTR variants, or due to a lack of biologic activity of the available therapies for certain variants. One proposed method of addressing this gap is the use of primary human cell-based models, which allow preclinical therapeutic testing and physiologic assessment of relevant tissue at the individual level. Nasal cells represent one such tissue source and have emerged as a powerful model for individual disease study. The ex vivo culture of nasal cells has evolved over time, and modern nasal cell models are beginning to be utilized to predict patient outcomes. This review will discuss both historical and current state-of-the art use of nasal cells for study in CF, with a particular focus on the use of such models to inform personalized patient care.
Insights into the Functional Role of ADTRP (Androgen-Dependent TFPI-Regulating Protein) in Health and Disease
Authors: Lupu Cristina , Patel Maulin M. , Lupu Florea
Published: April 2021

The novel protein ADTRP, identified and described by us in 2011, is androgen-inducible and regulates the expression and activity of Tissue Factor Pathway Inhibitor, the major inhibitor of the Tissue Factor-dependent pathway of coagulation on endothelial cells. Single-nucleotide polymorphisms in ADTRP associate with coronary artery disease and myocardial infarction, and deep vein thrombosis/venous thromboembolism. Some athero-protective effects of androgen could exert through up-regulation of ADTRP expression. We discovered a critical role of ADTRP in vascular development and vessel integrity and function, manifested through Wnt signaling-dependent regulation of matrix metalloproteinase-9. ADTRP also hydrolyses fatty acid esters of hydroxy-fatty acids, which have anti-diabetic and anti-inflammatory effects and can control metabolic disorders. Here we summarize and analyze the knowledge on ADTRP and try to decipher its functions in health and disease.
Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review
Authors: Ohnishi Takashi , Ogawa Yuki , Suda Kota , Komatsu Miki , Harmon Satoko Matsumoto , Asukai Mitsuru , Takahata Masahiko , Iwasaki Norimasa , Minami Akio
Published: April 2021

Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.
Nanohydroxyapatite as a Biomaterial for Peripheral Nerve Regeneration after Mechanical Damage—In Vitro Study
Authors: Wiatrak Benita , Sobierajska Paulina , Szandruk-Bender Marta , Jawien Paulina , Janeczek Maciej , Dobrzynski Maciej , Pistor Patrycja , Szelag Adam , Wiglusz Rafal J.
Published: April 2021

Hydroxyapatite has been used in medicine for many years as a biomaterial or a cover for other biomaterials in orthopedics and dentistry. This study characterized the physicochemical properties (structure, particle size and morphology, surface properties) of Li+- and Li+/Eu3+-doped nanohydroxyapatite obtained using the wet chemistry method. The potential regenerative properties against neurite damage in cultures of neuron-like cells (SH-SY5Y and PC12 after differentiation) were also studied. The effect of nanohydroxyapatite (nHAp) on the induction of repair processes in cell cultures was assessed in tests of metabolic activity, the level of free oxygen radicals and nitric oxide, and the average length of neurites. The study showed that nanohydroxyapatite influences the increase in mitochondrial activity, which is correlated with the increase in the length of neurites. It has been shown that the doping of nanohydroxyapatite with Eu3+ ions enhances the antioxidant properties of the tested nanohydroxyapatite. These basic studies indicate its potential application in the treatment of neurite damage. These studies should be continued in primary neuronal cultures and then with in vivo models.
Matrix Metalloproteinases and Their Role in Mechanisms Underlying Effects of Quercetin on Heart Function in Aged Zucker Diabetic Fatty Rats
Authors: Boťanská Barbora , Barteková Monika , Ferenczyová Kristína , Fogarassyová Mária , Kindernay Lucia , Barančík Miroslav
Published: April 2021

Several mechanisms may contribute to cardiovascular pathology associated with diabetes, including dysregulation of matrix metalloproteinases (MMPs). Quercetin (QCT) is a substance with preventive effects in treatment of cardiovascular diseases and diabetes. The aim of the present study was to explore effects of chronic QCT administration on changes in heart function in aged lean and obese Zucker Diabetic Fatty (ZDF) rats and that in association with MMPs. Signaling underlying effects of diabetes and QCT were also investigated. In the study, we used one-year-old lean and obese ZDF rats treated for 6 weeks with QCT. Results showed that obesity worsened heart function and this was associated with MMP-2 upregulation, MMP-28 downregulation, and inhibition of superoxide dismutases (SODs). Treatment with QCT did not modulate diabetes-induced changes in heart function and MMPs. However, QCT activated Akt kinase and reversed effects of diabetes on SODs inhibition. In conclusion, worsened heart function due to obesity involved changes in MMP-2 and MMP-28 and attenuation of antioxidant defense by SOD. QCT did not have positive effects on improvement of heart function or modulation of MMPs. Nevertheless, its application mediated activation of adaptive responses against oxidative stress through Akt kinase and prevention of diabetes-induced negative effects on antioxidant defense by SODs.
In Sickness and in Health: The Immunological Roles of the Lymphatic System
Authors: Johnson Louise A.
Published: April 2021

