bluuebunny/crossref_metadata_2025 huggingface dataset:
A Multi-Mode PDR Perception and Positioning System Assisted by Map Matching and Particle Filtering
Authors: Wang Xuan , Chen Guoliang , Yang Mengyi , Jin Saizhou
Published: February 2020

Currently, pedestrian dead reckoning (PDR) is widely used in indoor positioning. Since there are restrictions on a device’s pose in the procedure of using a smartphone to perform the PDR algorithm, this study proposes a novel heading estimation solution by calculating the integral of acceleration along the direction of the user’s movement. First, a lightweight algorithm, that is, a finite state machine (FSM)-decision tree (DT), is used to monitor and recognize the device mode, and the characteristics of the gyroscope at the corners are used to improve the heading estimate performance during the linear phase. Moreover, to solve the problem of heading angle deviation accumulation on positioning, a map-aided particle filter (PF) and behavior perception techniques are introduced to constrain the heading and correct the trajectory through the wall after filtering. The results indicate that the recognition of phone pose can be 93.25%. The improved heading estimation method can achieve higher stability and accuracy than the traditional step-wise method. The localization error can reduce to approximately 2.2 m when the smartphone is held at certain orientations.
High Diagnostic Accuracy of RT-QuIC Assay in a Prospective Study of Patients with Suspected sCJD
Authors: Fiorini Michele , Iselle Giorgia , Perra Daniela , Bongianni Matilde , Capaldi Stefano , Sacchetto Luca , Ferrari Sergio , Mombello Aldo , Vascellari Sarah , Testi Silvia , Monaco Salvatore , Zanusso Gianluigi
Published: February 2020

The early and accurate in vivo diagnosis of sporadic Creutzfeldt–Jakob disease (sCJD) is essential in order to differentiate CJD from treatable rapidly progressive dementias. Diagnostic investigations supportive of clinical CJD diagnosis include magnetic resonance imaging (MRI), electroencephalogram (EEG), 14-3-3 protein detection, and/or real-time quaking-induced conversion (RT-QuIC) assay positivity in the cerebrospinal fluid (CSF) or in other tissues. The total CSF tau protein concentration has also been used in a clinical setting for improving the CJD diagnostic sensitivity and specificity. We analyzed 182 CSF samples and 42 olfactory mucosa (OM) brushings from patients suspected of having sCJD with rapidly progressive dementia (RPD), in order to determine the diagnostic accuracy of 14-3-3, the total tau protein, and the RT-QuIC assay. A probable and definite sCJD diagnosis was assessed in 102 patients. The RT-QuIC assay on the CSF samples showed a 100% specificity and a 96% sensitivity, significantly higher compared with 14-3-3 (84% sensitivity and 46% specificity) and tau (85% sensitivity and 70% specificity); however, the combination of RT-QuIC testing of the CSF and OM samples resulted in 100% sensitivity and specificity, proving a significantly higher accuracy of RT-QuIC compared with the surrogate biomarkers in the diagnostic setting of patients with RPD. Moreover, we showed that CSF blood contamination or high protein levels might interfere with RT-QuIC seeding. In conclusion, we provided further evidence that the inclusion of an RT-QuIC assay of the CSF and OM in the diagnostic criteria for sCJD has radically changed the clinical approach towards the diagnosis.
Nitric Oxide and Hydrogen Peroxide Signaling in Extractive Shiraia Fermentation by Triton X-100 for Hypocrellin A Production
Authors: Li Xin Ping , Wang Yue , Ma Yan Jun , Wang Jian Wen , Zheng Li Ping
Published: February 2020

Shiraia mycelial culture is a promising biotechnological alternative for the production of hypocrellin A (HA), a new photosensitizer for anticancer photodynamic therapy (PDT). The extractive fermentation of intracellular HA in the nonionic surfactant Triton X-100 (TX100) aqueous solution was studied in the present work. The addition of 25 g/L TX100 at 36 h of the fermentation not only enhanced HA exudation to the broth by 15.6-fold, but stimulated HA content in mycelia by 5.1-fold, leading to the higher production 206.2 mg/L, a 5.4-fold of the control on day 9. After the induced cell membrane permeabilization by TX100 addition, a rapid generation of nitric oxide (NO) and hydrogen peroxide (H2O2) was observed. The increase of NO level was suppressed by the scavenger vitamin C (VC) of reactive oxygen species (ROS), whereas the induced H2O2 production could not be prevented by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), suggesting that NO production may occur downstream of ROS in the extractive fermentation. Both NO and H2O2 were proved to be involved in the expressions of HA biosynthetic genes (Mono, PKS and Omef) and HA production. NO was found to be able to up-regulate the expression of transporter genes (MFS and ABC) for HA exudation. Our results indicated the integrated role of NO and ROS in the extractive fermentation and provided a practical biotechnological process for HA production.
Lipidated Analogs of the LL-37-Derived Peptide Fragment KR12—Structural Analysis, Surface-Active Properties and Antimicrobial Activity
Authors: Kamysz Elżbieta , Sikorska Emilia , Jaśkiewicz Maciej , Bauer Marta , Neubauer Damian , Bartoszewska Sylwia , Barańska-Rybak Wioletta , Kamysz Wojciech
Published: February 2020

