bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of pH on the influenza fusion peptide properties unveiled by constant-pH molecular dynamics simulations combined with experiment
Authors: Lousa Diana , Pinto Antónia R. T. , Campos Sara R. R. , Baptista António M. , Veiga Ana S. , Castanho Miguel A. R. B. , Soares Cláudio M. 
Published: November 2020

AbstractThe influenza virus fusion process, whereby the virus fuses its envelope with the host endosome membrane to release the genetic material, takes place in the acidic late endosome environment. Acidification triggers a large conformational change in the fusion protein, hemagglutinin (HA), which enables the insertion of the N-terminal region of the HA2 subunit, known as the fusion peptide, into the membrane of the host endosome. However, the mechanism by which pH modulates the molecular properties of the fusion peptide remains unclear. To answer this question, we performed the first constant-pH molecular dynamics simulations of the influenza fusion peptide in a membrane, extending for 40 µs of aggregated time. The simulations were combined with spectroscopic data, which showed that the peptide is twofold more active in promoting lipid mixing of model membranes at pH 5 than at pH 7.4. The realistic treatment of protonation introduced by the constant-pH molecular dynamics simulations revealed that low pH stabilizes a vertical membrane-spanning conformation and leads to more frequent contacts between the fusion peptide and the lipid headgroups, which may explain the increase in activity. The study also revealed that the N-terminal region is determinant for the peptide’s effect on the membrane.
Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19
Authors: Kuo Tsun-Yung , Lin Meei-Yun , Coffman Robert L. , Campbell John D. , Traquina Paula , Lin Yi-Jiun , Liu Luke Tzu-Chi , Cheng Jinyi , Wu Yu-Chi , Wu Chung-Chin , Tang Wei-Hsuan , Huang Chung-Guei , Tsao Kuo-Chien , Chen Charles 
Published: November 2020

AbstractThe COVID-19 pandemic is a worldwide health emergency which calls for an unprecedented race for vaccines and treatment. In developing a COVID-19 vaccine, we applied technology previously used for MERS-CoV to produce a prefusion-stabilized SARS-CoV-2 spike protein, S-2P. To enhance immunogenicity and mitigate the potential vaccine-induced immunopathology, CpG 1018, a Th1-biasing synthetic toll-like receptor 9 (TLR9) agonist was selected as an adjuvant candidate. S-2P in combination with CpG 1018 and aluminum hydroxide (alum) was found to be the most potent immunogen and induced high titer of neutralizing antibodies in sera of immunized mice against pseudotyped lentivirus reporter or live wild-type SARS-CoV-2. In addition, the antibodies elicited were able to cross-neutralize pseudovirus containing the spike protein of the D614G variant, indicating the potential for broad spectrum protection. A marked Th1 dominant response was noted from cytokines secreted by splenocytes of mice immunized with CpG 1018 and alum. No vaccine-related serious adverse effects were found in the dose-ranging study in rats administered single- or two-dose regimens of S-2P combined with CpG 1018 alone or CpG 1018 with alum. These data support continued development of CHO-derived S-2P formulated with CpG 1018 and alum as a candidate vaccine to prevent COVID-19 disease.
Decreased concentrations of intracellular signaling proteins in colon cancer patients with BRAF mutations
Authors: Olsen Dorte Aa. , Thomsen Caroline E. B. , Andersen Rikke F. , Madsen Jonna S. , Jakobsen Anders , Brandslund Ivan 
Published: November 2020

AbstractThe activation of intracellular signaling pathways plays a critical role in cancer pathogenesis. The current study aims to quantify intracellular signaling proteins in localized colon cancer tissue to investigate the prognostic value of these biomarkers and elucidate their possible relations to mutation status. Colon cancer tissue and autologous reference tissue were collected from 176 patients who underwent colon cancer surgery. Assays were developed to quantify ERK, AKT and cyclin d using single-molecule array technology. KRAS/BRAF/PIK3CA mutation status was determined using droplet digital PCR. Patients with BRAF mutations had decreased concentrations of ERK (p = 0.0003), AKT (p = 0.0001) and cyclin d (p = 0.003), while no significant differences were found between patients with KRAS mutations and wild-type patients. None of the investigated proteins were associated with disease-free survival or overall survival when all patients were included. However, when patients were stratified according to mutation status, significant correlations with overall survival were seen for patients with BRAF mutations and AKT (p = 0.002) or ERK (p = 0.03) and for KRAS mutations and cyclin d (p = 0.01). Conclusions: A strong correlation exists between intracellular signaling protein concentrations and mutational BRAF status. Overall survival in colon cancer patients depends on both gene mutation status and signaling protein concentrations.
Mycobacterial Hsp65 antigen delivered by invasive Lactococcus lactis reduces intestinal inflammation and fibrosis in TNBS-induced chronic colitis model
Authors: da Cunha Vanessa Pecini , Preisser Tatiane Melo , Santana Mariana Passos , Machado Denise Carmona Cara , Pereira Vanessa Bastos , Miyoshi Anderson 
Published: November 2020