The lymphatic system plays crucial roles in immunity far beyond those of simply providing conduits for leukocytes and antigens in lymph fluid. Endothelial cells within this vasculature are distinct and highly specialized to perform roles based upon their location. Afferent lymphatic capillaries have unique intercellular junctions for efficient uptake of fluid and macromolecules, while expressing chemotactic and adhesion molecules that permit selective trafficking of specific immune cell subsets. Moreover, in response to events within peripheral tissue such as inflammation or infection, soluble factors from lymphatic endothelial cells exert “remote control” to modulate leukocyte migration across high endothelial venules from the blood to lymph nodes draining the tissue. These immune hubs are highly organized and perfectly arrayed to survey antigens from peripheral tissue while optimizing encounters between antigen-presenting cells and cognate lymphocytes. Furthermore, subsets of lymphatic endothelial cells exhibit differences in gene expression relating to specific functions and locality within the lymph node, facilitating both innate and acquired immune responses through antigen presentation, lymph node remodeling and regulation of leukocyte entry and exit. This review details the immune cell subsets in afferent and efferent lymph, and explores the mechanisms by which endothelial cells of the lymphatic system regulate such trafficking, for immune surveillance and tolerance during steady-state conditions, and in response to infection, acute and chronic inflammation, and subsequent resolution.
A Yeast-Based Screening Unravels Potential Therapeutic Molecules for Mitochondrial Diseases Associated with Dominant ANT1 Mutations
Authors: di Punzio Giulia , Di Noia Maria Antonietta , Delahodde Agnès , Sellem Carole , Donnini Claudia , Palmieri Luigi , Lodi Tiziana , Dallabona Cristina
Published: April 2021

Mitochondrial diseases result from inherited or spontaneous mutations in mitochondrial or nuclear DNA, leading to an impairment of the oxidative phosphorylation responsible for the synthesis of ATP. To date, there are no effective pharmacological therapies for these pathologies. We performed a yeast-based screening to search for therapeutic drugs to be used for treating mitochondrial diseases associated with dominant mutations in the nuclear ANT1 gene, which encodes for the mitochondrial ADP/ATP carrier. Dominant ANT1 mutations are involved in several degenerative mitochondrial pathologies characterized by the presence of multiple deletions or depletion of mitochondrial DNA in tissues of affected patients. Thanks to the presence in yeast of the AAC2 gene, orthologue of human ANT1, a yeast mutant strain carrying the M114P substitution equivalent to adPEO-associated L98P mutation was created. Five molecules were identified for their ability to suppress the defective respiratory growth phenotype of the haploid aac2M114P. Furthermore, these molecules rescued the mtDNA mutability in the heteroallelic AAC2/aac2M114P strain, which mimics the human heterozygous condition of adPEO patients. The drugs were effective in reducing mtDNA instability also in the heteroallelic strain carrying the R96H mutation equivalent to the more severe de novo dominant missense mutation R80H, suggesting a general therapeutic effect on diseases associated with dominant ANT1 mutations.
The Role of Marrow Microenvironment in the Growth and Development of Malignant Plasma Cells in Multiple Myeloma
Authors: Giannakoulas Nikolaos , Ntanasis-Stathopoulos Ioannis , Terpos Evangelos
Published: April 2021

The development and effectiveness of novel therapies in multiple myeloma have been established in large clinical trials. However, multiple myeloma remains an incurable malignancy despite significant therapeutic advances. Accumulating data have elucidated our understanding of the genetic background of the malignant plasma cells along with the role of the bone marrow microenvironment. Currently, the interaction among myeloma cells and the components of the microenvironment are considered crucial in multiple myeloma pathogenesis. Adhesion molecules, cytokines and the extracellular matrix play a critical role in the interplay among genetically transformed clonal plasma cells and stromal cells, leading to the proliferation, progression and survival of myeloma cells. In this review, we provide an overview of the multifaceted role of the bone marrow microenvironment in the growth and development of malignant plasma cells in multiple myeloma.
A Role for TGFβ Signaling in Preclinical Osteolytic Estrogen Receptor-Positive Breast Cancer Bone Metastases Progression
Authors: Cheng Julia N. , Frye Jennifer B. , Whitman Susan A. , Kunihiro Andrew G. , Pandey Ritu , Funk Janet L.
Published: April 2021