An increasing number of multidrug-resistant pathogens is a serious problem of modern medicine and new antibiotics are highly demanded. In this study, different n-alkyl acids (C2-C14) and aromatic acids (benzoic and trans-cinnamic) were conjugated to the N-terminus of KR12 amide. The effect of this modification on antimicrobial activity (ESKAPE bacteria and biofilm of Staphylococcus aureus) and cytotoxicity (human red blood cells and HaCaT cell line) was examined. The effect of lipophilic modifications on helicity was studied by CD spectroscopy, whereas peptide self-assembly was studied by surface tension measurements and NMR spectroscopy. As shown, conjugation of the KR12-NH2 peptide with C4-C14 fatty acid chains enhanced the antimicrobial activity with an optimum demonstrated by C8-KR12-NH2 (MIC 1–4 μg/mL against ESKAPE strains; MBEC of S. aureus 4–16 μg/mL). Correlation between antimicrobial activity and self-assembly behavior of C14-KR12-NH2 and C8-KR12-NH2 has shown that the former self-assembled into larger aggregated structures, which reduced its antimicrobial activity. In conclusion, N-terminal modification can enhance antimicrobial activity of KR12-NH2; however, at the same time, the cytotoxicity increases. It seems that the selectivity against pathogens over human cells can be achieved through conjugation of peptide N-terminus with appropriate n-alkyl fatty and aromatic acids.
Human Tyrosinase: Temperature-Dependent Kinetics of Oxidase Activity
Authors: Young Kenneth L. , Kassouf Claudia , Dolinska Monika B. , Anderson David Eric , Sergeev Yuri V.
Published: February 2020

Human tyrosinase (Tyr) is involved in pigment biosynthesis, where mutations in its corresponding gene TYR have been linked to oculocutaneous albinism 1, an autosomal recessive disorder. Although the enzymatic capabilities of Tyr have been well-characterized, the thermodynamic driving forces underlying melanogenesis remain unknown. Here, we analyze protein binding using the diphenol oxidase behavior of Tyr and van ’t Hoff temperature-dependent analysis. Recombinant Tyr was expressed and purified using a combination of affinity and size-exclusion chromatography. Michaelis-Menten constants were measured spectrophotometrically from diphenol oxidase reactions of Tyr, using L-3,4-dihydroxyphenylalanine (L-DOPA) as a substrate, at temperatures: 25, 31, 37, and 43 °C. Under the same conditions, the Tyr structure and the L-DOPA binding activity were simulated using 3 ns molecular dynamics and docking. The thermal Michaelis-Menten kinetics data were subjected to the van ‘t Hoff analysis and fitted with the computational model. The temperature-dependent analysis suggests that the association of L-DOPA with Tyr is a spontaneous enthalpy-driven reaction, which becomes unfavorable at the final step of dopachrome formation.
Assessment of a 18F-Phenylboronic Acid Radiotracer for Imaging Boron in Maize
Authors: Housh Alexandra B. , Matthes Michaela S. , Gerheart Amber , Wilder Stacy L. , Kil Kun-Eek , Schueller Michael , Guthrie James M. , McSteen Paula , Ferrieri Richard
Published: February 2020

Boron (B) is an essential plant micronutrient. Deficiencies of B have drastic consequences on plant development leading to crop yield losses and reductions in root and shoot growth. Understanding the molecular and cellular consequences of B deficiency is challenging, partly because of the limited availability of B imaging techniques. In this report we demonstrate the efficacy of using 4-fluorophenylboronic acid (FPBA) as a B imaging agent, which is a derivative of the B deficiency mimic phenylboronic acid (PBA). We show that radioactively labelled [18F]FPBA (t½=110 m) accumulates at the root tip, the root elongation zone and at lateral root initiation sites in maize roots, and also translocates to the shoot where it accumulates along the leaf edges. Treatment of maize seedlings using FPBA and PBA causes a shortened primary root phenotype with absence of lateral roots in a dose-dependent manner. The primary root defects can be partially rescued by the addition of boric acid indicating that PBA can be used to induce B deficiency in maize and that radioactively labelled FPBA can be used to image sites of B demand on a tissue level.
Modulation of AMPA Receptors by Nitric Oxide in Nerve Cells
Authors: Ivanova Violetta O. , Balaban Pavel M. , Bal Natalia V.
Published: February 2020

Nitric oxide (NO) is a gaseous molecule with a large number of functions in living tissue. In the brain, NO participates in numerous intracellular mechanisms, including synaptic plasticity and cell homeostasis. NO elicits synaptic changes both through various multi-chain cascades and through direct nitrosylation of targeted proteins. Along with the N-methyl-d-aspartate (NMDA) glutamate receptors, one of the key components in synaptic functioning are α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors—the main target for long-term modifications of synaptic effectivity. AMPA receptors have been shown to participate in most of the functions important for neuronal activity, including memory formation. Interactions of NO and AMPA receptors were observed in important phenomena, such as glutamatergic excitotoxicity in retinal cells, synaptic plasticity, and neuropathologies. This review focuses on existing findings that concern pathways by which NO interacts with AMPA receptors, influences properties of different subunits of AMPA receptors, and regulates the receptors’ surface expression.
Engineering Biology to Construct Microbial Chassis for the Production of Difficult-to-Express Proteins
Authors: Kim Kangsan , Choe Donghui , Lee Dae-Hee , Cho Byung-Kwan
Published: February 2020