AbstractIntestinal fibrosis associated with Crohn’s disease (CD), which a common and serious complication of inflammatory bowel diseases. In this context, heat shock proteins (HSPs) might serve as an alternative treatment because these antigens play important roles in the regulation of effector T cells. We thus evaluated the anti-inflammatory and antifibrotic capacities of an invasive and Hsp65-producing strain—Lactococcus lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65)—in chronic intestinal inflammation to assess its potential as an alternative therapeutic strategy against fibrotic CD. Experimental colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in BALB/c mice, and the mice were treated orally with L. lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65) via intragastric gavage. The oral administration of this strain significantly attenuated the severity of inflammation and intestinal fibrosis in mice (p < 0.05). These results are mainly justified by reductions in the levels of the pro-fibrotic cytokines IL-13 and TGF-β and increases in the concentration of the regulatory cytokine IL-10. The L. lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65) strain contributed to reductions in the severity of inflammatory damage in chronic experimental CD, and these findings confirm the effectiveness of this new antifibrotic strategy based on the delivery of therapeutic proteins to inside cells of the host intestinal mucosa.
SGLT2 inhibition versus sulfonylurea treatment effects on electrolyte and acid–base balance: secondary analysis of a clinical trial reaching glycemic equipoise: Tubular effects of SGLT2 inhibition in Type 2 diabetes
Authors: van Bommel Erik J.M. , Geurts Frank , Muskiet Marcel H.A. , Post Adrian , Bakker Stephan J.L. , Danser A.H. Jan , Touw Daan J. , van Berkel Miranda , Kramer Mark H.H. , Nieuwdorp Max , Ferrannini Ele , Joles Jaap A. , Hoorn Ewout J. , van Raalte Daniël H. 
Published: November 2020

Abstract
Sodium–glucose transporter (SGLT)2 inhibitors increase plasma magnesium and plasma phosphate and may cause ketoacidosis, but the contribution of improved glycemic control to these observations as well as effects on other electrolytes and acid–base parameters remain unknown. Therefore, our objective was to compare the effects of SGLT2 inhibitors dapagliflozin and sulfonylurea gliclazide on plasma electrolytes, urinary electrolyte excretion, and acid–base balance in people with Type 2 diabetes (T2D). We assessed the effects of dapagliflozin and gliclazide treatment on plasma electrolytes and bicarbonate, 24-hour urinary pH and excretions of electrolytes, ammonium, citrate, and sulfate in 44 metformin-treated people with T2D and preserved kidney function. Compared with gliclazide, dapagliflozin increased plasma chloride by 1.4 mmol/l (95% CI 0.4–2.4), plasma magnesium by 0.03 mmol/l (95% CI 0.01–0.06), and plasma sulfate by 0.02 mmol/l (95% CI 0.01–0.04). Compared with baseline, dapagliflozin also significantly increased plasma phosphate, but the same trend was observed with gliclazide. From baseline to week 12, dapagliflozin increased the urinary excretion of citrate by 0.93 ± 1.72 mmol/day, acetoacetate by 48 μmol/day (IQR 17–138), and β-hydroxybutyrate by 59 μmol/day (IQR 0–336), without disturbing acid–base balance. In conclusion, dapagliflozin increases plasma magnesium, chloride, and sulfate compared with gliclazide, while reaching similar glucose-lowering in people with T2D. Dapagliflozin also increases urinary ketone excretion without changing acid–base balance. Therefore, the increase in urinary citrate excretion by dapagliflozin may reflect an effect on cellular metabolism including the tricarboxylic acid cycle. This potentially contributes to kidney protection.
SUPER
Authors: Vietri G. , Mainieri V. , Kakkad D. , Netzer H. , Perna M. , Circosta C. , Harrison C. M. , Zappacosta L. , Husemann B. , Padovani P. , Bischetti M. , Bongiorno A. , Brusa M. , Carniani S. , Cicone C. , Comastri A. , Cresci G. , Feruglio C. , Fiore F. , Lanzuisi G. , Mannucci F. , Marconi A. , Piconcelli E. , Puglisi A. , Salvato M. , Schramm M. , Schulze A. , Scholtz J. , Vignali C. , Zamorani G. 
Published: November 2020