While tumoral Smad-mediated transforming growth factor β (TGFβ) signaling drives osteolytic estrogen receptor α-negative (ER-) breast cancer bone metastases (BMETs) in preclinical models, its role in ER+ BMETs, representing the majority of clinical BMETs, has not been documented. Experiments were undertaken to examine Smad-mediated TGFβ signaling in human ER+ cells and bone-tropic behavior following intracardiac inoculation of estrogen (E2)-supplemented female nude mice. While all ER+ tumor cells tested (ZR-75-1, T47D, and MCF-7-derived) expressed TGFβ receptors II and I, only cells with TGFβ-inducible Smad signaling (MCF-7) formed osteolytic BMETs in vivo. Regulated secretion of PTHrP, an osteolytic factor expressed in >90% of clinical BMETs, also tracked with osteolytic potential; TGFβ and E2 each induced PTHrP in bone-tropic or BMET-derived MCF-7 cells, with the combination yielding additive effects, while in cells not forming BMETs, PTHrP was not induced. In vivo treatment with 1D11, a pan-TGFβ neutralizing antibody, significantly decreased osteolytic ER+ BMETs in association with a decrease in bone-resorbing osteoclasts at the tumor-bone interface. Thus, TGFβ may also be a driver of ER+ BMET osteolysis. Moreover, additive pro-osteolytic effects of tumoral E2 and TGFβ signaling could at least partially explain the greater propensity for ER+ tumors to form BMETs, which are primarily osteolytic.
Photoreactivity of Hair Melanin from Different Skin Phototypes—Contribution of Melanin Subunits to the Pigments Photoreactive Properties
Authors: Mokrzynski Krystian , Ito Shosuke , Wakamatsu Kazumasa , Camenish Theodore G. , Sarna Tadeusz , Sarna Michal
Published: April 2021

Photoreactivity of melanin has become a major focus of research due to the postulated involvement of the pigment in UVA-induced melanoma. However, most of the hitherto studies were carried out using synthetic melanin models. Thus, photoreactivity of natural melanins is yet to be systematically analyzed. Here, we examined the photoreactive properties of natural melanins isolated from hair samples obtained from donors of different skin phototypes (I, II, III, and V). X-band and W-band electron paramagnetic resonance (EPR) spectroscopy was used to examine the paramagnetic properties of the pigments. Alkaline hydrogen peroxide degradation and hydroiodic acid hydrolysis were used to determine the chemical composition of the melanins. EPR oximetry and spin trapping were used to examine the oxygen photoconsumption and photo-induced formation of superoxide anion, and time-resolved near infrared phosphorescence was employed to determine the singlet oxygen photogeneration by the melanins. The efficiency of superoxide and singlet oxygen photogeneration was related to the chemical composition of the studied melanins. Melanins from blond and chestnut hair (phototypes II and III) exhibited highest photoreactivity of all examined pigments. Moreover, melanins of these phototypes showed highest quantum efficiency of singlet oxygen photogeneration at 332 nm and 365 nm supporting the postulate of the pigment contribution in UVA-induced melanoma.
Melanin Transfer in the Epidermis: The Pursuit of Skin Pigmentation Control Mechanisms
Authors: Moreiras Hugo , Seabra Miguel C. , Barral Duarte C.
Published: April 2021

The mechanisms by which the pigment melanin is transferred from melanocytes and processed within keratinocytes to achieve skin pigmentation remain ill-characterized. Nevertheless, several models have emerged in the past decades to explain the transfer process. Here, we review the proposed models for melanin transfer in the skin epidermis, the available evidence supporting each one, and the recent observations in favor of the exo/phagocytosis and shed vesicles models. In order to reconcile the transfer models, we propose that different mechanisms could co-exist to sustain skin pigmentation under different conditions. We also discuss the limited knowledge about melanin processing within keratinocytes. Finally, we pinpoint new questions that ought to be addressed to solve the long-lasting quest for the understanding of how basal skin pigmentation is controlled. This knowledge will allow the emergence of new strategies to treat pigmentary disorders that cause a significant socio-economic burden to patients and healthcare systems worldwide and could also have relevant cosmetic applications.
Beyond Dopamine Receptor Antagonism: New Targets for Schizophrenia Treatment and Prevention
Authors: Gomes Felipe V. , Grace Anthony A.
Published: April 2021