A large proportion of the recombinant proteins manufactured today rely on microbe-based expression systems owing to their relatively simple and cost-effective production schemes. However, several issues in microbial protein expression, including formation of insoluble aggregates, low protein yield, and cell death are still highly recursive and tricky to optimize. These obstacles are usually rooted in the metabolic capacity of the expression host, limitation of cellular translational machineries, or genetic instability. To this end, several microbial strains having precisely designed genomes have been suggested as a way around the recurrent problems in recombinant protein expression. Already, a growing number of prokaryotic chassis strains have been genome-streamlined to attain superior cellular fitness, recombinant protein yield, and stability of the exogenous expression pathways. In this review, we outline challenges associated with heterologous protein expression, some examples of microbial chassis engineered for the production of recombinant proteins, and emerging tools to optimize the expression of heterologous proteins. In particular, we discuss the synthetic biology approaches to design and build and test genome-reduced microbial chassis that carry desirable characteristics for heterologous protein expression.
Antidiabetic Effects of Bisamide Derivative of Dicarboxylic Acid in Metabolic Disorders
Authors: Pakhomova Angelina Vladimirovna , Nebolsin Vladimir Evgenievich , Pershina Olga Victorovna , Krupin Vyacheslav Andreevich , Sandrikina Lubov Alexandrovna , Pan Edgar Sergeevich , Ermakova Natalia Nicolaevna , Vaizova Olga Evgenevna , Widera Darius , Grimm Wolf-Dieter , Kravtsov Viacheslav Yur’evich , Afanasiev Sergey Alexandrovich , Morozov Sergey Georgievich , Kubatiev Aslan Amirkhanovich , Dygai Alexander Mikhaylovich , Skurikhin Evgenii Germanovich
Published: February 2020

In clinical practice, the metabolic syndrome can lead to multiple complications, including diabetes. It remains unclear which component of the metabolic syndrome (obesity, inflammation, hyperglycemia, or insulin resistance) has the strongest inhibitory effect on stem cells involved in beta cell regeneration. This makes it challenging to develop effective treatment options for complications such as diabetes. In our study, experiments were performed on male C57BL/6 mice where metabolic disorders have been introduced experimentally by a combination of streptozotocin-treatment and a high-fat diet. We evaluated the biological effects of Bisamide Derivative of Dicarboxylic Acid (BDDA) and its impact on pancreatic stem cells in vivo. To assess the impact of BDDA, we applied a combination of histological and biochemical methods along with a cytometric analysis of stem cell and progenitor cell markers. We show that in mice with metabolic disorders, BDDA has a positive effect on lipid and glucose metabolism. The pancreatic restoration was associated with a decrease of the inhibitory effects of inflammation and obesity factors on pancreatic stem cells. Our data shows that BDDA increases the number of pancreatic stem cells. Thus, BDDA could be used as a new compound for treating complication of the metabolic syndrome such as diabetes.
Role of Gangliosides in Peripheral Pain Mechanisms
Authors: Sántha Péter , Dobos Ildikó , Kis Gyöngyi , Jancsó Gábor
Published: February 2020

Gangliosides are abundantly occurring sialylated glycosphingolipids serving diverse functions in the nervous system. Membrane-localized gangliosides are important components of lipid microdomains (rafts) which determine the distribution of and the interaction among specific membrane proteins. Different classes of gangliosides are expressed in nociceptive primary sensory neurons involved in the transmission of nerve impulses evoked by noxious mechanical, thermal, and chemical stimuli. Gangliosides, in particular GM1, have been shown to participate in the regulation of the function of ion channels, such as transient receptor potential vanilloid type 1 (TRPV1), a molecular integrator of noxious stimuli of distinct nature. Gangliosides may influence nociceptive functions through their association with lipid rafts participating in the organization of functional assemblies of specific nociceptive ion channels with neurotrophins, membrane receptors, and intracellular signaling pathways. Genetic and experimentally induced alterations in the expression and/or metabolism of distinct ganglioside species are involved in pathologies associated with nerve injuries, neuropathic, and inflammatory pain in both men and animals. Genetic and/or pharmacological manipulation of neuronal ganglioside expression, metabolism, and action may offer a novel approach to understanding and management of pain.
Coreference Resolution: Toward End-to-End and Cross-Lingual Systems
Authors: Ferreira Cruz André , Rocha Gil , Lopes Cardoso Henrique
Published: February 2020

The task of coreference resolution has attracted considerable attention in the literature due to its importance in deep language understanding and its potential as a subtask in a variety of complex natural language processing problems. In this study, we outlined the field’s terminology, describe existing metrics, their differences and shortcomings, as well as the available corpora and external resources. We analyzed existing state-of-the-art models and approaches, and reviewed recent advances and trends in the field, namely end-to-end systems that jointly model different subtasks of coreference resolution, and cross-lingual systems that aim to overcome the challenges of less-resourced languages. Finally, we discussed the main challenges and open issues faced by coreference resolution systems.
Aedes aegypti (Diptera: Culicidae) Immune Responses with Different Feeding Regimes Following Infection by the Entomopathogenic Fungus Metarhizium anisopliae
Authors: Cabral Sara , de Paula Adriano , Samuels Richard , da Fonseca Rodrigo , Gomes Simone , Silva José Roberto , Mury Flávia
Published: February 2020

