bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of a Ventilation System for Energy Efficiency and Indoor Environmental Quality in a Renovated Historical Building: A Case Study
Authors: Nagy Richard , Mečiarová Ľudmila , Vilčeková Silvia , Krídlová Burdová Eva , Košičanová Danica
Published: October 2019

This paper emphasizes the importance of environmental protection regarding the reduction of energy consumption while maintaining living standards. The aim of the research is to observe the effects of mechanical and natural ventilation on energy consumption and building operation as well as indoor environmental quality (IEQ). The results of indoor environmental quality testing show that the mean relative humidity (31%) is in the permissible range (30%–70%); the mean CO2 concentration (1050.5 ppm) is above the recommended value of 1000 ppm according to Pettenkofer; and the mean PM10 concentration (43.5 µg/m3) is under the limit value of 50 µg/m3. A very large positive correlation is found between relative humidity and concentration of CO2 as well as between the concentration of PM5 and the concentration of CO2. The most commonly occurring sick building syndrome (SBS) symptoms are found to be fatigue and the feeling of a heavy head.
Determinants of Smoking Status in a Sample of Outpatients Afferent to a Tertiary Referral Hospital
Authors: Radaeli Alessandro , Nardin Matteo , Azzolina Danila , Malerba Mario
Published: October 2019

The identification of determinants of attempts to quit smoking and quitting smoking success is crucial for effective smoking prevention and/or cessation programs. Thus, here we have conducted a survey to determine the sociodemographic characteristics of tobacco use and the potential determinants of quitting smoking among a population of 140 subjects—101 smokers and 39 ex-smokers—referred to our clinic for respiratory diseases. Subject characteristics included demographic data, employment and education status, respiratory disease family history, smoking habits, life habits, diet, alcohol intake, and physical activity. In comparison with former smokers, active smokers were younger, lived with at least one smoking family member, and were more frequently exposed to passive smoke. They also displayed a higher coffee consumption, a higher frequency of in-between-meal snacks, and a lower chronic obstructive pulmonary disease (COPD) prevalence. In comparison with subjects who had never attempted to quit smoking, individuals who had attempted to quit smoking were younger, had a lower pack-year median, consumed a higher amount of coffee and alcohol, and conducted regular physical activity. Determinants of successful smoking cessation were older age, lower passive smoking exposure and daily coffee intake, and COPD diagnosis. Overall, our findings underscore the importance of health education in fostering successful smoking cessation in respiratory disease patients.
A Detoxification Intervention for Gulf War Illness: A Pilot Randomized Controlled Trial
Authors: Kerr Kathleen , Morse Gayle , Graves Donald , Zuo Fei , Lipowicz Alain , Carpenter David O.
Published: October 2019

Approximately 30% of the 700,000 US veterans of the 1990–1991 Persian Gulf War developed multiple persistent symptoms called Gulf War illness. While the etiology is uncertain, several toxic exposures including pesticides and chemical warfare agents have shown associations. There is no effective medical treatment. An intervention to enhance detoxification developed by Hubbard has improved quality of life and/or reduced body burdens in other cohorts. We evaluated its feasibility and efficacy in ill Gulf War (GW) veterans in a randomized, waitlist-controlled, pilot study at a community-based rehabilitation facility in the United States. Eligible participants (n = 32) were randomly assigned to the intervention (n = 22) or a four-week waitlist control (n = 10). The daily 4–6 week intervention consisted of exercise, sauna-induced sweating, crystalline nicotinic acid and other supplements. Primary outcomes included recruitment, retention and safety; and efficacy was measured via Veteran’s Short Form-36 (SF-36) quality of life, McGill pain, multidimensional fatigue inventory questionnaires and neuropsychological batteries. Scoring of outcomes was blinded. All 32 completed the trial and 21 completed 3-month follow-up. Mean SF-36 physical component summary score after the intervention was 6.9 (95% CI; −0.3, 14.2) points higher compared to waitlist control and 11 of 16 quality of life, pain and fatigue measures improved, with no serious adverse events. Most improvements were retained after 3 months. The Hubbard regimen was feasible, safe and might offer relief for symptoms of GW illness.
Addressing Cardiovascular Health Disparities in Minnesota: Establishment of a Community Steering Committee by FAITH! (Fostering African-American Improvement in Total Health)
Authors: Manjunath Chandrika , Ifelayo Oluwatomilona , Jones Clarence , Washington Monisha , Shanedling Stanton , Williams Johnnie , Patten Christi A. , Cooper Lisa A. , Brewer LaPrincess C.
Published: October 2019