Treatment of schizophrenia (SCZ) historically relies on the use of antipsychotic drugs to treat psychosis, with all of the currently available antipsychotics acting through the antagonism of dopamine D2 receptors. Although antipsychotics reduce psychotic symptoms in many patients, they induce numerous undesirable effects and are not effective against negative and cognitive symptoms. These highlight the need to develop new drugs to treat SCZ. An advanced understanding of the circuitry of SCZ has pointed to pathological origins in the excitation/inhibition balance in regions such as the hippocampus, and restoring function in this region, particularly as a means to compensate for parvalbumin (PV) interneuron loss and resultant hippocampal hyperactivity, may be a more efficacious approach to relieve a broad range of SCZ symptoms. Other targets, such as cholinergic receptors and the trace amine-associated receptor 1 (TAAR1), have also shown some promise for the treatment of SCZ. Importantly, assessing efficacy of novel compounds must take into consideration treatment history of the patient, as preclinical studies suggest prior antipsychotic treatment may interfere with the efficacy of these novel agents. However, while novel therapeutic targets may be more effective in treating SCZ, a more effective approach would be to prevent the transition to SCZ in susceptible individuals. A focus on stress, which has been shown to be a predisposing factor in risk for SCZ, is a possible avenue that has shown promise in preclinical studies. Therefore, therapeutic approaches based on our current understanding of the circuitry of SCZ and its etiology are likely to enable development of more effective therapeutic interventions for this complex disorder.
Skeletal Muscle–Adipose Tissue–Tumor Axis: Molecular Mechanisms Linking Exercise Training in Prostate Cancer
Authors: Rocha-Rodrigues Sílvia , Matos Andreia , Afonso José , Mendes-Ferreira Miguel , Abade Eduardo , Teixeira Eduardo , Silva Bruno , Murawska-Ciałowicz Eugenia , Oliveira Maria José , Ribeiro Ricardo
Published: April 2021

Increased visceral adiposity may influence the development of prostate cancer (PCa) aggressive tumors and cancer mortality. White adipose tissue (WAT), usually referred to as periprostatic adipose tissue (PPAT), surrounds the prostatic gland and has emerged as a potential mediator of the tumor microenvironment. Exercise training (ET) induces several adaptations in both skeletal muscle and WAT. Some of these effects are mediated by ET-induced synthesis and secretion of several proteins, known as myo- and adipokines. Together, myokines and adipokines may act in an endocrine-like manner to favor communication between skeletal muscle and WAT, as they may work together to improve whole-body metabolic health. This crosstalk may constitute a potential mechanism by which ET exerts its beneficial role in the prevention and treatment of PCa-related disorders; however, this has not yet been explored. Therefore, we reviewed the current evidence on the effects of skeletal muscle–WAT–tumor crosstalk in PCa, and the potential mediators of this process to provide a better understanding of underlying ET-related mechanisms in cancer.
Candida auris: A Quick Review on Identification, Current Treatments, and Challenges
Authors: Černáková Lucia , Roudbary Maryam , Brás Susana , Tafaj Silva , Rodrigues Célia F.
Published: April 2021

Candida auris is a novel and major fungal pathogen that has triggered several outbreaks in the last decade. The few drugs available to treat fungal diseases, the fact that this yeast has a high rate of multidrug resistance and the occurrence of misleading identifications, and the ability of forming biofilms (naturally more resistant to drugs) has made treatments of C. auris infections highly difficult. This review intends to quickly illustrate the main issues in C. auris identification, available treatments and the associated mechanisms of resistance, and the novel and alternative treatment and drugs (natural and synthetic) that have been recently reported.
Should We Be Concerned about How Information Privacy Concerns Are Measured in Online Contexts? A Systematic Review of Survey Scale Development Studies
Authors: Bartol Jošt , Vehovar Vasja , Petrovčič Andraž
Published: April 2021