The mosquito Aedes aegypti is the most notorious vector of illness-causing viruses. The use of entomopathogenic fungi as bioinsecticides is a promising alternative for the development of novel mosquito control strategies. We investigate whether differences in immune responses could be responsible for modifications in survival rates of insects following different feeding regimes. Sucrose and blood-fed adult A. aegypti females were sprayed with M. anisopliae 1 × 106 conidia mL−1, and after 48 h, the midgut and fat body were dissected. We used RT-qPCR to monitor the expression of Cactus and REL1 (Toll pathway), IMD, REL2, and Caspar (IMD pathway), STAT and PIAS (JAK-STAT pathway), as well as the expression of antimicrobial peptides (Defensin A, Attacin and Cecropin G). REL1 and REL2 expression in both the midgut and fat body were higher in blood-fed fungus-challenged A. aegypti than in sucrose-fed counterparts. Interestingly, infection of sucrose-fed insects induced Cactus expression in the fat body, a negative regulator of the Toll pathway. The IMD gene was upregulated in the fat body in response to fungal infection after a blood meal. Additionally, we observed the induction of antimicrobial peptides in the blood-fed fungus-challenged insects. This study suggests that blood-fed A. aegypti are less susceptible to fungal infection due to the rapid induction of Toll and IMD immune pathways.
Predation Pressure on Sentinel Insect Prey along a Riverside Urbanization Gradient in Hungary
Authors: Eötvös Csaba Béla , Lövei Gábor L. , Magura Tibor
Published: February 2020

Urbanization is one of the most important global trends which causes habitat reduction and alteration which are, in turn, the main reasons for the well-documented reduction in structural and functional diversity in urbanized environments. In contrast, effects on ecological mechanisms are less known. Predation is one of the most important ecological functions because of its community-structuring effects. We studied six forest habitats along a riverside urbanization gradient in Szeged, a major city in southern Hungary, crossed by the river Tisza, to describe how extreme events (e.g., floods) as primary selective pressure act on adaptation in riparian habitats. We found a generally decreasing predation pressure from rural to urban habitats as predicted by the increasing disturbance hypothesis (higher predator abundances in rural than in urban habitats). The only predators that reacted differently to urbanization were ground active arthropods, where results conformed to the prediction of the intermediate disturbance hypothesis (higher abundance in moderately disturbed suburban habitats). We did not find any evidence that communities exposed to extreme flood events were preadapted to the effects of urbanization. The probable reason is that changes accompanied by urbanization are much faster than natural landscape change, so the communities cannot adapt to them.
Polyphenol-Rich Purple Corn Pericarp Extract Adversely Impacts Herbivore Growth and Development
Authors: Tayal Mandeep , Somavat Pavel , Rodriguez Isabella , Thomas Tina , Christoffersen Bradley , Kariyat Rupesh
Published: February 2020

Plant secondary metabolites such as terpenes, phenolics, glycosides, and alkaloids play various functional roles including pigmentation, foliar and floral volatile synthesis, hormonal regulation, and direct and indirect defenses. Among these, phenolic compounds are commonly found in plants, but vary in the distribution of their specific compounds among plant families. Polyphenols, including anthocyanins and tannins, are widely distributed and have been well documented for their roles- primarily in plant pigmentation and also in plant defenses. However, commercialization of such compounds for use in insect pest management is severely hampered by expensive, inefficient, and time-consuming extraction protocols. Using a recently developed inexpensive and easy extraction method using the byproducts of pigmented (purple) corn processing, we examined whether the crude pericarp extract rich in polyphenols can affect the growth and development of tobacco hornworm (Manduca sexta L.) caterpillars. Our findings show that purple corn pericarp extract negatively affected M. sexta egg hatching and larval mass gain and prolonged developmental time compared to regular yellow corn extract or an artificial control diet. We also found that these effects were more severe during the early stages of caterpillar development. These results conclusively demonstrate that purple corn pericarp, an inexpensive by-product of the corn milling industry, is a valuable product with excellent potential as an insect antifeedant.
Suitability of Semolina, Cracked Wheat and Cracked Maize as Feeding Commodities for Tribolium castaneum (Herbst; Coleoptera: Tenebrionidae)
Authors: Skourti Anna , Kavallieratos Nickolas G. , Papanikolaou Nikos E.
Published: February 2020

In the current study it was investigated the suitability of semolina, cracked wheat and cracked maize as feeding commodities for the red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae). The pest completed its development on all tested commodities. The developmental time of larvae was lower on cracked wheat (59.6 days) and cracked maize (54.6 days) compared to semolina (72.8 days). The developmental time of pupae did not differ significantly among tested commodities, ranging from 6.2 to 6.6 days. Female and male longevities were 70.9 and 77.1 days, 92.2 and 77.9 days and 177.0 and 183.7 days, when T. castaneum was fed on semolina, cracked wheat and cracked maize, respectively. The highest fecundity (28.7 eggs/female) was recorded when T. castaneum was fed on semolina, followed by cracked wheat (2.7 eggs/female) and cracked maize (1.2 eggs/female). The prolonged adult longevity, which was observed on cracked maize, may be attributed to the absence of the cost of reproduction, due to low fecundity on this commodity. The values of the intrinsic rate of increase were 0.014 and −0.021 females/female/day when it was fed on semolina and cracked wheat, respectively, while no demographic analysis was carried out for cracked maize due to high early larval mortality and low fecundity on this commodity. The net reproductive rate and mean generation time were 6.19 females/female and 127.5 days and 0.16 females/female and 91.9 days, when it was fed on semolina and cracked wheat, respectively. Based on demographic analysis, T. castaneum population growth is favored only on semolina. We expect semolina to act as a suitable commodity for T. castaneum, while cracked wheat and cracked maize allow only its survival by acting as alternative commodities. The estimated demographic parameters of T. castaneum on the tested commodities could be used as a useful tool to predict its population outcome in storage facilities.
A Guild-Based Protocol to Target Potential Natural Enemies of Philaenus spumarius (Hemiptera: Aphrophoridae), a Vector of Xylella fastidiosa (Xanthomonadaceae): A Case Study with Spiders in the Olive Grove
Authors: Benhadi-Marín Jacinto , Villa María , Pereira Luís F. , Rodrigues Isabel , Morente Marina , Baptista Paula , Pereira José Alberto
Published: February 2020