Despite its rank as the fourth healthiest state in the United States, Minnesota has clear cardiovascular disease disparities between African-Americans and whites. Culturally-tailored interventions implemented using community-based participatory research (CBPR) principles have been vital to improving health and wellness among African-Americans. This paper delineates the establishment, impact, and lessons learned from the formation of a community steering committee (CSC) to guide the Fostering African-American Improvement in Total Health (FAITH!) Program, a CBPR cardiovascular health promotion initiative among African-Americans in Minnesota. The theory-informed CSC implementation process included three phases: (1) Membership Formation and Recruitment, (2) Engagement, and (3) Covenant Development and Empowerment. The CSC is comprised of ten diverse community members guided by mutually agreed upon bylaws in their commitment to FAITH!. Overall, members considered the CSC implementation process effective and productive. A CBPR conceptual model provided an outline of proximal and distal goals for the CSC and FAITH!. The CSC implementation process yielded four lessons learned: (1) Have clarity of purpose and vision, (2) cultivate group cohesion, (3) employ consistent review of CBPR tenets, and (4) expect the unexpected. A robust CSC was established and was instrumental to the success and impact of FAITH! within African-American communities in Minnesota.
A Multifactorial Approach to Sleep and Its Association with Health-Related Quality of Life in a Multiethnic Asian Working Population: A Cross-Sectional Analysis
Authors: Dunleavy Gerard , Tonon André Comiran , Chua Ai Ping , Zhang Yichi , Cheung Kei Long , Thach Thuan-Quoc , Rykov Yuri , Soh Chee-Kiong , Christopoulos Georgios , de Vries Hein , Car Josip
Published: October 2019

This study aims to explore if objectively and subjectively measured sleep parameters are associated with physical and mental health-related quality of life in a multiethnic working population in Singapore. We performed a cross-sectional analysis with data from 329 full-time employees enrolled in a workplace cohort study in Singapore. The Short-Form 36v2 (SF-36v2) survey was used to assess health-related quality of life, in terms of physical and mental health. Subjective and objective sleep parameters were measured using the Pittsburgh Sleep Quality Index and wrist actigraphy, respectively. Generalized linear modeling was performed to examine the association between sleep parameters and health-related quality of life. After adjusting for confounders, subjectively measured sleep disturbances were associated with a lower physical health-related quality of life, whereas higher, objectively measured sleep efficiency was associated with greater physical health-related quality of life. Subjectively measured daytime dysfunction was associated with impaired mental health-related quality of life. Using both objective and subjective measurements of sleep, the current study suggests that there is an association between sleep and health-related quality of life. Workplace health-promotion planners in Singapore should consider programmes that educate workers on better sleep hygiene practices in an effort to improve sleep and health-related quality of life.
Combined 2D-QSAR, Principal Component Analysis and Sensitivity Analysis Studies on Fluoroquinolones’ Genotoxicity
Authors: Du Meijin , Zhang Dan , Hou Yilin , Zhao Xiaohui , Li Yu
Published: October 2019

In this paper, two-dimensional quantitative structure–activity relationship (2D-QSAR) and principal component analysis (PCA) methods were employed to screen the main parameters affecting the genotoxicity of fluoroquinolones (FQs), and the rules affecting the genetic toxicity of FQs were investigated by combining 2D-QSAR and PCA with the sensitivity analysis method. First, four types of parameters were calculated, namely, the geometric parameters (7), electronic parameters (5), physical and chemical parameters (8), and spectral parameters (7), but the physical and chemical parameters heat of formation (HF) and critical volume (CV) were excluded after the establishment of the 2D-QSAR model. Then, after PCA, it was found that the first principal component represented the main driving factors affecting the molecular genetic toxicity of FQs. In addition, after comprehensive analysis of the factor loading of the first, second, and third principal components, seven parameters affecting the genotoxicity of the FQs were screened out, namely, total energy (TE), critical temperature (CT), and molecular weight (Mol Wt) (increased with increasing genotoxicity of the FQs) and steric parameter (MR), quadrupole moment QXX (QXX), quadrupole moment QYY (QYY), and boiling point (BP) (decreased with increasing genotoxicity of the FQs); the above key parameters were also verified by sensitivity analysis. The obtained rules could be used to determine the substitution sites and the substitution groups associated with higher genotoxicity in the process of FQ modification, and these rules agreed well with the hologram quantitative structure–activity relationship (HQSAR) model. Finally, it was also found through SPSS analysis that the parameters screened in this paper were significantly correlated with FQ derivatives’ genetic toxicity.
Juvenile Huntington’s Disease Skin Fibroblasts Respond with Elevated Parkin Level and Increased Proteasome Activity as a Potential Mechanism to Counterbalance the Pathological Consequences of Mutant Huntingtin Protein
Authors: Aladdin Azzam , Király Róbert , Boto Pal , Regdon Zsolt , Tar Krisztina
Published: October 2019

Huntington’s disease (HD) is an inherited neurodegenerative disorder, caused by an abnormal polyglutamine (polyQ) expansion in the huntingtin protein (Htt). Mitochondrial dysfunction and impairment of the ubiquitin-proteasome system (UPS) are hallmarks of HD neurons. The extraneural manifestations of HD are still unclear. We investigated the crosstalk between mitochondria and proteolytic function in skin fibroblasts from juvenile HD patients. We found reduced mitosis, increased cell size, elevated ROS and increased mitochondrial membrane potential in juvenile HD fibroblasts, while cellular viability was maintained. Mitochondrial OXPHOS analysis did not reveal significant differences compared to control. However, the level of mitochondrial fusion and fission proteins was significantly lower and branching in the mitochondria network was reduced. We hypothesized that juvenile HD fibroblasts counterbalance cellular damage and mitochondrial network deficit with altered proteasome activity to promote cell survival. Our data reveal that juvenile HD fibroblasts exhibit higher proteasome activity, which was associated with elevated gene and protein expression of parkin. Moreover, we demonstrate elevated proteasomal degradation of the mitochondrial fusion protein Mfn1 in diseased cells compared to control cells. Our data suggest that juvenile HD fibroblasts respond to mutant polyQ expansion of Htt with enhanced proteasome activity and faster turnover of specific UPS substrates to protect cells.
What Does the History of Research on the Repair of DNA Double-Strand Breaks Tell Us?—A Comprehensive Review of Human Radiosensitivity
Authors: Berthel Elise , Ferlazzo Mélanie L. , Devic Clément , Bourguignon Michel , Foray Nicolas
Published: October 2019