Aims.The SINFONI survey for Unveiling the Physics and Effect of Radiative feedback (SUPER) was designed to conduct a blind search for AGN-driven outflows on X-ray-selected AGNs at redshiftz ∼ 2 with high (∼2 kpc) spatial resolution, and to correlate them with the properties of their host galaxy and central black hole. The main aims of this paper are: (a) to derive reliable estimates for the masses of the black holes and accretion rates for the Type-1 AGNs in this survey; and (b) to characterise the properties of the AGN-driven winds in the broad line region (BLR).Methods.We analysed rest-frame optical and UV spectra of 21 Type-1 AGNs. We used Hα, Hβ, and MgII line profiles to estimate the masses of the black holes. We used the blueshift of the CIV line profile to trace the presence of winds in the BLR.Results.We find that the Hαand Hβline widths are strongly correlated, as is the line continuum luminosity at 5100 Å with Hαline luminosity, resulting in a well-defined correlation between black hole masses estimated from Hαand Hβ. Using these lines, we estimate that the black hole masses for our objects are in the range Log (MBH/M⊙) = 8.4–10.8 and are accreting atλEdd= 0.04–1.3. Furthermore, we confirm the well-known finding that the CIV line width does not correlate with the Balmer lines and the peak of the line profile is blueshifted with respect to the [OIII]-based systemic redshift. These findings support the idea that the CIV line is tracing outflowing gas in the BLR for which we estimated velocities up to ∼4700 km s−1. We confirm the strong dependence of the BLR wind velocity on the UV-to-X-ray continuum slope, the bolometric luminosity, and Eddington ratio. We infer BLR mass outflow rates in the range 0.005–3M⊙yr−1, revealing a correlation with the bolometric luminosity consistent with that observed for ionised winds in the narrow line region (NLR), and X-ray winds detected in local AGNs, and kinetic power ∼10−7 − 10−4 × LBol. The coupling efficiencies predicted by AGN-feedback models are much higher than the values reported for the BLR winds in the SUPER sample; although it should be noted that only a fraction of the energy injected by the AGN into the surrounding medium is expected to become kinetic power in the outflow. Finally, we find an anti-correlation between the equivalent width of the [OIII] line and the CIV velocity shift, and a positive correlation between this latter parameter and [OIII] outflow velocity. These findings, for the first time in an unbiased sample of AGNs atz ∼ 2, support a scenario where BLR winds are connected to galaxy-scale detected outflows, and are therefore capable of affecting the gas in the NLR located at kiloparsec scale distances.
Pour que l’éducation soit au rendez-vous dans l’inclusion scolaire
Authors: de Lajonquière Léandro 
Published: November 2020

L’idée de scolariser des enfants en situation de handicap est le résultat d’un long processus qui, d’une certaine manière, a démarré avec l’éducation de « l’enfant sauvage » de l’Aveyron entreprise par Jean Itard, aux antipodes du nihilisme éducatif exprimé à l’époque par Philippe Pinel. Cependant, notre façon habituelle de concevoir l’inclusion scolaire des enfants dits autistes n’est pas vraiment à la hauteur des nobles intentions éducatives attendues. Nous revenons sur les développements de Maud Mannoni sur la prise en charge institutionnelle des enfants « en situation de handicap » afin de présenter quelques éléments qui mettent en valeur l’enjeu éducatif subjectivant dans tout processus d’inclusion scolaire.
Tränenwegsstenosen im Erwachsenenalter
Authors: Heichel Jens , Struck Hans-Gert 
Published: November 2020