The olive grove is a key landscape across the Mediterranean basin. This agroecosystem is threatened by Xylella fastidiosa, the causal agent of the olive tree quick decline syndrome, Philaenus spumarius being the main vector. A way to limit pest populations relies on the use of biological control agents such as arthropods. Among them, spiders are generalist predators with different hunting strategies that feed mostly on insects and can contribute to limit pests. In this work, field and laboratory data were used to provide a protocol aiming to facilitate the selection of species of spiders among different guilds that could represent potential natural enemies of P. spumarius. Sampling of spiders was conducted in olive groves in northeastern Portugal. Two species, namely the orb-weaver Araniella cucurbitina and the ambusher Synema globosum, were selected according to the dominant guilds of spiders inhabiting the olive crop. We tested the differences of potential predatory efficiency using classical functional response tests with P. spumarius as prey. A type-II functional response was found for A. cucurbitina, whereas a type-I response was found for S. globosum. This difference uncovers a different potential efficiency among the two species as natural enemies of P. spumarius with relevant implications at high prey density in the field. A conceptual workflow to follow the fieldwork and selection of species for further work (i.e., laboratory assays) is provided and discussed. Standardized methods regarding the assessment of the suitability and efficiency of potential natural enemies are essential for the integration of results at different geographical extents and crops. Selecting functional counterparts such as different species of predators occurring at different locations that use the same prey (e.g., a pest) in the same way (e.g., hunting strategy) would facilitate developing biological control schemes.
Prognostic Factors for Iatrogenic Tracheal Rupture: A Single-Center Retrospective Cohort Study
Authors: Krämer Sebastian , Broschewitz Johannes , Kirsten Holger , Sell Carolin , Eichfeld Uwe , Struck Manuel Florian
Published: February 2020

Iatrogenic tracheal ruptures are rare but severe complications of medical interventions. The main goal of this study was to explore prognostic factors for all-cause mortality and rupture-related (adjusted) mortality. We retrospectively analyzed patients admitted to an academic referral center over a 15-year period (2004–2018). Fifty-four patients met the inclusion criteria, of whom 36 patients underwent surgical repair and 18 patients were treated conservatively. In a 90-day follow-up, the all-cause mortality was 50%, while the adjusted mortality was 13%. Rupture length was identified as a predictor for all-cause mortality (area under the curve, 0.84; 95% confidence interval (CI) 0.74–0.94) with a cutoff rupture length of 4.5 cm (sensitivity, 0.70; specificity, 0.81). Multivariate analysis confirmed rupture length as a prognostic factor for all-cause mortality (adjusted hazard ratio (HR) 1.5; 95% CI 1.2–1.9; p = 0.001), but not for adjusted mortality (HR 1.5; 95% CI 0.97–2.3; p = 0.068), while mediastinitis predicted adjusted mortality (HR 5.8; 95% CI 1.1–31.7; p = 0.042), but not all-cause mortality (HR 1.6; 95% CI 0.7–3.5; p = 0.243). The extent of iatrogenic tracheal rupture and mediastinitis might be relevant prognostic factors for all-cause mortality and adjusted mortality, respectively.
Neoadjuvant Chemoradiotherapy and Larynx-Preserving Surgery for Cervical Esophageal Cancer
Authors: Dai Kun-Yao , Yu Yu-Chao , Leu Yi-Shing , Chi Chih-Wen , Chan Mei-Lin , Tsai Chung-Hsin , Lin Huan-Chau , Huang Wen-Chien , Chen Yu-Jen
Published: February 2020

Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is widely used for treating locally advanced esophageal cancer in the thorax. This study evaluated the feasibility of neoadjuvant CCRT as a larynx preservation strategy for treating cervical esophageal squamous cell carcinoma (SCC) by a multidisciplinary team. Fifteen patients with cervical esophageal SCC who received neoadjuvant CCRT and radical surgery at our institution were reviewed. All patients received CCRT using the intensity-modulated radiation therapy with 48 Gy to gross tumor and 43.2 Gy to regional lymphatic basin in 24 fractions. Side effects, clinical tumor responses, pathological responses, and surgical margin status were analyzed. Pathological T down-staging was noted in seven patients (46.7%); pathological complete response was achieved in three patients (20%). Fourteen patients (93.3%) had larynx preservation; eight patients (53.3%) achieved negative surgical margins. The 2-year overall survival, local relapse-free survival, and regional relapse-free survival were 50.6%, 62.2%, and 47.5%, respectively. Neoadjuvant CCRT and larynx-sparing surgery are feasible and tolerable in patients with cervical esophageal SCC. Prospectively designed studies for large patient groups and long-term follow-up results are needed for validating this multimodality therapy.
Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak
Authors: Zhao Shi , Musa Salihu S. , Lin Qianying , Ran Jinjun , Yang Guangpu , Wang Weiming , Lou Yijun , Yang Lin , Gao Daozhou , He Daihai , Wang Maggie H.
Published: February 2020