Our understanding of the molecular and cellular response to ionizing radiation (IR) has progressed considerably. This is notably the case for the repair and signaling of DNA double-strand breaks (DSB) that, if unrepaired, can result in cell lethality, or if misrepaired, can cause cancer. However, through the different protocols, techniques, and cellular models used during the last four decades, the DSB repair kinetics and the relationship between cellular radiosensitivity and unrepaired DSB has varied drastically, moving from all-or-none phenomena to very complex mechanistic models. To date, personalized medicine has required a reliable evaluation of the IR-induced risks that have become a medical, scientific, and societal issue. However, the molecular bases of the individual response to IR are still unclear: there is a gap between the moderate radiosensitivity frequently observed in clinic but poorly investigated in the publications and the hyper-radiosensitivity of rare but well-characterized genetic diseases frequently cited in the mechanistic models. This paper makes a comprehensive review of semantic issues, correlations between cellular radiosensitivity and unrepaired DSB, shapes of DSB repair curves, and DSB repair biomarkers in order to propose a new vision of the individual response to IR that would be more coherent with clinical reality.
Renal Ca2+ and Water Handling in Response to Calcium Sensing Receptor Signaling: Physiopathological Aspects and Role of CaSR-Regulated microRNAs
Authors: Ranieri Marianna
Published: October 2019

Calcium (Ca2+) is a universal and vital intracellular messenger involved in a diverse range of cellular and biological processes. Changes in the concentration of extracellular Ca2+ can disrupt the normal cellular activities and the physiological function of these systems. The calcium sensing receptor (CaSR) is a unique G protein-coupled receptor (GPCR) activated by extracellular Ca2+ and by other physiological cations, aminoacids, and polyamines. CaSR is the main controller of the extracellular Ca2+ homeostatic system by regulating parathyroid hormone (PTH) secretion and, in turn, Ca2+ absorption and resorption. Recent advances highlight novel signaling pathways activated by CaSR signaling involving the regulation of microRNAs (miRNAs). miRNAs are naturally-occurring small non-coding RNAs that regulate post-transcriptional gene expression and are involved in several diseases. We previously described that high luminal Ca2+ in the renal collecting duct attenuates short-term vasopressin-induced aquaporin-2 (AQP2) trafficking through CaSR activation. Moreover, we demonstrated that CaSR signaling reduces AQP2 abundance via AQP2-targeting miRNA-137. This review summarizes the recent data related to CaSR-regulated miRNAs signaling pathways in the kidney.
Discrimination of DNA Methylation Signal from Background Variation for Clinical Diagnostics
Authors: Sanchez Robersy , Yang Xiaodong , Maher Thomas , Mackenzie Sally A.
Published: October 2019

Advances in the study of human DNA methylation variation offer a new avenue for the translation of epigenetic research results to clinical applications. Although current approaches to methylome analysis have been helpful in revealing an epigenetic influence in major human diseases, this type of analysis has proven inadequate for the translation of these advances to clinical diagnostics. As in any clinical test, the use of a methylation signal for diagnostic purposes requires the estimation of an optimal cutoff value for the signal, which is necessary to discriminate a signal induced by a disease state from natural background variation. To address this issue, we propose the application of a fundamental signal detection theory and machine learning approaches. Simulation studies and tests of two available methylome datasets from autism and leukemia patients demonstrate the feasibility of this approach in clinical diagnostics, providing high discriminatory power for the methylation signal induced by disease, as well as high classification performance. Specifically, the analysis of whole biomarker genomic regions could suffice for a diagnostic, markedly decreasing its cost.
Autosomal Dominant Retinitis Pigmentosa Due to Class B Rhodopsin Mutations: An Objective Outcome for Future Treatment Trials
Authors: Sumaroka Alexander , Cideciyan Artur V. , Charng Jason , Wu Vivian , Powers Christian A. , Iyer Bhavya S. , Lisi Brianna , Swider Malgorzata , Jacobson Samuel G.
Published: October 2019

Gene therapy for adRP due to RHO mutations was recently shown to prevent photoreceptor death in a canine model of Class B disease. Among translational steps to be taken, one is to determine a method to detect efficacy in a human clinical trial. The relatively slow progression of adRP becomes a difficulty for clinical trials requiring an answer to whether there is slowed progression of degeneration in response to therapy. We performed a single-center, retrospective observational study of cross-sectional and longitudinal data. The study was prompted by our identification of a pericentral disease distribution in Class B RHO-adRP. Ultrawide optical coherence tomography (OCT) scans were used. Inferior retinal pericentral defects was an early disease feature. Degeneration further inferior in the retina merged with the pericentral defect, which extended into superior retina. In about 70% of patients, there was an asymmetric island of structure with significantly greater superior than inferior ellipsoid zone (EZ) extent. Serial measures of photoreceptor structure by OCT indicated constriction in superior retinal extent within a two-year interval. We conclude that these results should allow early-phase trials of therapy in RHO-adRP to move forward by inclusion of patients with an asymmetric extent of photoreceptor structure and by monitoring therapeutic effects over two years in the superior retina, a reasonable target for subretinal injection.
First Report of a Patient with MPS Type VII, Due to Novel Mutations in GUSB, Who Underwent Enzyme Replacement and Then Hematopoietic Stem Cell Transplantation
Authors: Dubot Patricia , Sabourdy Frédérique , Plat Geneviève , Jubert Charlotte , Cancès Claude , Broué Pierre , Touati Guy , Levade Thierry
Published: October 2019