ZusammenfassungZur Aufrechterhaltung der okulären Oberflächenhomöostase und damit den Erhalt der optischen Eigenschaften sind Tränenproduktion, -verteilung und -abtransport essenzielle physiologische Funktionen. Störungen dieser funktionellen Einheit gehen mit starken Beschwerden und einem hohen Leidensdruck bei den Patienten einher. Da etwa 3% unserer Patienten eine Tränenabflussstörung aufweisen, ist die Thematik von hohem klinischem Interesse.
International Comparison of Six Basic eHealth Indicators Across 14 Countries: An eHealth Benchmarking Study
Authors: Ammenwerth Elske , Duftschmid Georg , Al-Hamdan Zaid , Bawadi Hala , Cheung Ngai T. , Cho Kyung-Hee , Goldfarb Guillermo , Gülkesen Kemal H. , Harel Nissim , Kimura Michio , Kırca Önder , Kondoh Hiroshi , Koch Sabine , Lewy Hadas , Mize Dara , Palojoki Sari , Park Hyeoun-Ae , Pearce Christopher , de Quirós Fernan G. B. , Saranto Kaija , Seidel Christoph , Vimarlund Vivian , Were Martin C. , Westbrook Johanna , Wong Chung P. , Haux Reinhold , Lehmann Christoph U. 
Published: November 2020

Abstract
Background Many countries adopt eHealth applications to support patient-centered care. Through information exchange, these eHealth applications may overcome institutional data silos and support holistic and ubiquitous (regional or national) information logistics. Available eHealth indicators mostly describe usage and acceptance of eHealth in a country. The eHealth indicators focusing on the cross-institutional availability of patient-related information for health care professionals, patients, and care givers are rare.
Objectives This study aims to present eHealth indicators on cross-institutional availability of relevant patient data for health care professionals, as well as for patients and their caregivers across 14 countries (Argentina, Australia, Austria, Finland, Germany, Hong Kong as a special administrative region of China, Israel, Japan, Jordan, Kenya, South Korea, Sweden, Turkey, and the United States) to compare our indicators and the resulting data for the examined countries with other eHealth benchmarks and to extend and explore changes to a comparable survey in 2017. We defined “availability of patient data” as the ability to access data in and to add data to the patient record in the respective country.
Methods The invited experts from each of the 14 countries provided the indicator data for their country to reflect the situation on August 1, 2019, as date of reference. Overall, 60 items were aggregated to six eHealth indicators.
Results Availability of patient-related information varies strongly by country. Health care professionals can access patients' most relevant cross-institutional health record data fully in only four countries. Patients and their caregivers can access their health record data fully in only two countries. Patients are able to fully add relevant data only in one country. Finland showed the best outcome of all eHealth indicators, followed by South Korea, Japan, and Sweden.
Conclusion Advancement in eHealth depends on contextual factors such as health care organization, national health politics, privacy laws, and health care financing. Improvements in eHealth indicators are thus often slow. However, our survey shows that some countries were able to improve on at least some indicators between 2017 and 2019. We anticipate further improvements in the future.
Discovery of Comorbid Psychiatric Conditions among Youth Detainees in Juvenile Justice System using Clinical Data
Authors: Islam Humayera , Mosa Abu S. M. , Srivastava Hirsch K. , Mandhadi Vasanthi , Rajendran Dhinakaran , Young-Walker Laine M. 
Published: November 2020

Abstract
Objective The main aim was to analyze the prevalence and patterns of comorbidity in 11 identified broad categories of psychiatric conditions and 48 specific psychiatric conditions among 613 youth from the Missouri Division of Youth Services (DYS) residential sites using advanced data mining techniques on clinical assessment data.
Methods This study was based on youth detainee population at DYS residential placements receiving psychiatric care through the telemedicine network established between DYS and University of Missouri Department of Psychiatry. Association Rule Mining (ARM) algorithm was used to determine the associations and the co-occurrence pattern among the comorbid psychiatric conditions.
Results About 88% of the DYS youth are diagnosed with two or more psychiatric disorders. From the ARM analysis, the most commonly co-occurred disorders are obtained as substance-related or -addicted disorders (SUD) and disruptive, impulse-control, and conduct disorders (CD) (n [%] = 258 [42.1%], followed by SUD, CD, and depressive disorder (DD) (145 [23.7%]), SUD, CD, and neurodevelopmental disorder (NDD) (133 [21.7%]), and DD, CD and NDD (120 [19.6%]).
Discussion The study found high prevalence of comorbidity among the youth patients of the Missouri DYS facilities receiving care through the University of Missouri telemedicine network. The ideal scenario for assessment of any of these disorders in a patient should include substantial consideration in delineating the symptoms and history before eliminating any of them.
Conclusion The comorbid patterns obtained can help in determining treatment regimens for DYS youth that can be effective in reducing recidivism and delinquency.
Microsurgical Reconstruction of the Nose: The Aesthetic Approach to Total Defects
Authors: Pinto Valentina , Antoniazzi Elisa , Contedini Federico , Pignatti Marco , Pizzigallo Angelo , Marchetti Claudio , Cipriani Riccardo 
Published: November 2020