Background: In December 2019, an outbreak of respiratory illness caused by a novel coronavirus (2019-nCoV) emerged in Wuhan, China and has swiftly spread to other parts of China and a number of foreign countries. The 2019-nCoV cases might have been under-reported roughly from 1 to 15 January 2020, and thus we estimated the number of unreported cases and the basic reproduction number, R0, of 2019-nCoV. Methods: We modelled the epidemic curve of 2019-nCoV cases, in mainland China from 1 December 2019 to 24 January 2020 through the exponential growth. The number of unreported cases was determined by the maximum likelihood estimation. We used the serial intervals (SI) of infection caused by two other well-known coronaviruses (CoV), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) CoVs, as approximations of the unknown SI for 2019-nCoV to estimate R0. Results: We confirmed that the initial growth phase followed an exponential growth pattern. The under-reporting was likely to have resulted in 469 (95% CI: 403–540) unreported cases from 1 to 15 January 2020. The reporting rate after 17 January 2020 was likely to have increased 21-fold (95% CI: 18–25) in comparison to the situation from 1 to 17 January 2020 on average. We estimated the R0 of 2019-nCoV at 2.56 (95% CI: 2.49–2.63). Conclusion: The under-reporting was likely to have occurred during the first half of January 2020 and should be considered in future investigation.
Brain Pathology in Mucopolysaccharidoses (MPS) Patients with Neurological Forms
Authors: Viana Gustavo M. , Priestman David A. , Platt Frances M. , Khan Shaukat , Tomatsu Shunji , Pshezhetsky Alexey V.
Published: February 2020

Mucopolysaccharidoses (MPS) are the group of lysosomal storage disorders caused by deficiencies of enzymes involved in the stepwise degradation of glycosaminoglycans. To identify brain pathology common for neurological MPS, we conducted a comprehensive analysis of brain cortex tissues from post-mortem autopsy materials of eight patients affected with MPS I, II, IIIA, IIIC, and IIID, and age-matched controls. Frozen brain tissues were analyzed for the abundance of glycosaminoglycans (heparan, dermatan, and keratan sulfates) by LC-MS/MS, glycosphingolipids by normal phase HPLC, and presence of inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor superfamily member 10 (TNFSF10) by Western blotting. Fixed tissues were stained for the markers for microgliosis, astrogliosis, misfolded proteins, impaired autophagy, and GM2 ganglioside. Our results demonstrate that increase of heparan sulfate, decrease of keratan sulfate, and storage of simple monosialogangliosides 2 and 3 (GM2 and GM3) as well as the neutral glycosphingolipid, LacCer, together with neuroinflammation and neuronal accumulation of misfolded proteins are the hallmarks of brain pathology in MPS patients. These biomarkers are similar to those reported in the corresponding mouse models, suggesting that the pathological mechanism is common for all neurological MPS in humans and mice.
Influence of Serum Vitamin D Level in the Response of Actinic Keratosis to Photodynamic Therapy with Methylaminolevulinate
Authors: Moreno Ricardo , Nájera Laura , Mascaraque Marta , Juarranz Ángeles , González Salvador , Gilaberte Yolanda
Published: February 2020

In mouse models of squamous cell carcinoma, pre-treatment with calcitriol prior to photodynamic therapy with aminolevulinic acid (ALA) enhances tumor cell death. We have evaluated the association between vitamin D status and the response of actinic keratoses to photodynamic therapy with methylaminolevulinate. Twenty-five patients with actinic keratoses on the head received one session of photodynamic therapy with methylaminolevulinate. Biopsies were taken at baseline and six weeks after treatment. Immuno-histochemical staining was performed for VDR, P53, Ki67 and β-catenin. Basal serum 25(OH)D levels were determined. Cases with a positive histological response to treatment had significantly higher serum 25(OH)D levels (26.96 (SD 7.49) ngr/mL) than those without response (18.60 (SE 7.49) ngr/mL) (p = 0.05). Patients with a complete clinical response displayed lower basal VDR expression (35.71% (SD 19.88)) than partial responders (62.78% (SD 16.735)), (p = 0.002). Our results support a relationship between vitamin D status and the response of actinic keratoses to photodynamic therapy with methylaminolevulinate.
Role of Endothelial ADAM17 in Early Vascular Changes Associated with Diabetic Retinopathy
Authors: Shalaby Lamiaa , Thounaojam Menaka , Tawfik Amany , Li Junnan , Hussein Khaled , Jahng Wan Jin , Al-Shabrawey Mohamed , Kwok Hang Fai , Bartoli Manuela , Gutsaeva Diana
Published: February 2020

ADAM17, a disintegrin and metalloproteinase 17, is a transmembrane metalloproteinase that regulates bioavailability of multiple membrane-bound proteins via ectodomain shedding. ADAM17 activity was shown to contribute to a number of vascular pathologies, but its role in the context of diabetic retinopathy (DR) is not determined. We found that expression and enzymatic activity of ADAM17 are upregulated in human diabetic postmortem retinas and a mouse model of streptozotocin-induced diabetes. To further investigate the contribution of ADAM17 to vascular alterations associated with DR, we used human retinal endothelial cells (HREC) treated with ADAM17 neutralizing antibodies and exposed to glucidic stress and streptozotocin-induced endothelial ADAM17 knockout mice. Evaluation of vascular permeability, vascular inflammation, and oxidative stress was performed. Loss of ADAM17 in endothelial cells markedly reduced oxidative stress evidenced by decreased levels of superoxide, 3-nitrotyrosine, and 4-hydroxynonenal and decreased leukocyte-endothelium adhesive interactions in vivo and in vitro. Reduced leukostasis was associated with decreased vascular permeability and was accompanied by downregulation of intercellular adhesion molecule-1 expression. Reduction in oxidative stress in HREC was associated with downregulation of NAD(P)H oxidase 4 (Nox4) expression. Our data suggest a role for endothelial ADAM17 in DR pathogenesis and identify ADAM17 as a potential new therapeutic target for DR.
Pulmonary Vein Enlargement as an Independent Predictor for New-Onset Atrial Fibrillation
Authors: Kim Sunwon , Kim Yong-Hyun , Lee Seung-Hwa , Kim Jin-Seok
Published: February 2020