We report the case of a boy who was diagnosed with mucopolysaccharidosis (MPS) VII at two weeks of age. He harbored three missense β-glucuronidase (GUSB) variations in exon 3: two novel, c.422A>C and c.424C>T, inherited from his mother, and the rather common c.526C>T, inherited from his father. Expression of these variations in transfected HEK293T cells demonstrated that the double mutation c.422A>C;424C>T reduces β-glucuronidase enzyme activity. Enzyme replacement therapy (ERT), using UX003 (vestronidase alfa), was started at four months of age, followed by a hematopoietic stem cell allograft transplantation (HSCT) at 13 months of age. ERT was well tolerated and attenuated visceromegaly and skin infiltration. After a severe skin and gut graft-versus-host disease, ERT was stopped six months after HSCT. The last follow-up examination (at the age of four years) revealed a normal psychomotor development, stabilized growth curve, no hepatosplenomegaly, and no other organ involvement. Intriguingly, enzyme activity had normalized in leukocytes but remained low in plasma. This case report illustrates: (i) The need for an early diagnosis of MPS, and (ii) the possible benefit of a very early enzymatic and/or cellular therapy in this rare form of lysosomal storage disease.
Examination of Adsorption Orientation of Amyloidogenic Peptides Over Nano-Gold Colloidal Particle Surfaces
Authors: Yokoyama Kazushige , Brown Kieran , Shevlin Peter , Jenkins Jack , D’Ambrosio Elizabeth , Ralbovsky Nicole , Battaglia Jessica , Deshmukh Ishan , Ichiki Akane
Published: October 2019

The adsorption of amyloidogenic peptides, amyloid beta 1–40 (Aβ1–40), alpha-synuclein (α-syn), and beta 2 microglobulin (β2m), was attempted over the surface of nano-gold colloidal particles, ranging from d = 10 to 100 nm in diameter (d). The spectroscopic inspection between pH 2 and pH 12 successfully extracted the critical pH point (pHo) at which the color change of the amyloidogenic peptide-coated nano-gold colloids occurred due to aggregation of the nano-gold colloids. The change in surface property caused by the degree of peptide coverage was hypothesized to reflect the ΔpHo, which is the difference in pHo between bare gold colloids and peptide coated gold colloids. The coverage ratio (Θ) for all amyloidogenic peptides over gold colloid of different sizes was extracted by assuming Θ = 0 at ΔpHo = 0. Remarkably, Θ was found to have a nano-gold colloidal size dependence, however, this nano-size dependence was not simply correlated with d. The geometric analysis and simulation of reproducing Θ was conducted by assuming a prolate shape of all amyloidogenic peptides. The simulation concluded that a spiking-out orientation of a prolate was required in order to reproduce the extracted Θ. The involvement of a secondary layer was suggested; this secondary layer was considered to be due to the networking of the peptides. An extracted average distance of networking between adjacent gold colloids supports the binding of peptides as if they are “entangled” and enclosed in an interfacial distance that was found to be approximately 2 nm. The complex nano-size dependence of Θ was explained by available spacing between adjacent prolates. When the secondary layer was formed, Aβ1–40 and α-syn possessed a higher affinity to a partially negative nano-gold colloidal surface. However, β2m peptides tend to interact with each other. This difference was explained by the difference in partial charge distribution over a monomer. Both Aβ1–40 and α-syn are considered to have a partial charge (especially δ+) distribution centering around the prolate axis. The β2m, however, possesses a distorted charge distribution. For a lower Θ (i.e., Θ <0.5), a prolate was assumed to conduct a gyration motion, maintaining the spiking-out orientation to fill in the unoccupied space with a tilting angle ranging between 5° and 58° depending on the nano-scale and peptide coated to the gold colloid.
Melatonin-Induced Transcriptome Variation of Rapeseed Seedlings under Salt Stress
Authors: Tan Xiaoyu , Long Weihua , Zeng Liu , Ding Xiaoyu , Cheng Yong , Zhang Xuekun , Zou Xiling
Published: October 2019