Abstract
Background Reconstruction of complex defects involving nose and close facial units represents an aesthetic and functional challenge. Restoring satisfactory nasal shape, combining aesthetic, nasal function and patent airways is mandatory. In this paper, we describe our approach to total nose defects and we report our 20-year experience in microvascular nose reconstruction.Clinical cases are shown to illustrate different surgical techniques and the evolution of our approach.
Methods Nasal reconstruction procedures were performed on 21 patients between 2000 and 2020 using the radial forearm flap (RFF) or anterolateral thigh (ALT) flap. Reported reconstructions included total/subtotal nasal defects, caused by cancer resections. The key point of our approach is the expanded forehead flap for skin coverage. Reconstruction is completed by cartilage grafts to restore nasal framework and to shape nasal tip. Ancillary procedures were needed in some cases to optimize aesthetic outcomes.
Results Twenty-one patients completed the multistage nasal reconstruction. The RFF flap was used in 56% of the cases (n = 11), while the ALT flap was used in 44% (n = 10) of our case series. No difference has been detected in the number of reconstructive stages required to achieve the final result comparing RFF and ALT reconstruction (3.3 vs. 3.1 reconstructive steps). Ancillary procedures were performed in 7 patients.
Conclusion Microvascular tissue transfer plays a key role in full-thickness nasal defects restoration. Comparing the two groups, both the RFF and ALT are effective and reliable options in lining reconstruction, although with different indications. Expanded forehead flap, combined to free cartilage graft, is our gold standard to provide external skin coverage to rebuild the nasal framework. According to our current approach, accurate preoperative planning, supported by modern technologic tools, multistage reconstruction, and ancillary procedures are useful to accomplish satisfactory functional and aesthetic outcomes.
Bottom-up versus top-down factor investing: an alpha forecasting perspective
Authors: Zurek Martin , Heinrich Lars 
Published: November 2020

AbstractIn a recent discussion about efficient ways to combine multiple firm characteristics into a multifactor portfolio, a distinction was made between the bottom-up and top-down approach. Both approaches integrate characteristics with equal weights and ignore interaction effects from differences in informational content and correlations between the firm characteristics. The authors complement the bottom-up approach for the missing interaction effects by implementing a linear alpha forecasting framework. Bottom-up versus top-down factor investing is typically discussed using the assumption that all characteristics are equally priced, but the pricing impact of different firm characteristics can vary tremendously. The alpha forecasting perspective provides a theoretical motivation for factor investing and helps to compare the bottom-up and top-down approach with regard to the difference of informational content and interaction effects between firm characteristics. Taking into account the difference in informational content between firm characteristics leads to significant performance improvement in factor models with a high concentration of informational content. Equally weighted characteristics result in related performance irrespective of whether the bottom-up or top-down approach is applied.
Historical roots of militarised conservation: the case of Uganda
Authors: Ashaba Ivan 
Published: November 2020

SUMMARY
This briefing engages the militarised conservation literature. Three factors key to understanding present militarised conservation in Uganda are discussed: colonial legacies, the country’s post-colonial history of war and conflict, and the current militarisation under the Museveni government as exemplified in the military collaboration between the Uganda Wildlife Authority and the Uganda Peoples' Defence Forces. It argues that the debate about militarised conservation in today’s Uganda has to be situated within the widening mandate of the military institution under the Museveni government, which came to power through the military path and then gradually militarised significant sections of society more broadly.
Reactivity of bifurcation angle and electroosmosis flow for hemodynamic flow through aortic bifurcation and stenotic wall with heat transfer
Authors: Mekheimer Kh S , Shahzadi Iqra , Nadeem S , Moawad A M A , Zaher A Z 
Published: November 2020

Abstract
The purpose of current research is to illustrate the existence of stenosis on the walls of the aortic artery which are rigid having Y-shape symmetric bifurcation. The non-Newtonian nature of blood is treated under impacts of the electroosmosis forces. In this analysis, a mathematical model is done by specifying the physical problem. Exact solutions are calculated through Mathematica. Graphical configurations are used to discuss the hemodynamics impacts for the concerned parameters. Also, the wall shear stress is studied on the main artery and artery bifurcated. Among of the most important results that the hemodynamic velocity throughout the parent artery is higher than when it moves in the bifurcation channels (arterioles) , a high value is observed for shear stress at outer wall of the arterioles and a comparatively low value of shear stress is observed at the arterioleâ€™s region.