Pulmonary vein (PV) enlargement is associated with atrial fibrillation (AF). However, the predictive value of PV volume for new-onset AF has not been determined. We retrospectively assessed and enrolled non-AF subjects who underwent echocardiography and cardiac CT angiography (CCTA) around the same time and evaluated the development of AF longitudinally. PV volume was assessed by estimating the three-dimensional CCTA-derived mid-diastolic PV volume from the ostium to tertiary branches. Overall, 1105 subjects were enrolled. Among them, 29 developed AF during a mean follow-up of 4.28 ± 3.08 years after baseline CCTA and echocardiography. The AF group had a higher proportion of older aged subjects, a higher ratio of early mitral flow velocity (E) to early mitral annular tissue velocity (Em), higher Em, and larger left atrial (LAVI) and PV (PVVI) volume indices. PVVI was independently associated with male sex, left ventricular dimension, E/Em and LAVI. AF incidence increased markedly across each baseline PVVI tertile (2.2%, 5.1%, and 10.8%). In the multivariate Cox model, increased PVVI was independently associated with new-onset AF (hazard ratio (HR) = 5.401, 4.931–6.193, p = 0.007). Based on the analysis of multimodal cardiac imaging, our results provide mechanistic insights into PV remodeling and its potential role as a link between diastolic dysfunction and developing AF.
Diagnosis and Management of Non-Variceal Gastrointestinal Hemorrhage: A Review of Current Guidelines and Future Perspectives
Authors: Mujtaba Sobia , Chawla Saurabh , Massaad Julia Fayez
Published: February 2020

Non-variceal gastrointestinal bleeding (GIB) is a significant cause of mortality and morbidity worldwide which is encountered in the ambulatory and hospital settings. Hemorrhage form the gastrointestinal (GI) tract is categorized as upper GIB, small bowel bleeding (also formerly referred to as obscure GIB) or lower GIB. Although the etiologies of GIB are variable, a strong, consistent risk factor is use of non-steroidal anti-inflammatory drugs. Advances in the endoscopic diagnosis and treatment of GIB have led to improved outcomes. We present an updated review of the current practices regarding the diagnosis and management of non-variceal GIB, and possible future directions.
Use of Bimodal Particle Size Distribution in Selective Laser Melting of 316L Stainless Steel
Authors: Coe Hannah G. , Pasebani Somayeh
Published: February 2020

Spherical powders with single-mode (D50 = 36.31 µm), and bimodal (D50,L = 36.31 µm, D50,s = 5.52 µm) particle size distribution were used in selective laser melting of 316L stainless steel in nitrogen atmosphere at volumetric energy densities ranging from 35.7–116.0 J/mm3. Bimodal particle size distribution could provide up to 2% greater tap density than single-mode powder. For low laser power (107–178 W), where relative density was <99%, bimodal feedstock resulted in higher density than single-mode feedstock. However, at higher power (>203 W), the density of bimodal-fed components decreased as the energy density increased due to vaporizing of the fine powder in bimodal distributions. Size of intergranular cell regions did not appear to vary significantly between single-mode and bimodal specimens (0.394–0.531 µm2 at 81–116 J/mm3). Despite higher packing densities in powder feedstock with bimodal particle size distribution, the results of this study suggest that differences in conduction melting and vaporization points between the two primary particle sizes would limit the maximum achievable density of additively manufactured components produced from bimodal powder size distribution.
Development of a Position Measuring Device of a Deep-Sea Pipeline Based on Flange Center Positioning
Authors: Wang Zhuo , Dang Hong-xing , Wang Tao , Zhang Bo
Published: February 2020

A deep-sea pipeline position and attitude-measuring device based on pipeline outer circle positioning can measure the spatial relative positions of the end faces of two oil pipelines in the deep sea. This device can provide the necessary data to make a transition pipeline connecting two sections of oil pipelines together. However, after analyzing the data measured by this device, it is found that the measurement data has a large error because the error transmission coefficient of the measurement value is too large. In order to reduce the error transfer coefficient, a new measuring device for measuring the posture of deep-sea pipelines by a tensioning rope was proposed. Unlike previous measuring devices, this measuring device is based on the positioning of the flange center of the pipe instead of the pin on the outer circle of the pipe. With the comparison of positioning methods between fixing in the center of flange and fixing the outer wall of pipeline, the former can reduce the transition matrix in the process of solving the relative position of the two pipes, and then reduce the magnification of the measurement sensor error. It also reduces two measurement parameters. The solving formula of the position and attitude of the measuring device based on the outer circle positioning of the pipeline is analyzed. It is proved that the error transmission coefficient of the measuring device based on the flange center positioning is smaller. Experiments show that compared with the positioning method based on the outer circle of the pipe, the positioning method based on the flange center has a higher accuracy.
Current Status of Theoretical and Practical Research of Seawater Single-Effect Passive Solar Distillation in Mexico
Authors: Rubio Eduardo , Fernández-Zayas José Luis , Porta-Gándara Miguel A.
Published: February 2020