Salt stress inhibits the production of all crop species, including rapeseed (Brassica napus L.), the second most widely planted oil crop species. Although melatonin was confirmed to alleviate salt stress in rapeseed seedlings recently, the mechanism governing the expression levels remains unknown. Therefore, the melatonin-induced transcriptome variation of salt-stressed seedlings was explored. In this study, the transcriptomes of leaves and roots under control (CK), salt (125 mM NaCl, ST) and melatonin (125 mM NaCl plus 50 µM melatonin, MS) treatments were evaluated by using next-generation sequencing techniques. After conducting comparisons of gene expression in the roots and leaves between MS and ST, the differentially expressed gene (DEG) pools were screened. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighted the significant pathways, which were mainly related to plant hormone synthesis and signal transduction, lignin and fatty acid metabolism. The functional genes in the objective KEGG pathways were identified. Furthermore, members of several transcription factor (TF) families participated in the response process. Combined with the hormone (campesterol (CS), jasmonic acid (JA), and gibberellic acid 3 (GA3)) contents measured in the seedlings, it could be concluded that melatonin induced changes in the intrinsic hormone metabolic network, which promoted seedling growth. Thus, this study identified new candidate genes and pathways active during the interactions between melatonin and salt stress, which provide clues for disclosing melatonin’s function in resistance to salt injury. Our results contribute to developing a practical method for sustainable agriculture on saline lands.
Repeated Vaginal Exposures to the Common Cosmetic and Household Preservative Methylisothiazolinone Induce Persistent, Mast Cell-Dependent Genital Pain in ND4 Mice
Authors: Arriaga-Gomez Erica , Kline Jaclyn , Emanuel Elizabeth , Neamonitaki Nefeli , Yangdon Tenzin , Zacheis Hayley , Pasha Dogukan , Lim Jinyoung , Bush Susan , Boo Beebie , Mengistu Hanna , Kinnamon Ruby , Shields-Cutler Robin , Wattenberg Elizabeth , Chatterjea Devavani
Published: October 2019

A history of allergies doubles the risk of vulvodynia—a chronic pain condition of unknown etiology often accompanied by increases in numbers of vulvar mast cells. We previously established the biological plausibility of this relationship in mouse models where repeated exposures to the allergens oxazolone or dinitrofluorobenzene on the labiar skin or inside the vaginal canal of ND4 Swiss Webster outbred mice led to persistent tactile sensitivity and local increases in mast cells. In these models, depletion of mast cells alleviated pain. While exposure to cleaning chemicals has been connected to elevated vulvodynia risk, no single agent has been linked to adverse outcomes. We sensitized female mice to methylisothiazolinone (MI)—a biocide preservative ubiquitous in cosmetics and cleaners—dissolved in saline on their flanks, and subsequently challenged them with MI or saline for ten consecutive days in the vaginal canal. MI-challenged mice developed persistent tactile sensitivity, increased vaginal mast cells and eosinophils, and had higher serum Immunoglobulin E. Therapeutic and preventive intra-vaginal administration of Δ9-tetrahydrocannabinol reduced mast cell accumulation and tactile sensitivity. MI is known to cause skin and airway irritation in humans, and here we provide the first pre-clinical evidence that repeated MI exposures can also provoke allergy-driven genital pain.
The Role of Measurable Residual Disease (MRD) in Hematopoietic Stem Cell Transplantation for Hematological Malignancies Focusing on Acute Leukemia
Authors: Czyz Anna , Nagler Arnon
Published: October 2019

The significance of measurable residual disease (MRD) in hematopoietic stem cell transplantation (HSCT) is well recognized in different hematological malignancies, but the evidence indicate that pre-transplant MRD status is of particular importance in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In ALL, inadequate response at the level of MRD is a commonly accepted risk factor for relapse and thus an indication for allogeneic HSCT. Similarly, growing evidence from the literature strongly suggest that MRD detected by multiparameter flow cytometry or molecular techniques should be also used for risk stratification in AML at the time of HSCT. Despite the well-defined association of MRD and outcomes of HSCT in acute leukemias, there are still many open issues such as the role of additional pre-transplant consolidation for MRD eradication, the ability of HSCT to overcome negative influence of MRD positivity on survival, the impact of conditioning regimen intensity on MRD clearance post HSCT, and transplantation outcomes or the selection of optimal donor with regards to MRD status. In addition, the role of MRD assessment in guiding post-transplant maintenance treatment should also be addressed in prospective trials. These open issues mostly awaiting further clinical studies will be discussed in our current review.
Molecular Links between Central Obesity and Breast Cancer
Authors: Zimta Alina-Andreea , Tigu Adrian Bogdan , Muntean Maximilian , Cenariu Diana , Slaby Ondrej , Berindan-Neagoe Ioana
Published: October 2019

Worldwide, breast cancer (BC) is the most common malignancy in women, in regard to incidence and mortality. In recent years, the negative role of obesity during BC development and progression has been made abundantly clear in several studies. However, the distribution of body fat may be more important to analyze than the overall body weight. In our review of literature, we reported some key findings regarding the role of obesity in BC development, but focused more on central adiposity. Firstly, the adipose microenvironment in obese people bears many similarities with the tumor microenvironment, in respect to associated cellular composition, chronic low-grade inflammation, and high ratio of reactive oxygen species to antioxidants. Secondly, the adipose tissue functions as an endocrine organ, which in obese people produces a high level of tumor-promoting hormones, such as leptin and estrogen, and a low level of the tumor suppressor hormone, adiponectin. As follows, in BC this leads to the activation of oncogenic signaling pathways: NFκB, JAK, STAT3, AKT. Moreover, overall obesity, but especially central obesity, promotes a systemic and local low grade chronic inflammation that further stimulates the increase of tumor-promoting oxidative stress. Lastly, there is a constant exchange of information between BC cells and adipocytes, mediated especially by extracellular vesicles, and which changes the transcription profile of both cell types to an oncogenic one with the help of regulatory non-coding RNAs.
Kinetic Models of Secondary Active Transporters
Authors: Burtscher Verena , Schicker Klaus , Freissmuth Michael , Sandtner Walter
Published: October 2019