This systematic review addresses problems identified in existing research on survey measurements of individuals’ information privacy concerns in online contexts. The search in this study focused on articles published between 1996 and 2019 and yielded 970 articles. After excluding duplicates and screening for eligibility, we were left with 13 articles in which the investigators developed a total of 16 survey scales. In addition to reviewing the conceptualizations, contexts, and dimensionalities of the scales, we evaluated the quality of methodological procedures used in the scale development process, drawing upon the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) Risk of Bias checklist. The results confirmed that the breadth of conceptualizations and dimensions of information privacy concerns are constructed with a low emphasis on contextuality. Assessment of the quality of methodological procedures suggested a need for a more thorough evaluation of content validity. We provide several recommendations for tackling these issues and propose new research directions.
Urinary Proteomics Reveals Promising Biomarkers in Menstrually Related and Post-Menopause Migraine
Authors: Bellei Elisa , Bergamini Stefania , Rustichelli Cecilia , Monari Emanuela , Dal Porto Michele , Fiorini Alessandro , Tomasi Aldo , Ferrari Anna
Published: April 2021

Migraine is an invalidating neuro-vascular disorder largely spread in the world population. Currently, its pathophysiology is not yet completely understood. The purpose of this study was to investigate the urinary proteome of women suffering from menstrually related migraine (MM) and post-menopause migraine (PM) in comparison with non-headache women as controls, to search potential biomarkers of these migraine sub-types. Urine samples were analyzed by mono-dimensional gel electrophoresis (SDS-PAGE) and two-dimensional gel electrophoresis (2DE) coupled to liquid chromatography-mass spectrometry (LC-MS/MS). Twenty-one urinary proteins were found significantly dysregulated in MM and PM (p < 0.05). The STRING Analysis database revealed interaction between 15 proteins, which were mainly involved in the immune and inflammatory response. Seven of the most considerable proteins were further quantified by western blot: protein S100A8 (S10A8), up-regulated in MM, uromodulin (UROM), alpha-1-microglobulin (AMBP), gelsolin (GELS), prostaglandin-H2 D-isomerase (PTGDS), over-expressed in PM, apolipoprotein A-I (APOA1), and transthyretin (TTHY), respectively down- and up-regulated in both migraineur groups vs controls. These candidate biomarkers might be involved in the neurophysiological network of MM and PM, thus helping to better understand the pathophysiology of these migraine forms. If validated in large-scale studies, this protein cluster could become a distinctive target for clinical applications in migraine diagnosis and treatment.
Quantitative Flow Ratio Is Related to Intraluminal Coronary Stenosis Parameters as Assessed with Optical Coherence Tomography
Authors: Milzi Andrea , Dettori Rosalia , Burgmaier Kathrin , Marx Nikolaus , Reith Sebastian , Burgmaier Mathias
Published: April 2021

Background: Quantitative flow ratio (QFR) is a novel method for assessing hemodynamic relevance of a coronary lesion based on angiographic projections without the need of a pressure wire. Various studies demonstrated that QFR consistently related to fractional flow reserve (FFR); however, it is still unclear to what extent QFR reflects intraluminal stenosis parameters. Given that optical coherence tomography (OCT) is currently the gold standard to assess intraluminal stenosis parameters, we investigated the relationship between OCT-derived lesion geometry and QFR. Methods: We determined QFR in 97 lesions from 87 patients who underwent coronary angiography and OCT due to stable angina. QFR was measured with proprietary software and compared with OCT-based assessment of intraluminal stenosis parameters as well as lesion morphology. Results: Mean QFR was 0.79 ± 0.10. QFR demonstrated a consistent association with FFR (r = 0.834, p < 0.001). Interestingly, QFR was associated with OCT-derived parameters such as minimal lumen area (MLA, r = 0.390, p = 0.015), percent area stenosis (r = 0.412, p < 0.001), minimal lumen diameter (MLD, r = 0.395, p < 0.001), and percent diameter stenosis (r = 0.400, p < 0.001). Both minimal luminal area (ROC = 0.734, optimal cut-off 1.75 mm2) and minimal luminal diameter (ROC = 0.714, optimal cut-off 1.59 mm) presented a good diagnostic accuracy in diagnosing hemodynamic relevance (QFR ≤ 0.80). There was no significant association between QFR and anatomic features of plaque vulnerability. Conclusion: OCT-derived intraluminal stenosis parameters are related to QFR values and predict hemodynamic lesion relevance. The data supports the validity of QFR as 3D-vessel reconstruction method to assess coronary physiology without the need of a pressure wire.
Output Feedback Cooperative Dynamic Positioning Control for an Unactuated Floating Object Using Multiple Vessels
Authors: Xia Guoqing , Sun Chuang , Zhao Bo
Published: April 2021