Solar distillation is a practical alternative for freshwater production in arid zones where seawater is abundant. The attractiveness of this approach resides in the simplicity of the solar still, equipment used to produce saline-free water for drinking, intensive agriculture, domestic use and other purposes. A solar still is an apparatus exposed to solar radiation that consists essentially of a basin with a solar collector where saline water is deposited and covered with a transparent inclined glass plate. The system operates as a greenhouse where the heated seawater evaporates and condensates on the inner surface of the cover. The distillate yield is collected in an external container. A research group in Mexico has been working for years doing research on the process of freshwater production with solar stills. Various research aspects have been addressed, among which are mathematical modeling of the physical phenomenon, practical research by building solar stills with different geometries and sizes, and the proposal of a process for mass-production manufacturing of solar stills with technology innovations. This paper is an overview of some of the most relevant results obtained by these research efforts.
Measuring the Microscopic Structures of Human Dental Enamel Can Predict Caries Experience
Authors: Kelly Ariana M. , Kallistova Anna , Küchler Erika C. , Romanos Helena F. , Lips Andrea , Costa Marcelo C. , Modesto Adriana , Vieira Alexandre R.
Published: February 2020

Objectives: The hierarchical structure of enamel gives insight on the properties of enamel and can influence its strength and ultimately caries experience. Currently, past caries experience is quantified using the decayed, missing, filled teeth/decayed, missing, filled surface (DMFT/DMFS for permanent teeth; dmft/dmfs for primary teeth), or international caries detection and assessment system (ICDAS) scores. By analyzing the structure of enamel, a new measurement can be utilized clinically to predict susceptibility to future caries experience based on a patient’s individual’s biomarkers. The purpose of this study was to test the hypothesis that number of prisms by square millimeter in enamel and average gap distance between prisms and interprismatic areas, influence caries experience through genetic variation of the genes involved in enamel formation. Materials and Methods: Scanning electron microscopy (SEM) images of enamel from primary teeth were used to measure (i) number of prisms by square millimeter and interprismatic spaces, (ii) prism density, and (iii) gap distances between prisms in the enamel samples. The measurements were tested to explore a genetic association with variants of selected genes and correlations with caries experience based on the individual’s DMFT+ dmft score and enamel microhardness at baseline, after an artificial lesion was created and after the artificial lesion was treated with fluoride. Results: Associations were found between variants of genes including ameloblastin, amelogenin, enamelin, tuftelin, tuftelin interactive protein 11, beta defensin 1, matrix metallopeptidase 20 and enamel structure variables measured (number of prisms by square millimeter in enamel and average gap distance between prisms and interprismatic areas). Significant correlations were found between caries experience and microhardness and enamel structure. Negative correlations were found between number of prisms by square millimeter and high caries experience (r value= −0.71), gap distance between prisms and the enamel microhardness after an artificial lesion was created (r value= −0.70), and gap distance between prisms and the enamel microhardness after an artificial lesion was created and then treated with fluoride (r value= −0.81). There was a positive correlation between number of prisms by square millimeter and prism density of the enamel (r value = 0.82). Conclusions: Our data support that genetic variation may impact enamel formation, and therefore influence susceptibility to dental caries and future caries experience. Clinical Relevance: The evaluation of enamel structure that may impact caries experience allows for hypothesizing that the identification of individuals at higher risk for dental caries and implementation of personalized preventative treatments may one day become a reality.
Experimental Biointegration of a Titanium Implant in Delayed Mandibular Reconstruction
Authors: Dolgolev Alexander , Reshetov Igor , Svyatoslavov Dmitry , Sinelnikov Mikhail , Kudrin Konstantin , Dub Vladimir , Put Vladimir , Anikin Vladimir
Published: February 2020

Background: Mandibular reconstruction, after extensive resection of the mandible for the treatment of oral cancer, is a well-known procedure, however, relatively little is known about bone integration into the titanium implant after reconstruction with a temporary plastic implant. The main goal of this experimental study was to study the process of osseous integration into the titanium implant in an in vivo experiment following prior mandibular reconstruction with a temporary plastic implant. Materials and Methods: Four ewes initially underwent a partial one-sided resection of the mandible, with the formation of an approximately 3 × 1 cm defect. All of the subjects received reconstruction with an implantation of a plastic plate (3 cm). The plastic plate was removed and replaced by a titanium implant at 1, 3, 6, and 12 months, accordingly. Both plastic and titanium implants were made via 3D-printing technology and personalized modeling. A total of 6 months after titanium implantation, a histological evaluation of biointegration was performed. Results: All surgeries were uncomplicated. The integration of osseous tissue into the titanium implant was seen in all cases. Histologically, each case showed variable integration of dense fibrotic tissue with fibroblasts and non-mature bone tissue with a definitive layer of bone matrix with many osteoblasts on the periphery. The prior implantation of the plastic plate did not interfere with bone integration into the titanium implant. Conclusion: Preliminary results demonstrated that a temporary plastic implant for mandibular reconstruction does not interfere with the consequent osseous biointegration of a permanent titanium implant. This shows that temporary reconstruction is a safe solution when delayed mandibular reconstruction is required due to disease severity.