Kinetic models have been employed to understand the logic of substrate transport through transporters of the Solute Carrier (SLC) family. All SLC transporters operate according to the alternate access model, which posits that substrate transport occurs in a closed loop of partial reactions (i.e., a transport cycle). Kinetic models can help to find realistic estimates for conformational transitions between individual states of the transport cycle. When constrained by experimental results, kinetic models can faithfully describe the function of a candidate transporter at a pre-steady state. In addition, we show that kinetic models can accurately predict the intra- and extracellular substrate concentrations maintained by the transporter at a steady state, even under the premise of loose coupling between the electrochemical gradient of the driving ion and of the substrate. We define the criteria for the design of a credible kinetic model of the SLC transporter. Parsimony is the guiding principle of kinetic modeling. We argue, however, that the level of acceptable parsimony is limited by the need to account for the substrate gradient established by a secondary active transporter, and for random order binding of co-substrates and substrate. Random order binding has consistently been observed in transporters of the SLC group.
BRAF-Mutated Colorectal Cancer: Clinical and Molecular Insights
Authors: Caputo Francesco , Santini Chiara , Bardasi Camilla , Cerma Krisida , Casadei-Gardini Andrea , Spallanzani Andrea , Andrikou Kalliopi , Cascinu Stefano , Gelsomino Fabio
Published: October 2019

Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. It is a heterogeneous disease, which can be classified into different subtypes, characterized by specific molecular and morphological alterations. In this context, BRAF mutations are found in about 10% of CRC patients and define a particular subtype, characterized by a dismal prognosis, with a median survival of less than 12 months. Chemotherapy plus bevacizumab is the current standard therapy in first-line treatment of BRAF-mutated metastatic CRC (mCRC), with triplet (FOLFOXIRI) plus bevacizumab as a valid option in patients with a good performance status. BRAF inhibitors are not so effective as compared to melanoma, because of various resistance mechanisms. However, the recently published results of the BEACON trial will establish a new standard of care in this setting. This review provides insights into the molecular underpinnings underlying the resistance to standard treatment of BRAF-mutated CRCs, with a focus on their molecular heterogeneity and on the research perspectives both from a translational and a clinical point of view.
Internet of Things Infrastructure for Security and Safety in Public Places
Authors: Chatzimichail Angelos , Chatzigeorgiou Christos , Tsanousa Athina , Ntioudis Dimos , Meditskos Georgios , Andritsopoulos Fotis , Karaberi Christina , Kasnesis Panagiotis , Kogias Dimitrios G. , Gorgogetas Georgios , Vrochidis Stefanos , Patrikakis Charalampos , Kompatsiaris Ioannis
Published: October 2019

We present the technologies and the theoretical background of an intelligent interconnected infrastructure for public security and safety. The innovation of the framework lies in the intelligent combination of devices and human information towards human and situational awareness, so as to provide a protection and security environment for citizens. The framework is currently being used to support visitors in public spaces and events, by creating the appropriate infrastructure to address a set of urgent situations, such as health-related problems and missing children in overcrowded environments, supporting smart links between humans and entities on the basis of goals, and adapting device operation to comply with human objectives, profiles, and privacy. State-of-the-art technologies in the domain of IoT data collection and analytics are combined with localization techniques, ontologies, reasoning mechanisms, and data aggregation in order to acquire a better understanding of the ongoing situation and inform the necessary people and devices to act accordingly. Finally, we present the first results of people localization and the platforms’ ontology and representation framework.
Characterization of Asphalt Mixtures Produced with Coarse and Fine Recycled Asphalt Particles
Authors: Saliani S. Saeed , Carter Alan , Baaj Hassan , Tavassoti Pejoohan
Published: October 2019

Utilizing recycled asphalt pavements (RAP) in pavement construction is known as a sustainable approach with significant economic and environmental benefits. While studying the effect of high RAP contents on the performance of hot mix asphalt (HMA) mixes has been the focus of several research projects, limited work has been done on studying the effect of RAP fraction and particle size on the overall performance of high RAP mixes produced solely with either coarse or fine RAP particles. To this end, three mixes including a conventional control mix with no RAP, a fine RAP mix (FRM) made with 35% percent fine RAP, and a coarse RAP mix (CRM) prepared with 54% of coarse RAP were designed and investigated in this study. These mixes were evaluated with respect to their rutting resistance, fatigue cracking resistance, and low temperature cracking performance. The results indicate that although the CRM had a higher RAP content, it exhibited better or at least the same performance than the FRM. The thermal stress restrained specimen testing (TSRST) results showed that the control mix performed slightly better than the CRM, while the FRM performance was adversely affected with respect to the transition temperature midpoint and the maximum tensile stress temperature. Both of the RAP incorporated mixes exhibited better rutting resistance than the control mix. With regard to fatigue cracking, the CRM performed better than the FRM. It can be concluded that the RAP particle size has a considerable effect on its contribution to the total binder content, the aggregate skeleton of the mix, and ultimately the performance of the mix. In spite of the higher RAP content in the CRM versus FRM, the satisfactory performance observed for the CRM mix indicates a great potential in producing high RAP content mixes through optimizing the RAP particle size and content. The results also suggest that the black curve gradation assumption is not representative of the actual RAP particles contribution in a high RAP mix.
Chronic Kidney Disease: The Silent Epidemy
Authors: Bellasi Antonio , Di Lullo Luca , Di Iorio Biagio
Published: October 2019