This paper proposes an output feedback cooperative dynamic positioning control scheme for an unactuated floating object using multiple vessels under model uncertainties and environmental disturbances. The floating object is connected to multiple vessels through towlines. At first, nonlinear extended state observers are developed for the floating object and vessels to reconstruct the unmeasured velocity and to estimate the model uncertainties and disturbances. Second, observer-based controllers are designed for the floating object and vessels to drive the floating object to track the reference signal and to achieve the cooperative control of multiple vessels, respectively. The salient features of the proposed control scheme are presented as follows. Firstly, by design the object controller, the tracking performance of the object is improved. Secondly, according to the required force of the floating object, the time-varying formation of vessels is obtained by using the towline attachment geometry of the floating object, control allocation and a towline model. It is shown that all signals in closed-loop system are bounded via Lyapunov analysis. Simulation study is carried out to verify the effectiveness of proposed control method.
Weevil Borers Affect the Spatio-Temporal Dynamics of Banana Fusarium Wilt
Authors: Heck Daniel W. , Alves Gabriel , Mizubuti Eduardo S. G.
Published: April 2021

Dispersal of propagules of a pathogen has remarkable effects on the development of epidemics. Previous studies suggested that insect pests play a role in the development of Fusarium wilt (FW) epidemics in banana fields. We provided complementary evidence for the involvement of two insect pests of banana, the weevil borer (Cosmopolites sordidus L., WB) and the false weevil borer (Metamasius hemipterus L., FWB), in the dispersal of Fusarium oxysporum f. sp. cubense (Foc) using a comparative epidemiology approach under field conditions. Two banana plots located in a field with historical records of FW epidemics were used; one was managed with Beauveria bassiana to reduce the population of weevils, and the other was left without B. bassiana applications. The number of WB and FWB was monitored biweekly and the FW incidence was quantified bimonthly during two years. The population of WB and the incidence (6.7%) of FW in the plot managed with B. bassiana were lower than in the plot left unmanaged (13%). The monomolecular model best fitted the FW disease progress data, and as expected, the average estimated disease progress rate was lower in the plot managed with the entomopathogenic fungus (r = 0.002) compared to the unmanaged plot (r = 0.006). Aggregation of FW was higher in the field with WB management. WB affected the spatial and temporal dynamics of FW epidemics under field conditions. Management of the insects may reduce yield loss due to FW.
Coastal Scenic Beauty and Sensitivity at the Balearic Islands, Spain: Implication of Natural and Human Factors
Authors: Mooser Alexis , Anfuso Giorgio , Gómez-Pujol Lluís , Rizzo Angela , Williams Allan T. , Aucelli Pietro P. C.
Published: April 2021

Coastal areas globally are facing a significant range of environmental stresses, enhanced by climate change-related processes and a continuous increase of human activities. The economic benefits of tourism are well-known for coastal regions, but, very often, conflicts arise between short-term benefits and long-term conservation goals. Among beach user preferences, five parameters of greater importance stand out from the rest, i.e., safety, facilities, water quality, litter and scenery; the latter is the main concern of this study. A coastal scenic evaluation was carried out in the Balearic Islands and focused on two major issues: coastal scenic beauty together with sensitivity to natural processes and human pressure. The archipelago is renowned as a top international coastal tourist destination that receives more than 13.5 million visitors (2019). Impressive landscape diversity makes the Balearics Islands an ideal field for this research. In total, 52 sites, respectively located in Ibiza (11), Formentera (5), Mallorca (18) and Menorca (18), were field-tested. In a first step, coastal scenic beauty was quantified using the coastal scenic evaluation system (CSES) method, based on the evaluation of 26 physical and human parameters, and using weighting matrices parameters and fuzzy logic mathematics. An evaluation index (“D”) was obtained for each site, allowing one to classify them in one of the five scenic classes established by the method. Twenty-nine sites were included in class I, corresponding to extremely attractive sites (CSES), which were mainly observed in Menorca. Several sound measures were proposed to maintain and/or enhance sites’ scenic value. In a second step, scenic sensitivity was evaluated using a novel methodological approach that makes possible the assessment of three different coastal scenic sensitivity indexes (CSSI), i.e., the natural sensitivity index NSI, the human sensitivity index HSI and the total sensitivity index TSI. Future climate change trends and projection of tourism development, studied at municipality scale, were considered as correction factors. All the islands showed places highly sensitive to environmental processes, while sensitivity to human pressure was essentially observed at Ibiza and Mallorca. Thereafter, sites were categorized into one of three sensitive groups established by the methodology. Results obtained are useful in pointing out very sensitive sceneries as well as limiting, preventing and/or anticipating future scenic degradation linked to natural and human issues.