Numerous observations suggest that chronic kidney disease (CKD) is an epidemic condition [...]
Non-Invasive Assessment of Metabolic Adaptation in Paediatric Patients Suffering from Type 1 Diabetes Mellitus
Authors: Trefz Phillip , Schmidt Sibylle C. , Sukul Pritam , Schubert Jochen K. , Miekisch Wolfram , Fischer Dagmar-Christiane
Published: October 2019

An analysis of exhaled volatile organic compounds (VOC) may deliver systemic information quicker than available invasive techniques. Metabolic aberrations in pediatric type 1 diabetes (T1DM) are of high clinical importance and could be addressed via breathomics. Real-time breath analysis was combined with continuous glucose monitoring (CGM) and blood tests in children suffering from T1DM and age-matched healthy controls in a highly standardized setting. CGM and breath-resolved VOC analysis were performed every 5 minutes for 9 hours and blood was sampled at pre-defined time points. Per participant (n = 44) food intake and physical activity were identical and a total of 22 blood samples and 93 minutes of breath samples were investigated. The inter-individual variability of glucose, insulin, glucagon, leptin, and soluble leptin receptor relative to food intake differed distinctly between patients and controls. In T1DM patients, the exhaled amounts of acetone, 2-propanol, and pentanal correlated to glucose concentrations. Of note, the strength of these correlations strongly depended on the interval between food intake and breath sampling. Our data suggests that metabolic adaptation through postprandial hyperglycemia and related oxidative stress is immediately reflected in exhaled breath VOC concentrations. Clinical translations of our findings may enable point-of-care applicability of online breath analysis towards personalized medicine.
Three-Dimensional Analysis of Initial Brace Correction in the Setting of Adolescent Idiopathic Scoliosis
Authors: Almansour Haidara , Pepke Wojciech , Bruckner Thomas , Diebo Bassel G. , Akbar Michael
Published: October 2019

The three-dimensional nature of adolescent idiopathic scoliosis (AIS) necessitates a tridimensional assessment and management. Bracing constitutes the mainstay conservative treatment for mild adolescent idiopathic scoliosis. In the literature hitherto, there has been uncertainty regarding the behavior of the spine, pelvis, and vertebral orientations in the context of bracing, especially in the transverse plane. This poses a challenge to healthcare providers, patients, and their families, as brace treatment, although not as invasive as surgery, is laden with medical and psychological complications and could be considered traumatizing. Hence, a thorough understanding of initial three-dimensional spinal behavior in the context of bracing is important. The purpose of this retrospective study was to investigate the immediate 3D impact of Chêneau-type brace. Thirty-eight patients with AIS undergoing Chêneau-type bracing were included. Patients were stratified according to their structural curve topography into thoracic, thoracolumbar, and lumbar groups. 3D reconstruction of the spine using a dedicated biplanar stereoradiography software with and without the brace was performed. The examined anthropometric radiographic measures were pre- to in-brace variations and differences of spinopelvic parameters and vertebral orientations in the coronal, sagittal, and transverse planes. The complex impact of the Chêneau-type brace on different curves in three planes was delineated. In the coronal plane, the Cobb angle was significantly decreased in all types of curves, and the coronal tilt correction was concentrated in specific segments. The impact of the brace in this study on the sagittal profile was variable, including the loss of thoracic kyphosis and lumbar lordosis. In the transverse plane, an axial vertebral rotation change and detorsion above the apex occurred in the thoracolumbar curves. The results from this exploratory study could shed some light on the initial 3D spinal behavior in the context of bracing and may be of beneficial for treating physicians and brace makers.
Microvascular Obstruction in ST-Segment Elevation Myocardial Infarction: Looking Back to Move Forward. Focus on CMR
Authors: Rios-Navarro Cesar , Marcos-Garces Victor , Bayes-Genis Antoni , Husser Oliver , Nuñez Julio , Bodi Vicente
Published: October 2019

After a myocardial infarction (MI), despite the resolution of the coronary occlusion, the deterioration of myocardial perfusion persists in a considerable number of patients. This phenomenon is known as microvascular obstruction (MVO). Initially, the focus was placed on re-establishing blood flow in the epicardial artery. Then, the observation that MVO has profound negative structural and prognostic repercussions revived interest in microcirculation. In the near future, the availability of co-adjuvant therapies (beyond timely coronary reperfusion) aimed at preventing, minimizing, and repairing MVOs and finding convincing answers to questions regarding what, when, how, and where to administer these therapies will be of utmost importance. The objective of this work is to review the state-of-the-art concepts on pathophysiology, diagnostic methods, and structural and clinical implications of MVOs in patients with ST-segment elevation MIs. Based on this knowledge we discuss previously-tested and future opportunities for the prevention and repair of MVO.
Joint Representation and Recognition for Ship-Radiated Noise Based on Multimodal Deep Learning
Authors: Yuan Fei , Ke Xiaoquan , Cheng En
Published: October 2019

Ship recognition based on ship-radiated noise is one of the most important and challenging subjects in underwater acoustic signal processing. The recognition methods for ship-radiated noise recognition include traditional methods and deep learning (DL) methods. Developing from the DL methods and inspired by audio–video speech recognition (AVSR), the paper further introduces multimodal deep learning (multimodal-DL) methods for the recognition of ship-radiated noise. In this paper, ship-radiated noise (acoustics modality) and visual observation of the ships (visual modality) are two different modalities that the multimodal-DL methods model on. The paper specially designs a multimodal-DL framework, the multimodal convolutional neural networks (multimodal-CNNs) for the recognition of ship-radiated noise. Then the paper proposes a strategy based on canonical correlation analysis (CCA-based strategy) to build a joint representation and recognition on the two different single-modality (acoustics modality and visual modality). The multimodal-CNNs and the CCA-based strategy are tested on real ship-radiated noise data recorded. Experimental results show that, using the CCA-based strategy, strong-discriminative information can be built from weak-discriminative information provided from a single-modality. Experimental results also show that as long as any one of the single-modalities can provide information for the recognition, the multimodal-DL methods can have a much better multiclass recognition performance than the DL methods. The paper also discusses the advantages and superiorities of the multimodal-Dl methods over the traditional methods for ship-radiated noise recognition.
Energy and Exergy Analyses of Forced Draft Fan for Marine Steam Propulsion System during Load Change
Authors: Mrzljak Vedran , Blecich Paolo , Anđelić Nikola , Lorencin Ivan
Published: October 2019

A forced draft fan, used for the supply of combustion air into the steam generator of the conventional liquefied natural gas (LNG) carrier was analyzed from the aspect of energy and exergy. The power delivered from the induction motor to the fan was calculated using the manufacturer’s data. The most significant impact on the fan energy power losses is from the air temperature difference between the fan outlet and inlet. The fan energy power losses are inversely proportional to the fan energy efficiency, and the values are between 19.9% and 63.4%, for the entire range of observed steam system loads. The fan exergy destruction depends primarily on the driving power and on the air mass flow rate. At higher loads, an important influence on the fan exergy destruction is from the air pressure at the fan outlet. The exergy efficiency change of the analyzed fan, for the range of observed steam system loads, is directly proportional to the rate of change in the air mass flow, whereas the obtained values of exergy efficiency are between 5.10% and 53.93%. The impact of ambient temperature on the fan exergy destruction and exergy efficiency exhibits is different than in most other steam system components. A change in ambient temperature of 10 °C causes a change in the exergy efficiency of the forced draft fan less than 0.5% in the entire range of observed steam loads.
Pressure Hull Design Methods for Unmanned Underwater Vehicles
Authors: Meschini Alessia , Ridolfi Alessandro , Gelli Jonathan , Pagliai Marco , Rindi Andrea
Published: October 2019

This paper describes design methods for the plastic hull of an Unmanned Underwater Vehicle (UUV), with a particular focus on its cylindrical body and nearly spherical domes at the ends. With the proposed approach, the methodologies reported in the literature were compared, and suitable modifications and improvements were investigated and implemented to extend the classical theories and data to this case study. The investigated underwater vehicle, named FeelHippo, was designed and assembled by the Department of Industrial Engineering of the University of Florence. Its main hull is composed of an extruded PMMA (PolyMethyl MethAcrylate) cylinder and two thermoformed PMMA domes. Breakage of the hull results in destructive phenomena, namely, yielding and buckling. An experimental campaign and FEM (Finite Element Method) analysis were carried out to complete the theoretical study, and the collapse pressures were compared with the derived design values. In conclusion, the proposed innovative method is a lean and effective technique for designing underwater hull domes and predicting the collapse pressures.
Infragravity Wave Energy Partitioning in the Surf Zone in Response to Wind-Sea and Swell Forcing
Authors: Contardo Stephanie , Symonds Graham , Segura Laura , Lowe Ryan , Hansen Jeff
Published: October 2019

An alongshore array of pressure sensors and a cross-shore array of current velocity and pressure sensors were deployed on a barred beach in southwestern Australia to estimate the relative response of edge waves and leaky waves to variable incident wind wave conditions. The strong sea breeze cycle at the study site (wind speeds frequently > 10 m s−1) produced diurnal variations in the peak frequency of the incident waves, with wind sea conditions (periods 2 to 8 s) dominating during the peak of the sea breeze and swell (periods 8 to 20 s) dominating during times of low wind. We observed that edge wave modes and their frequency distribution varied with the frequency of the short-wave forcing (swell or wind-sea) and edge waves were more energetic than leaky waves for the duration of the 10-day experiment. While the total infragravity energy in the surf zone was higher during swell forcing, edge waves were more energetic during wind-sea periods. However, low-frequency (0.005–0.023 Hz) edge waves were found to be dominant in absence of wind-sea conditions, while higher-frequency (0.023–0.050 Hz) edge waves dominated when wind-sea conditions were present.
6-Bromo-N-(2-methyl-2H-benzo[d][1,2,3]triazol-5-yl)quinolin-4-amine
Authors: Asquith Christopher , Tizzard Graham
Published: October 2019

We describe a straightforward synthesis of the title compound, incorporating a relatively rare 2-methyl-2H-1,2,3-triazole heterocylic motif as a potential kinase inhibitor motif. The small molecule crystal structure has been resolved, revealing an interesting packing arrangement and overall conformation. We also performed routine characterization with 1H/13C-NMR and liquid chromatography (LC) and high-resolution mass spectra (HRMS).